OMEPRAZOLE (Generic Name)
Also called Losectil or Seclo
(Chemical formula: C17H19N3O3S)
About
Omeprazole is used to treat duodenal and benign gastric ulcer (whether associated with Helicobacter pylori or not), gastro-oesophageal reflux disease (GERD), NSAID-associated duodenal or gastric ulcer, gastroduodenal erosions and Zollinger-Ellison syndrome.
Omeprazole is also called Losectil or Seclo.
Omeprazole is a proton-pump inhibitor which inhibits the secretion of gastric juices and works in a similar way to Rabeprazole (Aciphex, Pariet).
It has been found also be effective in conjunction with antibiotics in the treatment of ulcers caused by the bacterium Helicobacter pylori.
Dosages
For healing of GERD – 20mg to be taken once daily for 4-8 weeks.
For benign gastric ulcer - 40mg to be taken daily in the morning for 4-8 weeks.
For long term management of acid-reflux disease take 10mg daily, increasing the dose to 20mg as and when symptoms return.
For duodenal ulcer – 20mg to be taken daily after the morning meal for up to 4 weeks. For maintenance for recurrent cases take 20mg daily. For prevention of relapse take 10mg daily increasing to 20mg daily if symptoms return.
For NSAID associated duodenal or gastric ulcer and gastroduodenal erosions, take 20mg daily for 4-8 weeks. In order to prevent recurrence in individuals continuing to take NSAIDs take 20mg once daily.
For Zollinger-Ellison syndrome – Initially 60mg once daily. However, different individuals respond differently to Rabeprazole and the dose may be adjusted up or down accordingly up to a maximum of 120mg daily, which may be split into two equal doses daily.
For individuals with gastric ulcer and Helicobacter pylori infection – Rabeprazole
is usually combined with antibiotic treatment using two different antibiotics, namely Amoxicillin (1000mg to be taken twice daily for 10 days) and Clarithromycin (500mg to be taken twice daily for 10 days). If you are following this treatment it is very important to take the antibiotics for a full 10 days. After cessation of this combined therapy, take 20mg Omeprazole alone once daily for a further 18 days.
Omeprazole should be taken before eating. They should be taken whole, rather than crushed or chewed. For individuals who have difficulty in swallowing the contents of Omeprazole capsules can be sprinkled on apple sauce and taken that way.
Do not use the combined Omeprazole//Clarimomycin treatment if you are allergic to penicillin or other macrolide antibiotic. (also see separate description for Amoxicillin and Clarithromycin for side effects and precautions for these drugs. Clarithromycin should not be taken by pregnant women.
Omeprazole is not recommended for children (without the supervision of a doctor), nursing mothers or in pregnancy.
Store this medication at 15-300 away from light and moisture.
Side Effects
Omeprazole (Losec) is well tolerated in the vast majority of individuals, both in the short and long term.
The most common side effects are headache (2.4% as opposed to 1.6% in those taking a placebo) nausea, vomiting, abdominal pain, flatulence, diarrhoea, constipation, headache and dizziness.
Less common side effects are dry mouth, insomnia, blurred vision, rash, pruritis, and drowsiness
Also reported: parasthesia, vertigo, alopecia, gynaecomastia, impotence, stomatitis, encephalopathy in severe liver disease, hyponatraemia, reversible agitation, confusion and hallucinations in the severely ill. These side effects are more likely if you take an overdose of Omeprazole.
Rare or very rare side effects are liver dysfunction, peripheral oedema, allergic reactions, photosensitivity, fever, sweating, depression, myalgia, arthralgia, skin eruptions, interstitial nephritis and blood disorders.
If taken with antibiotics, the latter may cause a severe allergic reaction in some individuals (anaphylactic shock). The symptoms of this are difficulty in breathing, increased heart rate, swelling of the tongue and face, panic. If you experience these symptoms seeks medical help immediately
Precautions
Omeprazole should not be used in individuals who are pregnant (may cause foetal defects) or breast feeding without first consulting a doctor.
Do not use if you are suffering from acute hepatic failure.
Not recommended for children.
Omeprazole may decrease the efficacy of ketonazole and atazanavir.
Do not take Omeprazole if you are also taking Clarithromycin with cisapride, primozide, or terfenadine or astemizole.
If taken with antibiotics, the latter may cause a severe allergic reaction in some individuals (anaphylactic shock). The symptoms of this are difficulty in breathing, increased heart rate, swelling of the tongue and face, panic. If you experience these symptoms seeks medical help immediately.
How does it work
Omeprazole is a proton-pump inhibitor which blocks the hydrogen-potassium adenosine triphosphatase enzyme system which acts as a proton pump for gastric parietal cells. It thus inhibits the secretion of gastric juices. Its effects are apparent approximately one hour after administration.
More information
Omeprazole is metabolised in the liver. Approximately 90% is excreted in the urine, and the rest is excreted via the faeces.
Tuesday, August 31, 2010
Ciprofloxacin
Ciprofloxacin
Ciprofloxacin (INN) is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class.[2][3] It is a second-generation fluoroquinolone antibacterial. It kills bacteria by interfering with the enzymes that cause DNA to rewind after being copied, which stops DNA and protein synthesis.
Ciprofloxacin is marketed worldwide with over three hundred different brand names. In the United States, Canada, and the UK, it is marketed as Ciprocin, Ciflox, Ciprox, Cipro-A etc. In addition, ciprofloxacin is available as a generic drug under a variety of different brand names and is also available for limited use in veterinary medicine.
Ciprofloxacin was first patented in 1983 by Bayer A.G. and subsequently approved by the United States Food and Drug Administration (FDA) in 1987. Ciprofloxacin has 12 FDA-approved human uses and other veterinary uses, but it is often used for non-approved uses (off-label). Ciprofloxacin interacts with other drugs, herbal and natural supplements, and thyroid medications.
Availability
Ciprofloxacin is available as:
• tablets (250 mg, 500 mg or 750 mg)
• intravenous solutions (5% and 10%, 100 mL)
• eye and ear drops
In most countries, all formulations require a prescription.
See the latest package insert for ciprofloxacin (Cipro) for additional details.[39]
Mode of action
Ciprofloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. It functions by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV,[40] enzymes necessary to separate bacterial DNA, thereby inhibiting cell division.
This mechanism can also affect mammalian cell replication. In particular, some congeners of this drug family (for example those that contain the C-8 fluorine)[41] display high activity not only against bacterial topoisomerases but also against eukaryotic topoisomerases and are toxic to cultured mammalian cells and in vivo tumor models.[42] Although quinolones are highly toxic to mammalian cells in culture, its mechanism of cytotoxic action is not known. Quinolone induced DNA damage was first reported in 1986 (Hussy et al.).[43]
Recent studies have demonstrated a correlation between mammalian cell cytotoxicity of the quinolones and the induction of micronuclei.[44][45][46][47] As such some fluoroquinolones may cause injury to the chromosome of eukaryotic cells.[48][49][50][51][52][53]
There continues to be debate as to whether or not this DNA damage is to be considered one of the mechanisms of action concerning the severe adverse reactions experienced by some patients following fluoroquinolone therapy.[42][54][55]
Contraindications
As noted above, under licensed use, ciprofloxacin is also now considered to be contraindicated for the treatment of certain sexually transmitted diseases by some experts due to bacterial resistance.[56]
There are only four contraindications found within the 2009 package insert:[39]
• “Coadministration of ciprofloxacin with other drugs primarily metabolized by CYP1A2 results in increased plasma concentrations of these drugs and could lead to clinically significant adverse events of the coadministered drug.”
• “Concomitant administration with tizanidine is contraindicated”
• “Ciprofloxacin is contraindicated in persons with a history of hypersensitivity to ciprofloxacin, any member of the quinolone class of antimicrobial agents, or any of the product components.”
• “Local I.V. site reactions are more frequent if the infusion time is 30 minutes or less. These may appear as local skin reactions that resolve rapidly upon completion of the infusion. Subsequent intravenous administration is not contraindicated unless the reactions recur or worsen.”'
Due to growing prevalence of antibiotic resistance to the fluoroquinolones in southeast Asia, the use of ciprofloxacin in patients having been to southeast Asia is increasingly being discouraged.[57]
Ciprofloxacin is also considered to be contraindicated within the pediatric population (except for the indications outlined under licensed use above), pregnancy, nursing mothers, and in patients with epilepsy or other seizure disorders.
• Pregnancy
The fluoroquinolones rapidly cross the blood-placenta and blood-milk barriers, and are extensively distributed into the fetal tissues. For this reason, the fluoroquinolones are contraindicated during pregnancy due to the risk of spontaneous abortions and birth defects. The fluoroquinolones have also been reported as being present in the mother’s milk and are passed on to the nursing child, which may increases the risk of the child suffering from this syndrome as well, even though the child had never been prescribed or taken any of the drugs found within this class.[58][59]
• Pediatric population
Fluoroquinolones are not licensed by the U.S. FDA for use in children due to the risk of fatalities[60] as well as permanent injury to the musculoskeletal system, with two exceptions. Ciprofloxacin is being licensed for the treatment of complicated urinary tract infections and pyelonephritis due to Escherichia coli, and inhalational anthrax (postexposure), and levofloxacin was recently licensed for the treatment of inhalational anthrax (postexposure). However, the fluoroquinolones are licensed to treat lower respiratory infections in children with cystic fibrosis in the UK.
Within the studies submitted in response to a Pediatric Written Request (Ciprofloxacin, circa 2004), the rate of atrophy was reported to be 9.3%.[61] Within the BPCA Pediatric Studies Summary for ciprofloxacin[61], it was stated that the overall incidence of adverse events at six weeks was 41%. This would be consistent with the safety profile found with the other fluoroquinolones studied in the pediatric population. As such, the current ban on the use of the fluoroquinolones in the pediatric population is both reasonable and supported by various clinical studies. The most recent long term study, BAY 0 9867 Cipro Pediatric Use Study (QUIP), which followed pediatric patients from 1999–2008,[62] supports the current expert opinion that the risk of permanent injury continues to outweigh the potential benefits of ciprofloxacin therapy in the pediatric population.
Within the United States, the FDA has stated it is their intention to pursue the licensing of the fluoroquinolones for pediatric use in spite of the evidence presented at that 62 Meeting of the Anti-Infective Drugs Advisory Committee that the fluoroquinolones cause irreversible joint damage in the pediatric population.[63]
• Depression and anxiety disorders
Ciprofloxacin has highly pronounced side effects in people suffering from panic disorder or/and depression. There have been reported cases of psychosis, suicide attempts, panic attacks and acute anxiety, all occurring during or shortly after ciprofloxacin treatment. Patients with previous or current psychiatric conditions, are prone to experiencing this type of side effect. Caution is highly advised.
Special precautions
The status of the patient’s renal function and hepatic function must also be taken into consideration to avoid an accumulation that may lead to an overdose and the development of toxicity. Ciprofloxacin is eliminated primarily by renal excretion. However, the drug is also metabolized and partially cleared through the liver and the intestine. Modification of the dosage is recommended using the table found within the package insert for those with impaired liver or kidney function. However, since the drug is known to be substantially excreted by the kidneys, the risk of toxic reactions to this drug may be greater in patients with impaired renal function. The duration of treatment depends upon the severity of infection and the usual duration is 7 to 14 days.[24]
Adverse effects
See also: Adverse effects of fluoroquinolones
Serious adverse events occur more commonly with fluoroquinolones than with any other antibiotic drug classes. In most, adverse reactions are mild to moderate; however, occasionally serious adverse effects occur.[64][65] There have been a number of regulatory actions taken as a result of such adverse reactions, which included published warnings,[66][67] additional warnings and safety information added to the package inserts[68] together with the issuance of "Dear Doctor Letters"[69] concerning the recent addition of Black Box Warnings. In 2004, the U.S. FDA requested new warning labels to be added to all of the fluoroquinolones, including ciprofloxacin, regarding peripheral neuropathy (irreversible nerve damage), tendon damage, heart problems (prolonged QT Interval / torsades de pointes), pseudomembranous colitis, rhabdomyolysis (muscle breakdown), Stevens-Johnson syndrome, as well as concurrent usage of NSAIDs contributing to the severity of these reactions.
Subsequent to this, on June 25, 2007, the U.S. FDA required the manufacturer to add an additional warning to the package inserts that stated that “Other serious and sometimes fatal events, some due to hypersensitivity, and some due to uncertain etiology, have been reported in patients receiving therapy with quinolones, including ciprofloxacin.”[70] It was not until 2008, (four years later) that the label revisions for ciprofloxacin included any warnings concerning heart problems (prolonged QT Interval / torsades de pointes). Warnings concerning rhabdomyolysis and Stevens-Johnson syndrome are still conspicuously absent from the package inserts as of September 2009.
The serious adverse effects that may occur as a result of ciprofloxacin therapy include irreversible peripheral neuropathy,[71][72] spontaneous tendon rupture and tendonitis,[73][74][75][76] acute liver failure or serious liver injury (hepatitis),[77][78] QTc prolongation/torsades de pointes,[24] toxic epidermal necrolysis (TEN),[79][80][81] and Stevens-Johnson syndrome, severe central nervous system disorders (CNS)[30] and Clostridium difficile associated disease (CDAD: pseudomembranous colitis),[82][83] as well as photosensitivity/phototoxicity reactions.
Psychotic reactions and confusional states, acute pancreatitis,[84] bone marrow depression, interstitial nephritis and hemolytic anemia may also occur during ciprofloxacin therapy.[85][86] Additional serious adverse reactions include temporary, as well as permanent, loss of vision,[87][88] irreversible double vision,[89] drug induced psychosis[90][91] and chorea (involuntary muscle movements),[92] impaired color vision, exanthema, abdominal pain, malaise, drug fever, dysaesthesia and eosinophilia.[93][94] Pseudotumor cerebri, commonly known as idiopathic intracranial hypertension (IIH), (also referred to as increased intracranial pressure), has been reported to occur as a serious adverse reaction to ciprofloxacin.[95]
Children and the elderly are at a much greater risk of experiencing such adverse reactions.[96][97] Such reactions may manifest during fluoroquinolone therapy, and long after it had been discontinued.[98]
Serious visual complications have also been reported to occur with ophthalmic fluoroquinolone therapy, which may also occur with ciprofloxacin eye drops, especially corneal perforation, but also evisceration and enucleation. This increased incidents of corneal perforation may be due to fluoroquinolones causing alterations in stromal collagen, leading to a reduction in tectonic strength.[99][100] As noted previously permanent double vision (diplopia) has also been reported.[89] An unusual case of seizures has also been reported with ciprofloxacin ear drops in an elderly patient.[101]
Some groups refer to these adverse events as "fluoroquinolone toxicity". These groups of people claim to have suffered serious long term harm to their health from using fluoroquinolones. This has led to a class action lawsuit by people harmed by the use of fluoroquinolones, as well as legal action by the consumer advocate group Public Citizen.[102] Partly as a result of the efforts of the State of Illinois and Public Citizen, the FDA ordered black box warnings on all fluoroquinolones advising consumers of the possible toxic effects of fluoroquinolones on tendons.[103]
Interactions
The toxicity of drugs that are metabolised by the cytochrome P450 system is enhanced by concomitant use of some quinolones. Coadministration may dangerously increase coumarin (warfarin) activity; INR should be monitored closely. They may also interact with the GABA A receptor and cause neurological symptoms; this effect is augmented by certain nonsteroidal anti-inflammatory drugs.[104] Quercetin, a flavonol, occasionally used as a dietary supplement, may interact with fluoroquinolones, as quercetin competitively binds to bacterial DNA gyrase. Some foods, such as garlic and apples, contain high levels of quercetin; whether this inhibits or enhances the effect of fluoroquinolones is not entirely clear.[105] Ciprofloxacin can reduce phenytoin plasma levels, which may, in some cases, result in seizures.[106] Ciprofloxacin may interfere with the levels of thyroid medications resulting in hypothyroidism.[107]
On 9 November 2005, the U.S. FDA required the manufacturers to provide additional warnings within the package inserts concerning ciprofloxacin being an inhibitor of human cytochrome P450 1A2 (CYP1A2) mediated metabolism. The new warning stated:
"Coadministration of ciprofloxacin with other drugs primarily metabolized by CYP1A2 results in increased plasma concentrations of these drugs and could lead to clinically significant adverse events of the coadministered drug."[108]
Concurrent administration of ciprofloxacin with magnesium or aluminum antacids, sucralfate or products containing calcium, iron, or zinc (including multivitamins or other dietary supplements) may substantially decrease the absorption of ciprofloxacin, resulting in serum and urine levels considerably lower than desired.[109]
[edit] Significant drug interactions
Ciprofloxacin can alter and be altered by the metabolism and effects of other drugs, resulting in some significant drug-drug interactions that may affect the musculoskeletal, central nervous, renal, and other systems.
Current or past treatment with oral corticosteroids is associated with an increased risk of achilles tendon rupture, especially in elderly patients who are also taking the fluoroquinolones.[110] This is the subject of Black box warnings in FDA and BNF labeling for quinolones.
The Committee on the Safety of Medicines and the FDA warn that central nervous system adverse effects, including seizure risk, may be increased when NSAIDs are combined with quinolones.[24][111] The interaction between quinolones and NSAIDs is important, because it has the potential for considerable CNS toxicity. The mechanism for this interaction is believed to be due to a synergistic increased antagonism of GABA neurotransmission.[65]
Ciprofloxacin's renal clearance may affect other drugs subject to renal clearance or otherwise affecting the kidney. The use of ciprofloxacin concomitantly with cyclosporine has also been associated with transient elevations in serum creatinine. Renal tubular transport of methotrexate may be inhibited by concomitant administration of ciprofloxacin, potentially leading to increased plasma levels of methotrexate and risk of methotrexate toxicity. Probenecid interferes with renal tubular secretion of ciprofloxacin and produces an increase in the level of ciprofloxacin in serum.[24]
Some quinolones, including ciprofloxacin, exert an inhibitory effect on the cytochrome P-450 enzyme CYP1A2, thereby reducing clearance, and thus increasing blood levels of tizanidine and methylxanthines (e.g., theophylline and caffeine).[112][113] The quinolones have also been reported to enhance the effects of warfarin or its derivatives.[24] Such interactions can augment the effects of the co-administered drug, including adverse effects. Ciprofloxacin can reduce effects of other drugs; for example, it has been shown to interact with thyroid medications (levothyroxine), resulting in unexplained hypothyroidism.[114] Altered serum levels of phenytoin (increased and decreased) have been reported in patients receiving concomitant ciprofloxacin.[24]
Overdose
Overdose of ciprofloxacin may result in reversible renal toxicity. Treatment of overdose includes emptying of the stomach via induced vomiting or by gastric lavage. Careful monitoring and supportive treatment, monitoring of renal function and maintaining adequate hydration is recommended by the manufacturer. Administration of magnesium, aluminum, or calcium containing antacids can reduce the absorption of ciprofloxacin. Hemodialysis or peritoneal dialysis removes only less than 10 percent of ciprofloxacin.[109] Ciprofloxacin may be quantitated in plasma or serum to monitor for drug accumulation in patients with hepatic dysfunction or to confirm a diagnosis of poisoning in acute overdose victims.[115]
Chemistry
Ciprofloxacin is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid. Its empirical formula is C17H18FN3O3 and its molecular weight is 331.4 g/mol. It is a faintly yellowish to light yellow crystalline substance.[109]
Ciprofloxacin hydrochloride (USP) is the monohydrochloride monohydrate salt of ciprofloxacin. It is a faintly yellowish to light yellow crystalline substance with a molecular weight of 385.8 g/mol. Its empirical formula is C17H18FN3O3HCl•H2O.[109]
Pharmacokinetics
The effects of 200–400 mg of ciprofloxacin given intravenously are linear; drug accumulation does not occur when administered at 12 hour intervals. Bioavailability is approximately 70-80%, with no significant first pass effect. IV administration produces a similar serum levels as those achieved with administration of 500 mg administered orally. IV administration over 60 minutes given every 8 hours produces similar serum levels of the drug as 750 mg administered orally every 12 hours.[109] Biotransformation is hepatic. The elimination half life is 4 hours.[24]
Overprescribing and bacterial resistance
See also: Antibiotic abuse and Antibiotic resistance
Ciprofloxacin is commonly used for urinary tract and intestinal infections (traveler's diarrhea) and was once considered a powerful antibiotic of last resort,used to treat especially tenacious infections. Not all physicians agreed with this assessment, as evidenced by its wide spread use to treat minor infections as well as non-approved uses. As a result in recent years many bacteria have developed resistance to this drug, leaving it significantly less effective than it would have been otherwise
Resistance to ciprofloxacin and other fluoroquinolones may evolve rapidly, even during a course of treatment. Numerous pathogens, including Staphylococcus aureus, enterococci, and Streptococcus pyogenes now exhibit resistance worldwide. Widespread veterinary usage of the fluoroquinolones, particularly in Europe, has been implicated.
Fluoroquinolones had become the most commonly prescribed class of antibiotics to adults in 2002.Nearly half (42%) of these prescriptions were for conditions not approved by the FDA, such as acute bronchitis, otitis media, and acute upper respiratory tract infection, according to a study that was supported in part by the Agency for Healthcare Research and Quality.Additionally they are commonly prescribed for medical conditions that are not even bacterial to begin with, such as viral infections, or those to which no proven benefit exist.
Current litigation
Bayer AG A class action had been filed against Bayer AG on behalf of employees of the Brentwood Post Office in Washington, D.C., and workers at the U.S. Capitol, along with employees of American Media, Inc. in Florida and postal workers in general who allege that they have suffered serious adverse effects from taking the antibiotic ciprofloxacin (Cipro) in the aftermath of the anthrax attacks in 2001. The adverse effects included; tendon rupture, seizures, intestinal problems, tendonitis, anxiety, insomnia, muscle aches, depression and meniscus tears. The action alleged that Bayer failed to warn class members of the potential side effects of the drug, thereby violating the Pennsylvania Unfair Trade Practices and Consumer Protection Laws. According to the allegations within the complaint, exposed individuals were not informed of the true safety profile of ciprofloxacin, the high rate of adverse events associated with its use, or the availability of safer and equally effective alternative drugs. The complaint further alleged that, as a result of taking Cipro, many individuals suffered severe and debilitating injuries. The action sought funding for a medical monitoring program and compensatory damages for those workers who have suffered side effects. In 2004, the law firm of Goodell, DeVries, Leech & Dann, LLP were retained as national counsel in this litigation. The class action was defeated and the litigation abandoned by the plaintiffs.A similar action had been filed in New Jersey that covers New Jersey postal workers. Final disposition of that lawsuit is unknown. Following the addition of the Black Box Warning in 2008, regarding tendon damage, a significant number of product liability law firms began soliciting clients who have suffered a spontaneous tendon rupture following fluoroquinolone therapy.
Ciprofloxacin (INN) is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class.[2][3] It is a second-generation fluoroquinolone antibacterial. It kills bacteria by interfering with the enzymes that cause DNA to rewind after being copied, which stops DNA and protein synthesis.
Ciprofloxacin is marketed worldwide with over three hundred different brand names. In the United States, Canada, and the UK, it is marketed as Ciprocin, Ciflox, Ciprox, Cipro-A etc. In addition, ciprofloxacin is available as a generic drug under a variety of different brand names and is also available for limited use in veterinary medicine.
Ciprofloxacin was first patented in 1983 by Bayer A.G. and subsequently approved by the United States Food and Drug Administration (FDA) in 1987. Ciprofloxacin has 12 FDA-approved human uses and other veterinary uses, but it is often used for non-approved uses (off-label). Ciprofloxacin interacts with other drugs, herbal and natural supplements, and thyroid medications.
Availability
Ciprofloxacin is available as:
• tablets (250 mg, 500 mg or 750 mg)
• intravenous solutions (5% and 10%, 100 mL)
• eye and ear drops
In most countries, all formulations require a prescription.
See the latest package insert for ciprofloxacin (Cipro) for additional details.[39]
Mode of action
Ciprofloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. It functions by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV,[40] enzymes necessary to separate bacterial DNA, thereby inhibiting cell division.
This mechanism can also affect mammalian cell replication. In particular, some congeners of this drug family (for example those that contain the C-8 fluorine)[41] display high activity not only against bacterial topoisomerases but also against eukaryotic topoisomerases and are toxic to cultured mammalian cells and in vivo tumor models.[42] Although quinolones are highly toxic to mammalian cells in culture, its mechanism of cytotoxic action is not known. Quinolone induced DNA damage was first reported in 1986 (Hussy et al.).[43]
Recent studies have demonstrated a correlation between mammalian cell cytotoxicity of the quinolones and the induction of micronuclei.[44][45][46][47] As such some fluoroquinolones may cause injury to the chromosome of eukaryotic cells.[48][49][50][51][52][53]
There continues to be debate as to whether or not this DNA damage is to be considered one of the mechanisms of action concerning the severe adverse reactions experienced by some patients following fluoroquinolone therapy.[42][54][55]
Contraindications
As noted above, under licensed use, ciprofloxacin is also now considered to be contraindicated for the treatment of certain sexually transmitted diseases by some experts due to bacterial resistance.[56]
There are only four contraindications found within the 2009 package insert:[39]
• “Coadministration of ciprofloxacin with other drugs primarily metabolized by CYP1A2 results in increased plasma concentrations of these drugs and could lead to clinically significant adverse events of the coadministered drug.”
• “Concomitant administration with tizanidine is contraindicated”
• “Ciprofloxacin is contraindicated in persons with a history of hypersensitivity to ciprofloxacin, any member of the quinolone class of antimicrobial agents, or any of the product components.”
• “Local I.V. site reactions are more frequent if the infusion time is 30 minutes or less. These may appear as local skin reactions that resolve rapidly upon completion of the infusion. Subsequent intravenous administration is not contraindicated unless the reactions recur or worsen.”'
Due to growing prevalence of antibiotic resistance to the fluoroquinolones in southeast Asia, the use of ciprofloxacin in patients having been to southeast Asia is increasingly being discouraged.[57]
Ciprofloxacin is also considered to be contraindicated within the pediatric population (except for the indications outlined under licensed use above), pregnancy, nursing mothers, and in patients with epilepsy or other seizure disorders.
• Pregnancy
The fluoroquinolones rapidly cross the blood-placenta and blood-milk barriers, and are extensively distributed into the fetal tissues. For this reason, the fluoroquinolones are contraindicated during pregnancy due to the risk of spontaneous abortions and birth defects. The fluoroquinolones have also been reported as being present in the mother’s milk and are passed on to the nursing child, which may increases the risk of the child suffering from this syndrome as well, even though the child had never been prescribed or taken any of the drugs found within this class.[58][59]
• Pediatric population
Fluoroquinolones are not licensed by the U.S. FDA for use in children due to the risk of fatalities[60] as well as permanent injury to the musculoskeletal system, with two exceptions. Ciprofloxacin is being licensed for the treatment of complicated urinary tract infections and pyelonephritis due to Escherichia coli, and inhalational anthrax (postexposure), and levofloxacin was recently licensed for the treatment of inhalational anthrax (postexposure). However, the fluoroquinolones are licensed to treat lower respiratory infections in children with cystic fibrosis in the UK.
Within the studies submitted in response to a Pediatric Written Request (Ciprofloxacin, circa 2004), the rate of atrophy was reported to be 9.3%.[61] Within the BPCA Pediatric Studies Summary for ciprofloxacin[61], it was stated that the overall incidence of adverse events at six weeks was 41%. This would be consistent with the safety profile found with the other fluoroquinolones studied in the pediatric population. As such, the current ban on the use of the fluoroquinolones in the pediatric population is both reasonable and supported by various clinical studies. The most recent long term study, BAY 0 9867 Cipro Pediatric Use Study (QUIP), which followed pediatric patients from 1999–2008,[62] supports the current expert opinion that the risk of permanent injury continues to outweigh the potential benefits of ciprofloxacin therapy in the pediatric population.
Within the United States, the FDA has stated it is their intention to pursue the licensing of the fluoroquinolones for pediatric use in spite of the evidence presented at that 62 Meeting of the Anti-Infective Drugs Advisory Committee that the fluoroquinolones cause irreversible joint damage in the pediatric population.[63]
• Depression and anxiety disorders
Ciprofloxacin has highly pronounced side effects in people suffering from panic disorder or/and depression. There have been reported cases of psychosis, suicide attempts, panic attacks and acute anxiety, all occurring during or shortly after ciprofloxacin treatment. Patients with previous or current psychiatric conditions, are prone to experiencing this type of side effect. Caution is highly advised.
Special precautions
The status of the patient’s renal function and hepatic function must also be taken into consideration to avoid an accumulation that may lead to an overdose and the development of toxicity. Ciprofloxacin is eliminated primarily by renal excretion. However, the drug is also metabolized and partially cleared through the liver and the intestine. Modification of the dosage is recommended using the table found within the package insert for those with impaired liver or kidney function. However, since the drug is known to be substantially excreted by the kidneys, the risk of toxic reactions to this drug may be greater in patients with impaired renal function. The duration of treatment depends upon the severity of infection and the usual duration is 7 to 14 days.[24]
Adverse effects
See also: Adverse effects of fluoroquinolones
Serious adverse events occur more commonly with fluoroquinolones than with any other antibiotic drug classes. In most, adverse reactions are mild to moderate; however, occasionally serious adverse effects occur.[64][65] There have been a number of regulatory actions taken as a result of such adverse reactions, which included published warnings,[66][67] additional warnings and safety information added to the package inserts[68] together with the issuance of "Dear Doctor Letters"[69] concerning the recent addition of Black Box Warnings. In 2004, the U.S. FDA requested new warning labels to be added to all of the fluoroquinolones, including ciprofloxacin, regarding peripheral neuropathy (irreversible nerve damage), tendon damage, heart problems (prolonged QT Interval / torsades de pointes), pseudomembranous colitis, rhabdomyolysis (muscle breakdown), Stevens-Johnson syndrome, as well as concurrent usage of NSAIDs contributing to the severity of these reactions.
Subsequent to this, on June 25, 2007, the U.S. FDA required the manufacturer to add an additional warning to the package inserts that stated that “Other serious and sometimes fatal events, some due to hypersensitivity, and some due to uncertain etiology, have been reported in patients receiving therapy with quinolones, including ciprofloxacin.”[70] It was not until 2008, (four years later) that the label revisions for ciprofloxacin included any warnings concerning heart problems (prolonged QT Interval / torsades de pointes). Warnings concerning rhabdomyolysis and Stevens-Johnson syndrome are still conspicuously absent from the package inserts as of September 2009.
The serious adverse effects that may occur as a result of ciprofloxacin therapy include irreversible peripheral neuropathy,[71][72] spontaneous tendon rupture and tendonitis,[73][74][75][76] acute liver failure or serious liver injury (hepatitis),[77][78] QTc prolongation/torsades de pointes,[24] toxic epidermal necrolysis (TEN),[79][80][81] and Stevens-Johnson syndrome, severe central nervous system disorders (CNS)[30] and Clostridium difficile associated disease (CDAD: pseudomembranous colitis),[82][83] as well as photosensitivity/phototoxicity reactions.
Psychotic reactions and confusional states, acute pancreatitis,[84] bone marrow depression, interstitial nephritis and hemolytic anemia may also occur during ciprofloxacin therapy.[85][86] Additional serious adverse reactions include temporary, as well as permanent, loss of vision,[87][88] irreversible double vision,[89] drug induced psychosis[90][91] and chorea (involuntary muscle movements),[92] impaired color vision, exanthema, abdominal pain, malaise, drug fever, dysaesthesia and eosinophilia.[93][94] Pseudotumor cerebri, commonly known as idiopathic intracranial hypertension (IIH), (also referred to as increased intracranial pressure), has been reported to occur as a serious adverse reaction to ciprofloxacin.[95]
Children and the elderly are at a much greater risk of experiencing such adverse reactions.[96][97] Such reactions may manifest during fluoroquinolone therapy, and long after it had been discontinued.[98]
Serious visual complications have also been reported to occur with ophthalmic fluoroquinolone therapy, which may also occur with ciprofloxacin eye drops, especially corneal perforation, but also evisceration and enucleation. This increased incidents of corneal perforation may be due to fluoroquinolones causing alterations in stromal collagen, leading to a reduction in tectonic strength.[99][100] As noted previously permanent double vision (diplopia) has also been reported.[89] An unusual case of seizures has also been reported with ciprofloxacin ear drops in an elderly patient.[101]
Some groups refer to these adverse events as "fluoroquinolone toxicity". These groups of people claim to have suffered serious long term harm to their health from using fluoroquinolones. This has led to a class action lawsuit by people harmed by the use of fluoroquinolones, as well as legal action by the consumer advocate group Public Citizen.[102] Partly as a result of the efforts of the State of Illinois and Public Citizen, the FDA ordered black box warnings on all fluoroquinolones advising consumers of the possible toxic effects of fluoroquinolones on tendons.[103]
Interactions
The toxicity of drugs that are metabolised by the cytochrome P450 system is enhanced by concomitant use of some quinolones. Coadministration may dangerously increase coumarin (warfarin) activity; INR should be monitored closely. They may also interact with the GABA A receptor and cause neurological symptoms; this effect is augmented by certain nonsteroidal anti-inflammatory drugs.[104] Quercetin, a flavonol, occasionally used as a dietary supplement, may interact with fluoroquinolones, as quercetin competitively binds to bacterial DNA gyrase. Some foods, such as garlic and apples, contain high levels of quercetin; whether this inhibits or enhances the effect of fluoroquinolones is not entirely clear.[105] Ciprofloxacin can reduce phenytoin plasma levels, which may, in some cases, result in seizures.[106] Ciprofloxacin may interfere with the levels of thyroid medications resulting in hypothyroidism.[107]
On 9 November 2005, the U.S. FDA required the manufacturers to provide additional warnings within the package inserts concerning ciprofloxacin being an inhibitor of human cytochrome P450 1A2 (CYP1A2) mediated metabolism. The new warning stated:
"Coadministration of ciprofloxacin with other drugs primarily metabolized by CYP1A2 results in increased plasma concentrations of these drugs and could lead to clinically significant adverse events of the coadministered drug."[108]
Concurrent administration of ciprofloxacin with magnesium or aluminum antacids, sucralfate or products containing calcium, iron, or zinc (including multivitamins or other dietary supplements) may substantially decrease the absorption of ciprofloxacin, resulting in serum and urine levels considerably lower than desired.[109]
[edit] Significant drug interactions
Ciprofloxacin can alter and be altered by the metabolism and effects of other drugs, resulting in some significant drug-drug interactions that may affect the musculoskeletal, central nervous, renal, and other systems.
Current or past treatment with oral corticosteroids is associated with an increased risk of achilles tendon rupture, especially in elderly patients who are also taking the fluoroquinolones.[110] This is the subject of Black box warnings in FDA and BNF labeling for quinolones.
The Committee on the Safety of Medicines and the FDA warn that central nervous system adverse effects, including seizure risk, may be increased when NSAIDs are combined with quinolones.[24][111] The interaction between quinolones and NSAIDs is important, because it has the potential for considerable CNS toxicity. The mechanism for this interaction is believed to be due to a synergistic increased antagonism of GABA neurotransmission.[65]
Ciprofloxacin's renal clearance may affect other drugs subject to renal clearance or otherwise affecting the kidney. The use of ciprofloxacin concomitantly with cyclosporine has also been associated with transient elevations in serum creatinine. Renal tubular transport of methotrexate may be inhibited by concomitant administration of ciprofloxacin, potentially leading to increased plasma levels of methotrexate and risk of methotrexate toxicity. Probenecid interferes with renal tubular secretion of ciprofloxacin and produces an increase in the level of ciprofloxacin in serum.[24]
Some quinolones, including ciprofloxacin, exert an inhibitory effect on the cytochrome P-450 enzyme CYP1A2, thereby reducing clearance, and thus increasing blood levels of tizanidine and methylxanthines (e.g., theophylline and caffeine).[112][113] The quinolones have also been reported to enhance the effects of warfarin or its derivatives.[24] Such interactions can augment the effects of the co-administered drug, including adverse effects. Ciprofloxacin can reduce effects of other drugs; for example, it has been shown to interact with thyroid medications (levothyroxine), resulting in unexplained hypothyroidism.[114] Altered serum levels of phenytoin (increased and decreased) have been reported in patients receiving concomitant ciprofloxacin.[24]
Overdose
Overdose of ciprofloxacin may result in reversible renal toxicity. Treatment of overdose includes emptying of the stomach via induced vomiting or by gastric lavage. Careful monitoring and supportive treatment, monitoring of renal function and maintaining adequate hydration is recommended by the manufacturer. Administration of magnesium, aluminum, or calcium containing antacids can reduce the absorption of ciprofloxacin. Hemodialysis or peritoneal dialysis removes only less than 10 percent of ciprofloxacin.[109] Ciprofloxacin may be quantitated in plasma or serum to monitor for drug accumulation in patients with hepatic dysfunction or to confirm a diagnosis of poisoning in acute overdose victims.[115]
Chemistry
Ciprofloxacin is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid. Its empirical formula is C17H18FN3O3 and its molecular weight is 331.4 g/mol. It is a faintly yellowish to light yellow crystalline substance.[109]
Ciprofloxacin hydrochloride (USP) is the monohydrochloride monohydrate salt of ciprofloxacin. It is a faintly yellowish to light yellow crystalline substance with a molecular weight of 385.8 g/mol. Its empirical formula is C17H18FN3O3HCl•H2O.[109]
Pharmacokinetics
The effects of 200–400 mg of ciprofloxacin given intravenously are linear; drug accumulation does not occur when administered at 12 hour intervals. Bioavailability is approximately 70-80%, with no significant first pass effect. IV administration produces a similar serum levels as those achieved with administration of 500 mg administered orally. IV administration over 60 minutes given every 8 hours produces similar serum levels of the drug as 750 mg administered orally every 12 hours.[109] Biotransformation is hepatic. The elimination half life is 4 hours.[24]
Overprescribing and bacterial resistance
See also: Antibiotic abuse and Antibiotic resistance
Ciprofloxacin is commonly used for urinary tract and intestinal infections (traveler's diarrhea) and was once considered a powerful antibiotic of last resort,used to treat especially tenacious infections. Not all physicians agreed with this assessment, as evidenced by its wide spread use to treat minor infections as well as non-approved uses. As a result in recent years many bacteria have developed resistance to this drug, leaving it significantly less effective than it would have been otherwise
Resistance to ciprofloxacin and other fluoroquinolones may evolve rapidly, even during a course of treatment. Numerous pathogens, including Staphylococcus aureus, enterococci, and Streptococcus pyogenes now exhibit resistance worldwide. Widespread veterinary usage of the fluoroquinolones, particularly in Europe, has been implicated.
Fluoroquinolones had become the most commonly prescribed class of antibiotics to adults in 2002.Nearly half (42%) of these prescriptions were for conditions not approved by the FDA, such as acute bronchitis, otitis media, and acute upper respiratory tract infection, according to a study that was supported in part by the Agency for Healthcare Research and Quality.Additionally they are commonly prescribed for medical conditions that are not even bacterial to begin with, such as viral infections, or those to which no proven benefit exist.
Current litigation
Bayer AG A class action had been filed against Bayer AG on behalf of employees of the Brentwood Post Office in Washington, D.C., and workers at the U.S. Capitol, along with employees of American Media, Inc. in Florida and postal workers in general who allege that they have suffered serious adverse effects from taking the antibiotic ciprofloxacin (Cipro) in the aftermath of the anthrax attacks in 2001. The adverse effects included; tendon rupture, seizures, intestinal problems, tendonitis, anxiety, insomnia, muscle aches, depression and meniscus tears. The action alleged that Bayer failed to warn class members of the potential side effects of the drug, thereby violating the Pennsylvania Unfair Trade Practices and Consumer Protection Laws. According to the allegations within the complaint, exposed individuals were not informed of the true safety profile of ciprofloxacin, the high rate of adverse events associated with its use, or the availability of safer and equally effective alternative drugs. The complaint further alleged that, as a result of taking Cipro, many individuals suffered severe and debilitating injuries. The action sought funding for a medical monitoring program and compensatory damages for those workers who have suffered side effects. In 2004, the law firm of Goodell, DeVries, Leech & Dann, LLP were retained as national counsel in this litigation. The class action was defeated and the litigation abandoned by the plaintiffs.A similar action had been filed in New Jersey that covers New Jersey postal workers. Final disposition of that lawsuit is unknown. Following the addition of the Black Box Warning in 2008, regarding tendon damage, a significant number of product liability law firms began soliciting clients who have suffered a spontaneous tendon rupture following fluoroquinolone therapy.
Aceclofenac (Anti-Inflammatory Drug)
The pain management is always a problem for a physician and the search for a safe and effective option is still on.
Although cyclooxygenase-2 selective inhibitors (coxibs) represent a new class of analgesic and anti-inflammatory drugs that exhibits preference for inhibition of cyclooxygenase-2, its cardiovascular safety is controversial, since trial showed increased incidence of cardiovascular events in patients receiving coxibs. There is a need of a drug, which has high efficacy like traditional NSAIDs, shows high GI tolerability like selective cox-2 inhibitors but have no adverse cardiovascular effects.
Aceclofenac has been shown to have potent analgesic and anti-inflammatory activities, similar to indomethacin and diclofenac and due to its preferential cox-2 blockade it has better safety than conventional NSAIDs with respect to adverse effects on gastrointestinal and cardiovascular system.
INTRODUCTION
The pain is symptomatic of some form of dysfunction and resultant inflammatory processes in the body. A survey conducted for the WHO reported that one adult in five suffers from chronic non-malignant pain, which mostly occurs in the back, head, joints and limbs. More than 15% of the worldwide population suffers for instance from some form of osteoarthritis, and this incidence is even higher in the elderly. As the world population is grows older, this incidence will continue to rise.
The pain has been defined as a characteristic sensation arising from a noxious stimulus, which includes its neurophysiological aspect. Sherrington, in his classic definition has further included the reactive component of pain, i.e. the "psychical adjuvant of an imperative protective reflex". This indicates that pain also has a survival value for the species. There are two main classes of pain superficial and deep. Some pain receptors in the body are probably chemoreceptors, as a wide variety of compounds, including autacoids like bradykinin, and several of the prostaglandins, can elicit the pain. Drugs can alter the pain experience in three ways (Pain reception, perception, and reaction) the first that can be intercepted is peripheral pain reception at the nerve endings. This modality is susceptible to non-narcotic analgesic and local anesthesia. The second step, which can be modified, is pain perception at the level of the CNS. Both, narcotic and non-narcotic analgesics interfere with this level of pain integration. The third step, which can be influenced, is pain reaction.
Mechanism of pain & Inflammation:
Prostaglandins are implicated in the inflammatory response and are sensitizing nociceptors to the actions of other Mediators, occurring during acute and chronic inflammatory illness, prostaglandins are produced at the site of inflammation where it is believed that they mediate many of symptoms of inflammation such as oedema and pain.
Arachidonic acid is released from cell membranes by phospholipases, cyclooxygenases catalyze the addition of molecular oxygen to arachidonic acid to form in initially the endoperoxide intermediate prostaglandin G2. The same enzymes also process peroxidase activity, which catalyzes the reduction of these prostaglandins to form PGH2. PGH 2 may then react with a number of enzymes sometimes called isomerases to become one of the prostaglandins or thromboxanes.
Role of Non-Steroidal Anti inflammatory drugs in pain (NSAIDs)
Orally administered NSAIDS play an important role in symptomatic management of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis and other acute pain conditions. In general, they produce their anti-inflammatory and analgesic effects by inhibiting cyclooxygenase and this preventing the production of prostaglandins from arachidonic acid. It has been suggested that some NSAIDS inhibit leukotriene production via lipooxygenase inhibition.
ACECLOFENAC
Aceclofenac is an orally administered phenyl acetic acid derivatives with effects on a variety of inflammatory mediators.
Aceclofenac contains not less than 99.0% and not more than the equivalent of 101.0 percent of 2-[[2-[2-[(2, 6-dichlorophenyl) amino] phenyl] acetyl] oxy] acetic acid.
It is a white or almost white crystalline powder. It is an effective analgesic and anti-inflammatory agent with a good tolerability profile. Through its analgesic and anti-inflammatory properties, aceclofenac provides symptomatic relief in a variety of painful conditions. A reduction in the stimulated generation of reactive oxygen species (O2), which may play a role in joint damage, was observed after 15 days in these patients, but after 180 days. At day 180, O2 release was similar to that seen in a group of 41 healthy untreated individuals.
Structure Activity Relationship
Structure-activity relationship in this series, have not been extensively studied. It does appear that the function of the two o-chloro groups is to force the anilino-phenyl ring out of the plane of the phenylacetic acid portion, this twisting effect being important in the binding of NSAIDs to the active site of the cyclooxygenase enzyme.
Pharmacology
The mode of action of aceclofenac is largely based on the inhibition of prostaglandin synthesis. Aceclofenac is a potent inhibitor of the enzyme cyclooxygenase, which is involved in the production of prostaglandins.
The Drugs inhibits synthesis of the inflammatory cytokines interleukin (IL)-1 and tumor necrosis factor and prostaglandin E2 (PGE2) production. Effects on cell adhesion molecular from neurophils have also been noted. In vitro data indicate inhibition of cyclooxygenase (Cox)-1 and 2 by aceclofenac in whole blood assays, with selectivity for Cox-2 being evident.
Aceclofenac has shown stimulatory effects on cartilage matrix synthesis that may be linked to the ability of the drug to inhibit IL-1 activity. In vitro data indicate stimulation by the drug of synthesis of glycosaminoglycan in osteoarthritic cartilage. There is also evidence that aceclofenac stimulates the synthesis of IL-1 receptor antagonist in human articular chondrocytes subjected to inflammatory stimuli and that 4'-hydroxyacelofenac has chondroprotective properties attributable to suppression of IL-1 mediated promatrix metalloproteinase production and proteoglycan release.
In patients with osteoarthritis of the knee, aceclofenac decrease pain reduces disease severity and improves the functional capacity of the knee. It reduces joint inflammation, pain intensity and the duration of morning stiffness in patients with rheumatoid arthritis. The duration of morning stiffness and pain intensity are reduced and spinal mobility improved, by aceclofenac in patients with ankylosing spondylitis.
PHARMACOKINETICS
Aceclofenac is rapidly and completely absorbed after oral administration, peak plasma concentrations are reached 1 to 3 hours after an oral dose. The drug is highly protein bound (7.99%). The presence of food does alter the extent of absorption of aceclofenac but the absorption rate is reduced. The plasma concentration of aceclofenac was approximately twice that in synovial fluid after multiple doses of the drug in-patient with knee pain and synovial fluid effusion. Aceclofenac is metabolized to a major metabolite, 4'-hydroxyaceclofenac and to a number of other metabolites including 5-hydroxyaceclofenac, 4'-hydroxydiclofenac, diclofenac and 5-hydroxydiclofenac. Renal excretion is the main route of elimination of aceclofenac with 70 to 80% of an administered dose found in the urine, mainly as the glucuronides of aceclofenac and its metabolites of each dose of aceclofenac, 20% is excreted in the faeces. The plasma elimination half-life of the drug is approximately 4 hours.
Drug Interactions
Aceclofenac may increase plasma concentrations of lithium, digoxin and methotrexate, increase the activity of anticoagulant, inhibits the activity of diuretics, enhance cyclosporin nephrotoxicity and precipitate convulsions when co-administered with quinolone antibiotics. Furthermore, hypo or hyperglycaemia may result from the concomitant administration of aceclofenac and antidiabetic drugs, although this is rare. The co administration of aceclofenac with other NSAIDS of corticosteroids may results in increased frequency of adverse event.
Adverse Drug Reaction
Aceclofenac is well tolerated, with most adverse events being minor and reversible and affecting mainly the GI system. Most common events include dyspepsia (7.5%), abdominal pain (6.2%), nausea (1.5%), diarrhea (1.5%), flatulence (0.8%), gastritis (0.6%), constipation (0.5%), vomiting (0.5%), ulcerative stomatitis (0.1%), pancreatitis (0.1%).
Although the incidence of gastro intestinal adverse events with aceclofenac was similar to those of comparator NSAIDS in individual clinical trials, withdrawal rates due to these events were significantly lower aceclofenac than with ketoprofen and tenoxicam.
Other adverse effect, which is not common such as dizziness (1%), vertigo (0.3%), and rare cases: par aesthesia and tremor.
Dosage and Administration
The usual dose of aceclofenac is 100 mg given twice daily by mouth, one tablet in the morning and one in the evening. There is no evidence that the dosage of aceclofenac needs to be modified in patients with mild renal impairment, but as with other NSAIDS caution should be exercised.
Aceclofenac Balanced Cox Inhibitor
It has been suggested that aceclofenac blocks PGE2 production via cyclo-oxygenase (cox)-1 and cox-2 inhibition after intracellular metabolism to 4'-hydroxyaceclofenac and diclofenac in human rheumatoid synovial and other inflammatory cells.
However data from human whole blood assays show inhibition of cox-2 (with minimal effects on cox-1) by both the parent compound and 4'-hydroxyaceclofenac. IC50 values of cox-1 and cox-2 respectively were > 100 and 0.8 for aceclofenac and > 100 and 36 for 4'-hydroxyaceclofenac.
IC 50
Cox-1 Cox-2
Aceclofenac > 100 0.8
4'-hydroxyaceclofenac > 100 36
Further evidence of cox-2 selectivity of aceclofenac has been shown by an IC50 ratio (cox-2: cox-1) of 0.26, which fell between IC50 ratios of 0.7 and 0.12 for the cox-2 inhibitors celecoxib and rofecoxib, respectively in other study. Most recent data have shown aceclofenac to have the highest cox-1: cox-2 IC 50 ratio of a range of agents, including rofecoxib, celecoxib, nimesulide, diclofenac and tenoxicam.
Drugs IC50
Aceclofenac 0.26
Celecoxib 0.7
Rofecoxib 0.12
Aceclofenac may prevent the degradation of articular connective tissue in patients with rheumatoid arthritis and osteoarthritis and this should be classified as unique NSAIDs.
Aceclofenac - Clinical Efficacy
In large trials of 2 to 6 months duration, aceclofenac significantly reduced pain and improves functional capacity and mobility relative to baseline in patients with osteoarthritis, rheumatoid arthritis or ankylosing spondylitis and reduces inflammation in patients with rheumatoid arthritis. No head to head comparison between aceclofenac and coxibs have been performed, nor for efficacy neither for tolerance.
Aceclofenac in osteoarthritis
In patients with osteoarthritis of the knee, aceclofenac decreases pain, reduces disease severity and improves the functional capacity of the knee to a similar extent to diclofenac, piroxicam, and naproxen.
Aceclofenac in rheumatoid arthritis
The anti-inflammatory and analgesic efficacy of aceclofenac is similar to that of ketoprofen, indomethacin, tenoxicam and diclofenac in patients with rheumatoid arthritis. In randomized, double blind trials in 169 to 261 patients, aceclofenac (100 mg twice daily for 3 or 6 months) significantly reduced relative to baseline joint inflammation, pain intensity and the duration of morning stiffness and improved handgrip strength.
Aceclofenac in ankylosing spondylitis
The duration of morning stiffness and pain intensity are reduced and spinal mobility improved, by aceclofenac in patients with ankylosing spondylitis, with improvements being similar to those observed with indomethacin, naproxen or tenoxicam. These effects were observed after aceclofenac 100 mg twice daily for 3 months in randomized, double blind trials involving 104 to 308 patients.
Aceclofenac in dental pain
The analgesic efficacy as single doses of aceclofenac has been assessed in patients with moderate to severe tooth pain and in extraction of impacted third molars. The analgesic efficacy of single doses of aceclofenac 50, 100 and 150 mg was greater than that of placebo in patients with moderate to severe tooth pain or pain caused by extraction of impacted third molars.
Aceclofenac in postoperative pain
The analgesic efficacy of aceclofenac has been shown in comparisons with paracetamol in women undergoing episiotomy. Aceclofenac 100 mg was superior to paracetamol 650 mg in providing relief from postepisiotomy pain, particularly 3 to 5 hours after ingestion.
Aceclofenac in Dysmenorrhoea
In a more recent noncomparative study in 1338 women with dysmenorrohea treated for first 3 days of 2 consecutive cycles.
Aceclofenac in acute lumbago
Aceclofenac (150 mg intramuscularly for 2 days, then 100 mg orally, both twice daily) was superior to diclofenac in alleviating functional impairment in a 7 days study in 100 patients with acute lumbago. Aceclofenac 100 mg twice daily was associated with symptomatic relief of acute low back pain in a non-comparative study in 67 pateints.
Aceclofenac in musculoskeletal trauma
Aceclofenac 100 mg twice daily has also been assessed in patients with musculoskeletal trauma, although only non-comparative studies are available.
Aceclofenac Gonalgia (Knee pain)
A controlled double blind study was performed with aceclofenac comparing it with diclofenac in 40 patients with acute or chronic gonalgia. The results of the trial indicate slightly superior activity, although there was no statistically significant difference between two drugs.
CONCLUSION
Aceclofenac is superior form other NSAIDs as it has selectivity for cox-2, a beneficial cox inhibitor, well tolerated, better GI tolerability and improved cardiovascular safety when compared to other selective cox-2 inhibitors. It also shows Increased matrix component synthesis and protection of chondrocytes against apoptosis. Aceclofenac has a faster and more potent effect than the other NSAIDs. It efficiently interferes with Neutrophils adhesion to endothelium and this effect may represent an additional relevant mechanism in its anti-inflammatory activity. Aceclofenac has an outstanding anti-inflammatory profile, involving a classical inhibition of prostaglandins E2, a decrease in the expression of several cytokines including interleukin and tumor necrosis factor. It also inhibits activated oxygen species production and influences cell adhesion. Thus it can be concluded that Aceclofenac may be a better option for the management of pain.
BRAND NAME- Flexi,Riservix,Movex,Acecol etc.
Although cyclooxygenase-2 selective inhibitors (coxibs) represent a new class of analgesic and anti-inflammatory drugs that exhibits preference for inhibition of cyclooxygenase-2, its cardiovascular safety is controversial, since trial showed increased incidence of cardiovascular events in patients receiving coxibs. There is a need of a drug, which has high efficacy like traditional NSAIDs, shows high GI tolerability like selective cox-2 inhibitors but have no adverse cardiovascular effects.
Aceclofenac has been shown to have potent analgesic and anti-inflammatory activities, similar to indomethacin and diclofenac and due to its preferential cox-2 blockade it has better safety than conventional NSAIDs with respect to adverse effects on gastrointestinal and cardiovascular system.
INTRODUCTION
The pain is symptomatic of some form of dysfunction and resultant inflammatory processes in the body. A survey conducted for the WHO reported that one adult in five suffers from chronic non-malignant pain, which mostly occurs in the back, head, joints and limbs. More than 15% of the worldwide population suffers for instance from some form of osteoarthritis, and this incidence is even higher in the elderly. As the world population is grows older, this incidence will continue to rise.
The pain has been defined as a characteristic sensation arising from a noxious stimulus, which includes its neurophysiological aspect. Sherrington, in his classic definition has further included the reactive component of pain, i.e. the "psychical adjuvant of an imperative protective reflex". This indicates that pain also has a survival value for the species. There are two main classes of pain superficial and deep. Some pain receptors in the body are probably chemoreceptors, as a wide variety of compounds, including autacoids like bradykinin, and several of the prostaglandins, can elicit the pain. Drugs can alter the pain experience in three ways (Pain reception, perception, and reaction) the first that can be intercepted is peripheral pain reception at the nerve endings. This modality is susceptible to non-narcotic analgesic and local anesthesia. The second step, which can be modified, is pain perception at the level of the CNS. Both, narcotic and non-narcotic analgesics interfere with this level of pain integration. The third step, which can be influenced, is pain reaction.
Mechanism of pain & Inflammation:
Prostaglandins are implicated in the inflammatory response and are sensitizing nociceptors to the actions of other Mediators, occurring during acute and chronic inflammatory illness, prostaglandins are produced at the site of inflammation where it is believed that they mediate many of symptoms of inflammation such as oedema and pain.
Arachidonic acid is released from cell membranes by phospholipases, cyclooxygenases catalyze the addition of molecular oxygen to arachidonic acid to form in initially the endoperoxide intermediate prostaglandin G2. The same enzymes also process peroxidase activity, which catalyzes the reduction of these prostaglandins to form PGH2. PGH 2 may then react with a number of enzymes sometimes called isomerases to become one of the prostaglandins or thromboxanes.
Role of Non-Steroidal Anti inflammatory drugs in pain (NSAIDs)
Orally administered NSAIDS play an important role in symptomatic management of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis and other acute pain conditions. In general, they produce their anti-inflammatory and analgesic effects by inhibiting cyclooxygenase and this preventing the production of prostaglandins from arachidonic acid. It has been suggested that some NSAIDS inhibit leukotriene production via lipooxygenase inhibition.
ACECLOFENAC
Aceclofenac is an orally administered phenyl acetic acid derivatives with effects on a variety of inflammatory mediators.
Aceclofenac contains not less than 99.0% and not more than the equivalent of 101.0 percent of 2-[[2-[2-[(2, 6-dichlorophenyl) amino] phenyl] acetyl] oxy] acetic acid.
It is a white or almost white crystalline powder. It is an effective analgesic and anti-inflammatory agent with a good tolerability profile. Through its analgesic and anti-inflammatory properties, aceclofenac provides symptomatic relief in a variety of painful conditions. A reduction in the stimulated generation of reactive oxygen species (O2), which may play a role in joint damage, was observed after 15 days in these patients, but after 180 days. At day 180, O2 release was similar to that seen in a group of 41 healthy untreated individuals.
Structure Activity Relationship
Structure-activity relationship in this series, have not been extensively studied. It does appear that the function of the two o-chloro groups is to force the anilino-phenyl ring out of the plane of the phenylacetic acid portion, this twisting effect being important in the binding of NSAIDs to the active site of the cyclooxygenase enzyme.
Pharmacology
The mode of action of aceclofenac is largely based on the inhibition of prostaglandin synthesis. Aceclofenac is a potent inhibitor of the enzyme cyclooxygenase, which is involved in the production of prostaglandins.
The Drugs inhibits synthesis of the inflammatory cytokines interleukin (IL)-1 and tumor necrosis factor and prostaglandin E2 (PGE2) production. Effects on cell adhesion molecular from neurophils have also been noted. In vitro data indicate inhibition of cyclooxygenase (Cox)-1 and 2 by aceclofenac in whole blood assays, with selectivity for Cox-2 being evident.
Aceclofenac has shown stimulatory effects on cartilage matrix synthesis that may be linked to the ability of the drug to inhibit IL-1 activity. In vitro data indicate stimulation by the drug of synthesis of glycosaminoglycan in osteoarthritic cartilage. There is also evidence that aceclofenac stimulates the synthesis of IL-1 receptor antagonist in human articular chondrocytes subjected to inflammatory stimuli and that 4'-hydroxyacelofenac has chondroprotective properties attributable to suppression of IL-1 mediated promatrix metalloproteinase production and proteoglycan release.
In patients with osteoarthritis of the knee, aceclofenac decrease pain reduces disease severity and improves the functional capacity of the knee. It reduces joint inflammation, pain intensity and the duration of morning stiffness in patients with rheumatoid arthritis. The duration of morning stiffness and pain intensity are reduced and spinal mobility improved, by aceclofenac in patients with ankylosing spondylitis.
PHARMACOKINETICS
Aceclofenac is rapidly and completely absorbed after oral administration, peak plasma concentrations are reached 1 to 3 hours after an oral dose. The drug is highly protein bound (7.99%). The presence of food does alter the extent of absorption of aceclofenac but the absorption rate is reduced. The plasma concentration of aceclofenac was approximately twice that in synovial fluid after multiple doses of the drug in-patient with knee pain and synovial fluid effusion. Aceclofenac is metabolized to a major metabolite, 4'-hydroxyaceclofenac and to a number of other metabolites including 5-hydroxyaceclofenac, 4'-hydroxydiclofenac, diclofenac and 5-hydroxydiclofenac. Renal excretion is the main route of elimination of aceclofenac with 70 to 80% of an administered dose found in the urine, mainly as the glucuronides of aceclofenac and its metabolites of each dose of aceclofenac, 20% is excreted in the faeces. The plasma elimination half-life of the drug is approximately 4 hours.
Drug Interactions
Aceclofenac may increase plasma concentrations of lithium, digoxin and methotrexate, increase the activity of anticoagulant, inhibits the activity of diuretics, enhance cyclosporin nephrotoxicity and precipitate convulsions when co-administered with quinolone antibiotics. Furthermore, hypo or hyperglycaemia may result from the concomitant administration of aceclofenac and antidiabetic drugs, although this is rare. The co administration of aceclofenac with other NSAIDS of corticosteroids may results in increased frequency of adverse event.
Adverse Drug Reaction
Aceclofenac is well tolerated, with most adverse events being minor and reversible and affecting mainly the GI system. Most common events include dyspepsia (7.5%), abdominal pain (6.2%), nausea (1.5%), diarrhea (1.5%), flatulence (0.8%), gastritis (0.6%), constipation (0.5%), vomiting (0.5%), ulcerative stomatitis (0.1%), pancreatitis (0.1%).
Although the incidence of gastro intestinal adverse events with aceclofenac was similar to those of comparator NSAIDS in individual clinical trials, withdrawal rates due to these events were significantly lower aceclofenac than with ketoprofen and tenoxicam.
Other adverse effect, which is not common such as dizziness (1%), vertigo (0.3%), and rare cases: par aesthesia and tremor.
Dosage and Administration
The usual dose of aceclofenac is 100 mg given twice daily by mouth, one tablet in the morning and one in the evening. There is no evidence that the dosage of aceclofenac needs to be modified in patients with mild renal impairment, but as with other NSAIDS caution should be exercised.
Aceclofenac Balanced Cox Inhibitor
It has been suggested that aceclofenac blocks PGE2 production via cyclo-oxygenase (cox)-1 and cox-2 inhibition after intracellular metabolism to 4'-hydroxyaceclofenac and diclofenac in human rheumatoid synovial and other inflammatory cells.
However data from human whole blood assays show inhibition of cox-2 (with minimal effects on cox-1) by both the parent compound and 4'-hydroxyaceclofenac. IC50 values of cox-1 and cox-2 respectively were > 100 and 0.8 for aceclofenac and > 100 and 36 for 4'-hydroxyaceclofenac.
IC 50
Cox-1 Cox-2
Aceclofenac > 100 0.8
4'-hydroxyaceclofenac > 100 36
Further evidence of cox-2 selectivity of aceclofenac has been shown by an IC50 ratio (cox-2: cox-1) of 0.26, which fell between IC50 ratios of 0.7 and 0.12 for the cox-2 inhibitors celecoxib and rofecoxib, respectively in other study. Most recent data have shown aceclofenac to have the highest cox-1: cox-2 IC 50 ratio of a range of agents, including rofecoxib, celecoxib, nimesulide, diclofenac and tenoxicam.
Drugs IC50
Aceclofenac 0.26
Celecoxib 0.7
Rofecoxib 0.12
Aceclofenac may prevent the degradation of articular connective tissue in patients with rheumatoid arthritis and osteoarthritis and this should be classified as unique NSAIDs.
Aceclofenac - Clinical Efficacy
In large trials of 2 to 6 months duration, aceclofenac significantly reduced pain and improves functional capacity and mobility relative to baseline in patients with osteoarthritis, rheumatoid arthritis or ankylosing spondylitis and reduces inflammation in patients with rheumatoid arthritis. No head to head comparison between aceclofenac and coxibs have been performed, nor for efficacy neither for tolerance.
Aceclofenac in osteoarthritis
In patients with osteoarthritis of the knee, aceclofenac decreases pain, reduces disease severity and improves the functional capacity of the knee to a similar extent to diclofenac, piroxicam, and naproxen.
Aceclofenac in rheumatoid arthritis
The anti-inflammatory and analgesic efficacy of aceclofenac is similar to that of ketoprofen, indomethacin, tenoxicam and diclofenac in patients with rheumatoid arthritis. In randomized, double blind trials in 169 to 261 patients, aceclofenac (100 mg twice daily for 3 or 6 months) significantly reduced relative to baseline joint inflammation, pain intensity and the duration of morning stiffness and improved handgrip strength.
Aceclofenac in ankylosing spondylitis
The duration of morning stiffness and pain intensity are reduced and spinal mobility improved, by aceclofenac in patients with ankylosing spondylitis, with improvements being similar to those observed with indomethacin, naproxen or tenoxicam. These effects were observed after aceclofenac 100 mg twice daily for 3 months in randomized, double blind trials involving 104 to 308 patients.
Aceclofenac in dental pain
The analgesic efficacy as single doses of aceclofenac has been assessed in patients with moderate to severe tooth pain and in extraction of impacted third molars. The analgesic efficacy of single doses of aceclofenac 50, 100 and 150 mg was greater than that of placebo in patients with moderate to severe tooth pain or pain caused by extraction of impacted third molars.
Aceclofenac in postoperative pain
The analgesic efficacy of aceclofenac has been shown in comparisons with paracetamol in women undergoing episiotomy. Aceclofenac 100 mg was superior to paracetamol 650 mg in providing relief from postepisiotomy pain, particularly 3 to 5 hours after ingestion.
Aceclofenac in Dysmenorrhoea
In a more recent noncomparative study in 1338 women with dysmenorrohea treated for first 3 days of 2 consecutive cycles.
Aceclofenac in acute lumbago
Aceclofenac (150 mg intramuscularly for 2 days, then 100 mg orally, both twice daily) was superior to diclofenac in alleviating functional impairment in a 7 days study in 100 patients with acute lumbago. Aceclofenac 100 mg twice daily was associated with symptomatic relief of acute low back pain in a non-comparative study in 67 pateints.
Aceclofenac in musculoskeletal trauma
Aceclofenac 100 mg twice daily has also been assessed in patients with musculoskeletal trauma, although only non-comparative studies are available.
Aceclofenac Gonalgia (Knee pain)
A controlled double blind study was performed with aceclofenac comparing it with diclofenac in 40 patients with acute or chronic gonalgia. The results of the trial indicate slightly superior activity, although there was no statistically significant difference between two drugs.
CONCLUSION
Aceclofenac is superior form other NSAIDs as it has selectivity for cox-2, a beneficial cox inhibitor, well tolerated, better GI tolerability and improved cardiovascular safety when compared to other selective cox-2 inhibitors. It also shows Increased matrix component synthesis and protection of chondrocytes against apoptosis. Aceclofenac has a faster and more potent effect than the other NSAIDs. It efficiently interferes with Neutrophils adhesion to endothelium and this effect may represent an additional relevant mechanism in its anti-inflammatory activity. Aceclofenac has an outstanding anti-inflammatory profile, involving a classical inhibition of prostaglandins E2, a decrease in the expression of several cytokines including interleukin and tumor necrosis factor. It also inhibits activated oxygen species production and influences cell adhesion. Thus it can be concluded that Aceclofenac may be a better option for the management of pain.
BRAND NAME- Flexi,Riservix,Movex,Acecol etc.
Antacid
Antacid (Oral Route)
Bangladeshi Brand Names
• Milk of Magnesia
• Antacid plus
• Antacid Max
• Oxicone • Oxicone M
• Megaplus
• Lactmeal
• Flatamal DS
US Brand Names
• Alternagel
• Alu-Cap
• Brioschi
• Dewee's Carminative
• Dulcolax Milk of Magnesia
• Kaopectate
• Mag-Gel 600 • Mag-Ox 400
• Pepto Bismol
• Phillips Milk of Magnesia
• Riopan
• Rolaids
• Tums
Canadian Brand Names
• Alumag
• Amphojel
• Amphojel 500
• Antacid
• Antacid Plus
• Antacid Stomaax • Antacid Stomaax Plus Simethicone Antiflatulent
• Baros
• Bismuth Extra Strength
• Bismuth Original Formula
• Diovol
• Diovol Ex
Description
Antacids are taken by mouth to relieve heartburn, sour stomach, or acid indigestion. They work by neutralizing excess stomach acid. Some antacid combinations also contain simethicone, which may relieve the symptoms of excess gas. Antacids alone or in combination with simethicone may also be used to treat the symptoms of stomach or duodenal ulcers.
With larger doses than those used for the antacid effect, magnesium hydroxide (magnesia) and magnesium oxide antacids produce a laxative effect. The information that follows applies only to their use as an antacid.
Some antacids, like aluminum carbonate and aluminum hydroxide, may be prescribed with a low-phosphate diet to treat hyperphosphatemia (too much phosphate in the blood). Aluminum carbonate and aluminum hydroxide may also be used with a low-phosphate diet to prevent the formation of some kinds of kidney stones. Aluminum hydroxide may also be used for other conditions as determined by your doctor.
These medicines are available without a prescription. However, your doctor may have special instructions on the proper use and dose of these medicines for your medical problem.
Make certain your health care professional knows if you are on a low-sodium diet. Some antacids contain large amounts of sodium.
This product is available in the following dosage forms:
• Liquid
• Tablet
• Powder for Suspension
• Suspension
• Tablet, Chewable
• Capsule
• Solution
• Tablet, Extended Release
• Wafer
• Tablet, Effervescent
• Granule
• Powder, Effervescent
Before Using
Allergies
Tell your doctor if you have ever had any unusual or allergic reaction to medicines in this group or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Pediatric
Antacids should not be given to young children (under 6 years of age) unless ordered by their doctor. Since children cannot usually describe their symptoms very well, a doctor should first check the child. The child may have a condition that needs other treatment. If so, antacids will not help and may even cause unwanted effects or make the condition worse. In addition, aluminum- or magnesium-containing medicines should not be given to premature or very young children because they may cause serious side effects, especially when given to children who have kidney disease or who are dehydrated.
Geriatric
Aluminum-containing antacids should not be used by elderly persons with bone problems or with Alzheimer's disease. The aluminum may cause their condition to get worse.
Pregnancy
Studies on effects in pregnancy have not been done in either humans or animals. However, there have been reports of antacids causing side effects in babies whose mothers took antacids for a long time, especially in high doses during pregnancy. Also, sodium-containing medicines should be avoided if you tend to retain (keep) body water.
Breastfeeding
Some aluminum-, calcium-, or magnesium-containing antacids may pass into breast milk. However, these medicines have not been reported to cause problems in nursing babies.
Drug Interactions
Using medicines in this class with any of the following medicines is not recommended. Your doctor may decide not to treat you with a medication in this class or change some of the other medicines you take.
• Amantadine
• Atropine
• Belladonna
• Belladonna Alkaloids
• Benztropine
• Biperiden
• Clidinium
• Dicyclomine
• Eplerenone
• Glycopyrrolate
• Hyoscyamine
• Methscopolamine
• Oxybutynin
• Procyclidine
• Scopolamine
• Solifenacin
• Tolterodine
• Trihexyphenidyl
Using medicines in this class with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
• Alacepril
• Amiloride
• Atazanavir
• Benazepril
• Canrenoate
• Captopril
• Cilazapril
• Dasatinib
• Delapril
• Delavirdine
• Enalaprilat
• Enalapril Maleate
• Fosinopril
• Imidapril
• Indomethacin
• Licorice
• Lisinopril
• Methotrexate
• Moexipril
• Mycophenolate Mofetil
• Mycophenolic Acid
• Pentopril
• Perindopril
• Quinapril
• Quinine
• Ramipril
• Spirapril
• Spironolactone
• Temocapril
• Tizanidine
• Tolazoline
• Trandolapril
• Triamterene
• Zofenopril
Other Interactions
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.
Other Medical Problems
The presence of other medical problems may affect the use of medicines in this class. Make sure you tell your doctor if you have any other medical problems, especially:
• Alzheimer's disease (for aluminum-containing antacids only) or
• Appendicitis (or signs of) or
• Bone fractures or
• Colitis or
• Constipation (severe and continuing) or
• Hemorrhoids or
• Intestinal blockage or
• Intestinal or rectal bleeding—Antacids may make these conditions worse
•
• Colostomy or
• Ileostomy or
• Inflamed bowel—Use of antacids may cause the body to retain (keep) water and electrolytes such as sodium and/or potassium
• Edema (swelling of feet or lower legs) or
• Heart disease or
• Liver disease or
• Toxemia of pregnancy—Use of sodium-containing antacids may cause the body to retain (keep) water
• Kidney disease—Antacids may cause higher blood levels of aluminum, calcium, or magnesium, which may increase the risk of serious side effects
• Sarcoidosis—Use of calcium-containing antacids may cause kidney problems or too much calcium in the blood
• Underactive parathyroid glands—Use with calcium-containing antacids may cause too much calcium in the blood
Proper Use
For patients taking the chewable tablet form of this medicine:
• Chew the tablets well before swallowing. This is to allow the medicine to work faster and be more effective.
For patients taking this medicine for a stomach or duodenal ulcer:
• Take it exactly as directed and for the full time of treatment as ordered by your doctor, to obtain maximum relief of your symptoms.
• Take it 1 and 3 hours after meals and at bedtime for best results, unless otherwise directed by your doctor.
For patients taking aluminum carbonate or aluminum hydroxide to prevent kidney stones:
• Drink plenty of fluids for best results, unless otherwise directed by your doctor.
For patients taking aluminum carbonate or aluminum hydroxide for hyperphosphatemia (too much phosphate in the blood):
• Your doctor may want you to follow a low-phosphate diet. If you have any questions about this, check with your doctor.
Dosing
The dose medicines in this class will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of these medicines. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
Missed Dose
If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
Storage
Keep out of the reach of children.
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Do not keep outdated medicine or medicine no longer needed.
Precautions
If this medicine has been ordered by your doctor and you will be taking it in large doses, or for a long time, your doctor should check your progress at regular visits. This is to make sure the medicine does not cause unwanted effects.
Some tests may be affected by this medicine. Tell the doctor in charge that you are taking this medicine before you have any tests to determine how much acid your stomach produces.
Do not take this medicine:
• if you have any signs of appendicitis or inflamed bowel (such as stomach or lower abdominal pain, cramping, bloating, soreness, nausea, or vomiting). Instead, check with your doctor as soon as possible.
• within 1 to 2 hours or more of taking other medicine by mouth. To do so may keep the other medicine from working properly.
For patients on a sodium-restricted diet:
• Some antacids (especially those containing sodium bicarbonate) contain a large amount of sodium. If you have any questions about this, check with your health care professional.
For patients taking this medicine for increased stomach acid:
• Do not take it for more than 2 weeks unless otherwise directed by your doctor. Antacids should be used only for occasional relief.
• If your stomach problem is not helped by the antacid or if it keeps coming back, check with your doctor.
• Using magnesium- or sodium bicarbonate-containing antacids too often, or in high doses, may produce a laxative effect. This happens fairly often and depends on the individual's sensitivity to the medicine.
For patients taking aluminum-containing antacids (including magaldrate):
• Before you have any test in which a radiopharmaceutical will be used, tell the doctor in charge that you are taking this medicine. The results of the test may be affected by aluminum-containing antacids.
For patients taking calcium- or sodium bicarbonate-containing antacids
• Do not take the antacid with large amounts of milk or milk products. To do so may increase the chance of side effects.
Side Effects
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Along with its needed effects, a medicine may cause some unwanted effects. Although the following side effects occur very rarely when this medicine is taken as recommended, they may be more likely to occur if: too much medicine is taken; it is taken in large doses; it is taken for a long time; or it is taken by patients with kidney disease.
Check with your doctor as soon as possible if any of the following side effects occur:
For aluminum-containing antacids (including magaldrate)
• Bone pain
• Constipation (severe and continuing)
• Feeling of discomfort (continuing)
• Loss of appetite (continuing)
• Mood or mental changes
• Muscle weakness
• Swelling of wrists or ankles
• Weight loss (unusual)
For calcium-containing antacids
• Constipation (severe and continuing)
• Difficult or painful urination
• Frequent urge to urinate
• Headache (continuing)
• Loss of appetite (continuing)
• Mood or mental changes
• Muscle pain or twitching
• Nausea or vomiting
• Nervousness or restlessness
• Slow breathing
• Unpleasant taste
• Unusual tiredness or weakness
For magnesium-containing antacids (including magaldrate)
• Difficult or painful urination (with magnesium trisilicate)
• Dizziness or lightheadedness
• Feeling of discomfort (continuing)
• Irregular heartbeat
• Loss of appetite (continuing)
• Mood or mental changes
• Muscle weakness
• Unusual tiredness or weakness
• Weight loss (unusual)
For sodium bicarbonate-containing antacids
• Frequent urge to urinate
• Headache (continuing)
• Loss of appetite (continuing)
• Muscle pain or twitching
• Nausea or vomiting
• Nervousness or restlessness
• Slow breathing
• Swelling of feet or lower legs
• Unpleasant taste
• Unusual tiredness or weakness
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
More common
• Chalky taste Less common
• Constipation (mild)
• Diarrhea or laxative effect
• Increased thirst
• Speckling or whitish discoloration of stools
• Stomach cramps
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects.
Bangladeshi Brand Names
• Milk of Magnesia
• Antacid plus
• Antacid Max
• Oxicone • Oxicone M
• Megaplus
• Lactmeal
• Flatamal DS
US Brand Names
• Alternagel
• Alu-Cap
• Brioschi
• Dewee's Carminative
• Dulcolax Milk of Magnesia
• Kaopectate
• Mag-Gel 600 • Mag-Ox 400
• Pepto Bismol
• Phillips Milk of Magnesia
• Riopan
• Rolaids
• Tums
Canadian Brand Names
• Alumag
• Amphojel
• Amphojel 500
• Antacid
• Antacid Plus
• Antacid Stomaax • Antacid Stomaax Plus Simethicone Antiflatulent
• Baros
• Bismuth Extra Strength
• Bismuth Original Formula
• Diovol
• Diovol Ex
Description
Antacids are taken by mouth to relieve heartburn, sour stomach, or acid indigestion. They work by neutralizing excess stomach acid. Some antacid combinations also contain simethicone, which may relieve the symptoms of excess gas. Antacids alone or in combination with simethicone may also be used to treat the symptoms of stomach or duodenal ulcers.
With larger doses than those used for the antacid effect, magnesium hydroxide (magnesia) and magnesium oxide antacids produce a laxative effect. The information that follows applies only to their use as an antacid.
Some antacids, like aluminum carbonate and aluminum hydroxide, may be prescribed with a low-phosphate diet to treat hyperphosphatemia (too much phosphate in the blood). Aluminum carbonate and aluminum hydroxide may also be used with a low-phosphate diet to prevent the formation of some kinds of kidney stones. Aluminum hydroxide may also be used for other conditions as determined by your doctor.
These medicines are available without a prescription. However, your doctor may have special instructions on the proper use and dose of these medicines for your medical problem.
Make certain your health care professional knows if you are on a low-sodium diet. Some antacids contain large amounts of sodium.
This product is available in the following dosage forms:
• Liquid
• Tablet
• Powder for Suspension
• Suspension
• Tablet, Chewable
• Capsule
• Solution
• Tablet, Extended Release
• Wafer
• Tablet, Effervescent
• Granule
• Powder, Effervescent
Before Using
Allergies
Tell your doctor if you have ever had any unusual or allergic reaction to medicines in this group or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Pediatric
Antacids should not be given to young children (under 6 years of age) unless ordered by their doctor. Since children cannot usually describe their symptoms very well, a doctor should first check the child. The child may have a condition that needs other treatment. If so, antacids will not help and may even cause unwanted effects or make the condition worse. In addition, aluminum- or magnesium-containing medicines should not be given to premature or very young children because they may cause serious side effects, especially when given to children who have kidney disease or who are dehydrated.
Geriatric
Aluminum-containing antacids should not be used by elderly persons with bone problems or with Alzheimer's disease. The aluminum may cause their condition to get worse.
Pregnancy
Studies on effects in pregnancy have not been done in either humans or animals. However, there have been reports of antacids causing side effects in babies whose mothers took antacids for a long time, especially in high doses during pregnancy. Also, sodium-containing medicines should be avoided if you tend to retain (keep) body water.
Breastfeeding
Some aluminum-, calcium-, or magnesium-containing antacids may pass into breast milk. However, these medicines have not been reported to cause problems in nursing babies.
Drug Interactions
Using medicines in this class with any of the following medicines is not recommended. Your doctor may decide not to treat you with a medication in this class or change some of the other medicines you take.
• Amantadine
• Atropine
• Belladonna
• Belladonna Alkaloids
• Benztropine
• Biperiden
• Clidinium
• Dicyclomine
• Eplerenone
• Glycopyrrolate
• Hyoscyamine
• Methscopolamine
• Oxybutynin
• Procyclidine
• Scopolamine
• Solifenacin
• Tolterodine
• Trihexyphenidyl
Using medicines in this class with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
• Alacepril
• Amiloride
• Atazanavir
• Benazepril
• Canrenoate
• Captopril
• Cilazapril
• Dasatinib
• Delapril
• Delavirdine
• Enalaprilat
• Enalapril Maleate
• Fosinopril
• Imidapril
• Indomethacin
• Licorice
• Lisinopril
• Methotrexate
• Moexipril
• Mycophenolate Mofetil
• Mycophenolic Acid
• Pentopril
• Perindopril
• Quinapril
• Quinine
• Ramipril
• Spirapril
• Spironolactone
• Temocapril
• Tizanidine
• Tolazoline
• Trandolapril
• Triamterene
• Zofenopril
Other Interactions
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.
Other Medical Problems
The presence of other medical problems may affect the use of medicines in this class. Make sure you tell your doctor if you have any other medical problems, especially:
• Alzheimer's disease (for aluminum-containing antacids only) or
• Appendicitis (or signs of) or
• Bone fractures or
• Colitis or
• Constipation (severe and continuing) or
• Hemorrhoids or
• Intestinal blockage or
• Intestinal or rectal bleeding—Antacids may make these conditions worse
•
• Colostomy or
• Ileostomy or
• Inflamed bowel—Use of antacids may cause the body to retain (keep) water and electrolytes such as sodium and/or potassium
• Edema (swelling of feet or lower legs) or
• Heart disease or
• Liver disease or
• Toxemia of pregnancy—Use of sodium-containing antacids may cause the body to retain (keep) water
• Kidney disease—Antacids may cause higher blood levels of aluminum, calcium, or magnesium, which may increase the risk of serious side effects
• Sarcoidosis—Use of calcium-containing antacids may cause kidney problems or too much calcium in the blood
• Underactive parathyroid glands—Use with calcium-containing antacids may cause too much calcium in the blood
Proper Use
For patients taking the chewable tablet form of this medicine:
• Chew the tablets well before swallowing. This is to allow the medicine to work faster and be more effective.
For patients taking this medicine for a stomach or duodenal ulcer:
• Take it exactly as directed and for the full time of treatment as ordered by your doctor, to obtain maximum relief of your symptoms.
• Take it 1 and 3 hours after meals and at bedtime for best results, unless otherwise directed by your doctor.
For patients taking aluminum carbonate or aluminum hydroxide to prevent kidney stones:
• Drink plenty of fluids for best results, unless otherwise directed by your doctor.
For patients taking aluminum carbonate or aluminum hydroxide for hyperphosphatemia (too much phosphate in the blood):
• Your doctor may want you to follow a low-phosphate diet. If you have any questions about this, check with your doctor.
Dosing
The dose medicines in this class will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of these medicines. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
Missed Dose
If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
Storage
Keep out of the reach of children.
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Do not keep outdated medicine or medicine no longer needed.
Precautions
If this medicine has been ordered by your doctor and you will be taking it in large doses, or for a long time, your doctor should check your progress at regular visits. This is to make sure the medicine does not cause unwanted effects.
Some tests may be affected by this medicine. Tell the doctor in charge that you are taking this medicine before you have any tests to determine how much acid your stomach produces.
Do not take this medicine:
• if you have any signs of appendicitis or inflamed bowel (such as stomach or lower abdominal pain, cramping, bloating, soreness, nausea, or vomiting). Instead, check with your doctor as soon as possible.
• within 1 to 2 hours or more of taking other medicine by mouth. To do so may keep the other medicine from working properly.
For patients on a sodium-restricted diet:
• Some antacids (especially those containing sodium bicarbonate) contain a large amount of sodium. If you have any questions about this, check with your health care professional.
For patients taking this medicine for increased stomach acid:
• Do not take it for more than 2 weeks unless otherwise directed by your doctor. Antacids should be used only for occasional relief.
• If your stomach problem is not helped by the antacid or if it keeps coming back, check with your doctor.
• Using magnesium- or sodium bicarbonate-containing antacids too often, or in high doses, may produce a laxative effect. This happens fairly often and depends on the individual's sensitivity to the medicine.
For patients taking aluminum-containing antacids (including magaldrate):
• Before you have any test in which a radiopharmaceutical will be used, tell the doctor in charge that you are taking this medicine. The results of the test may be affected by aluminum-containing antacids.
For patients taking calcium- or sodium bicarbonate-containing antacids
• Do not take the antacid with large amounts of milk or milk products. To do so may increase the chance of side effects.
Side Effects
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Along with its needed effects, a medicine may cause some unwanted effects. Although the following side effects occur very rarely when this medicine is taken as recommended, they may be more likely to occur if: too much medicine is taken; it is taken in large doses; it is taken for a long time; or it is taken by patients with kidney disease.
Check with your doctor as soon as possible if any of the following side effects occur:
For aluminum-containing antacids (including magaldrate)
• Bone pain
• Constipation (severe and continuing)
• Feeling of discomfort (continuing)
• Loss of appetite (continuing)
• Mood or mental changes
• Muscle weakness
• Swelling of wrists or ankles
• Weight loss (unusual)
For calcium-containing antacids
• Constipation (severe and continuing)
• Difficult or painful urination
• Frequent urge to urinate
• Headache (continuing)
• Loss of appetite (continuing)
• Mood or mental changes
• Muscle pain or twitching
• Nausea or vomiting
• Nervousness or restlessness
• Slow breathing
• Unpleasant taste
• Unusual tiredness or weakness
For magnesium-containing antacids (including magaldrate)
• Difficult or painful urination (with magnesium trisilicate)
• Dizziness or lightheadedness
• Feeling of discomfort (continuing)
• Irregular heartbeat
• Loss of appetite (continuing)
• Mood or mental changes
• Muscle weakness
• Unusual tiredness or weakness
• Weight loss (unusual)
For sodium bicarbonate-containing antacids
• Frequent urge to urinate
• Headache (continuing)
• Loss of appetite (continuing)
• Muscle pain or twitching
• Nausea or vomiting
• Nervousness or restlessness
• Slow breathing
• Swelling of feet or lower legs
• Unpleasant taste
• Unusual tiredness or weakness
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
More common
• Chalky taste Less common
• Constipation (mild)
• Diarrhea or laxative effect
• Increased thirst
• Speckling or whitish discoloration of stools
• Stomach cramps
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects.
Tuesday, August 17, 2010
RANITIDINE
Generic Name: ranitidine (ra NI ti deen)
Brand Names: Ranitid, Neotack, Xantid
Suffering Acid Reflux
naturalhealthandbeautyinfo.com/acidIts Painful, It Burns, But Suffer No More. Try These Proven Remedies
What is ranitidine?
Ranitidine is in a group of drugs called histamine-2 blockers. Ranitidine works by reducing the amount of acid your stomach produces.
Ranitidine is used to treat and prevent ulcers in the stomach and intestines. It also treats conditions in which the stomach produces too much acid, such as Zollinger-Ellison syndrome. Ranitidine also treats gastroesophageal reflux disease (GERD) and other conditions in which acid backs up from the stomach into the esophagus, causing heartburn.
Important information about ranitidine
Before using this medication, tell your doctor if you are allergic to any drugs, or if you have kidney disease, liver disease, or porphyria.
Using ranitidine may increase your risk of developing pneumonia. Symptoms of pneumonia include chest pain, fever, feeling short of breath, and coughing up green or yellow mucus. Talk with your doctor about your specific risk of developing pneumonia.
Ranitidine granules and effervescent tablets must be dissolved in water before you take them.
Your doctor may recommend an antacid to help relieve pain. Carefully follow your doctor's directions about the type of antacid to use, and when to use it.
Avoid drinking alcohol. It can increase the risk of damage to your stomach. It may take up to 8 weeks of using ranitidine before your ulcer heals. For best results, keep using the medication as directed. Talk with your doctor if your symptoms do not improve after 6 weeks of treatment.
Heartburn can be confused with early symptoms of heart attack. Seek emergency medical attention if you have chest pain or heavy feeling, dizziness, pain spreading to the arm or shoulder, sweating, nausea or vomiting, and a general ill feeling.
Before using ranitidine
Do not use this medication if you are allergic to ranitidine.
Ask a doctor or pharmacist if it is safe for you to take ranitidine if you have:
* kidney disease;
* liver disease; or
* porphyria.
The ranitidine effervescent tablet may contain phenylalanine. Talk to your doctor before using this form of ranitidine if you have phenylketonuria (PKU).
FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Ranitidine passes into breast milk. Do not take ranitidine without telling your doctor if you are breast-feeding a baby.
See also: Pregnancy and breastfeeding warnings in more details
Using ranitidine may increase your risk of developing pneumonia. Symptoms of pneumonia include chest pain, fever, feeling short of breath, and coughing up green or yellow mucus. Talk with your doctor about your specific risk of developing pneumonia.
How should I take ranitidine?
Take ranitidine exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.
Your doctor may recommend an antacid to help relieve pain. Carefully follow your doctor's directions about the type of antacid to use, and when to use it.
Do not crush, chew, or break the ranitidine effervescent tablet, and do not allow it to dissolve on your tongue. The 25-milligram effervescent tablet must be dissolved in at least 1 teaspoon of water before swallowing. The150-milligram effervescent tablet should be dissolved in 6 to 8 ounces of water.
Allow the tablet to dissolve completely in the water, and then drink the entire mixture. If you are giving this medicine to a child, you may draw the liquid mixture into a medicine dropper and empty the dropper into the child's mouth.
Ranitidine granules should be mixed with 6 to 8 ounces of water before drinking.
Measure the liquid form of ranitidine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.
It may take up to 8 weeks of using this medicine before your ulcer heals. For best results, keep using the medication as directed. Talk with your doctor if your symptoms do not improve after 6 weeks of treatment.
This medication can cause you to have unusual results with certain medical tests. Tell any doctor who treats you that you are using ranitidine.
Store ranitidine at room temperature away from moisture, heat, and light.
See also: Ranitidine dosage in more detail
What happens if I miss a dose?
Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.
What happens if I overdose?
Seek emergency medical attention if you think you have used too much of this medicine.
Overdose symptoms may include lack of coordination, feeling light-headed, or fainting.
What should I avoid while taking ranitidine?
Avoid drinking alcohol. It can increase the risk of damage to your stomach.
Ranitidine side effects
Stop using ranitidine and get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have any of these serious side effects:
* chest pain, fever, feeling short of breath, coughing up green or yellow mucus;
* easy bruising or bleeding, unusual weakness;
* fast or slow heart rate;
* problems with your vision;
* fever, sore throat, and headache with a severe blistering, peeling, and red skin rash; or
* nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice
(yellowing of the skin or eyes).
Less serious ranitidine side effects may include:
* headache (may be severe);
* drowsiness, dizziness;
* sleep problems (insomnia);
* decreased sex drive, impotence, or difficulty having an orgasm; or
* swollen or tender breasts (in men);
* nausea, vomiting, stomach pain; or
* diarrhea or constipation.
This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.
What other drugs will affect ranitidine?
Before taking ranitidine, tell your doctor if you are taking triazolam (Halcion). You may not be able to use ranitidine, or you may need dosage adjustments or special tests during treatment.
There may be other drugs that can interact with ranitidine, or be affected by ranitidine. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.
Where can I get more information?
* Your pharmacist can provide more information about ranitidine.
* Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.
* Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.
Brand Names: Ranitid, Neotack, Xantid
Suffering Acid Reflux
naturalhealthandbeautyinfo.com/acidIts Painful, It Burns, But Suffer No More. Try These Proven Remedies
What is ranitidine?
Ranitidine is in a group of drugs called histamine-2 blockers. Ranitidine works by reducing the amount of acid your stomach produces.
Ranitidine is used to treat and prevent ulcers in the stomach and intestines. It also treats conditions in which the stomach produces too much acid, such as Zollinger-Ellison syndrome. Ranitidine also treats gastroesophageal reflux disease (GERD) and other conditions in which acid backs up from the stomach into the esophagus, causing heartburn.
Important information about ranitidine
Before using this medication, tell your doctor if you are allergic to any drugs, or if you have kidney disease, liver disease, or porphyria.
Using ranitidine may increase your risk of developing pneumonia. Symptoms of pneumonia include chest pain, fever, feeling short of breath, and coughing up green or yellow mucus. Talk with your doctor about your specific risk of developing pneumonia.
Ranitidine granules and effervescent tablets must be dissolved in water before you take them.
Your doctor may recommend an antacid to help relieve pain. Carefully follow your doctor's directions about the type of antacid to use, and when to use it.
Avoid drinking alcohol. It can increase the risk of damage to your stomach. It may take up to 8 weeks of using ranitidine before your ulcer heals. For best results, keep using the medication as directed. Talk with your doctor if your symptoms do not improve after 6 weeks of treatment.
Heartburn can be confused with early symptoms of heart attack. Seek emergency medical attention if you have chest pain or heavy feeling, dizziness, pain spreading to the arm or shoulder, sweating, nausea or vomiting, and a general ill feeling.
Before using ranitidine
Do not use this medication if you are allergic to ranitidine.
Ask a doctor or pharmacist if it is safe for you to take ranitidine if you have:
* kidney disease;
* liver disease; or
* porphyria.
The ranitidine effervescent tablet may contain phenylalanine. Talk to your doctor before using this form of ranitidine if you have phenylketonuria (PKU).
FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Ranitidine passes into breast milk. Do not take ranitidine without telling your doctor if you are breast-feeding a baby.
See also: Pregnancy and breastfeeding warnings in more details
Using ranitidine may increase your risk of developing pneumonia. Symptoms of pneumonia include chest pain, fever, feeling short of breath, and coughing up green or yellow mucus. Talk with your doctor about your specific risk of developing pneumonia.
How should I take ranitidine?
Take ranitidine exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.
Your doctor may recommend an antacid to help relieve pain. Carefully follow your doctor's directions about the type of antacid to use, and when to use it.
Do not crush, chew, or break the ranitidine effervescent tablet, and do not allow it to dissolve on your tongue. The 25-milligram effervescent tablet must be dissolved in at least 1 teaspoon of water before swallowing. The150-milligram effervescent tablet should be dissolved in 6 to 8 ounces of water.
Allow the tablet to dissolve completely in the water, and then drink the entire mixture. If you are giving this medicine to a child, you may draw the liquid mixture into a medicine dropper and empty the dropper into the child's mouth.
Ranitidine granules should be mixed with 6 to 8 ounces of water before drinking.
Measure the liquid form of ranitidine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.
It may take up to 8 weeks of using this medicine before your ulcer heals. For best results, keep using the medication as directed. Talk with your doctor if your symptoms do not improve after 6 weeks of treatment.
This medication can cause you to have unusual results with certain medical tests. Tell any doctor who treats you that you are using ranitidine.
Store ranitidine at room temperature away from moisture, heat, and light.
See also: Ranitidine dosage in more detail
What happens if I miss a dose?
Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.
What happens if I overdose?
Seek emergency medical attention if you think you have used too much of this medicine.
Overdose symptoms may include lack of coordination, feeling light-headed, or fainting.
What should I avoid while taking ranitidine?
Avoid drinking alcohol. It can increase the risk of damage to your stomach.
Ranitidine side effects
Stop using ranitidine and get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have any of these serious side effects:
* chest pain, fever, feeling short of breath, coughing up green or yellow mucus;
* easy bruising or bleeding, unusual weakness;
* fast or slow heart rate;
* problems with your vision;
* fever, sore throat, and headache with a severe blistering, peeling, and red skin rash; or
* nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice
(yellowing of the skin or eyes).
Less serious ranitidine side effects may include:
* headache (may be severe);
* drowsiness, dizziness;
* sleep problems (insomnia);
* decreased sex drive, impotence, or difficulty having an orgasm; or
* swollen or tender breasts (in men);
* nausea, vomiting, stomach pain; or
* diarrhea or constipation.
This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.
What other drugs will affect ranitidine?
Before taking ranitidine, tell your doctor if you are taking triazolam (Halcion). You may not be able to use ranitidine, or you may need dosage adjustments or special tests during treatment.
There may be other drugs that can interact with ranitidine, or be affected by ranitidine. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.
Where can I get more information?
* Your pharmacist can provide more information about ranitidine.
* Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.
* Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.
Friday, August 6, 2010
Paracetamol
Paracetamol is a common medicine to everybody. It is most useful and well known to everybody. All of doctors prescribe this medicine often. There is no man who does not use paracetamol. Somebody uses this medicine without suggestion of doctor. But it is very risky to use any kind of medicine without prescription of a doctor.
PARACETAMOL
Paracetamol is a common medicine to everybody. It is most useful and well known to everybody. All of doctors prescribe this medicine often. There is no man who does not use paracetamol. Somebody uses this medicine without suggestion of doctor. But it is very risky to use any kind of medicine without prescription of a doctor.
PHARMACOLGY
Paracetamol is the formulation of Paracetamol, which is one of the safest and most widely used analgesic and antipyretic. Paracetamol produce analgesic action by elevation of the pain threshold and antipyretic through action on the hypothalamic heat regulation centre. Paracetamol exerts significantly milder side effects and most unlikely to produce many of the serious side effects associated with aspirin and other NSAIDs. Paracetamol is rapidly and completely absorbed from the G.I.T. following oral administration and from rectum after rectal administration. The mean half-life of absorption from the upper small intestine is only 7 minutes. The drug is extensively metabolized in the liver and it has a plasma half- life 1.5 to 3.0 hours. Paracetamol is not bound to plasma proteins to any extent.
INDICATION
Fever, Common cold and influenza, Headache, Toothache, Earache, Body ache, Myalgia, Dysmenorrheal, Neuralgia and Sprains. Pain of colic, back pain, post-operative pain, chronic pain of cancer, inflammatory pain and post vaccination pain and fever of children. Rheumatism and osteoarthritis pain & stiffness of joints in fingers, hips, knees, wrist, elbows, feet, ankles and top & bottom of the spine.
DOSAGE AND ADMINISTRATION
Adult : 1-2 tablets every 4 to 6 hours up to a maximum of (8 tablets) daily.
Children : (6-12) years ½ to 1 tablets 3 to 4 times daily. For long term
treatment, It is wise not to exceed the dose beyond 2.6gm/day.
SYRUP and SUSPENSION
Children Under 3 months : 10mg/kg body weight (reduce to 5 mg/kg if jaundiced)
3 to 4 times daily
3 months to below 1 year: ½ teaspoonful 3 to 4 times daily.
6-12 years : 2-4 teaspoonfuls 3 to 4 times daily.
Adults :4-8 teaspoonfuls 3 to 4 times daily.
CONTRAINDICATION
Known sensitivity to paracetamol.
SIDE EFFECTS
Side effects are significantly mild, though hematological reactions have been reported. Pancreatitis, Skin rashes and other allergic reactions occur occasionally
OVER DOSE
Moderate overdose : 4-10gm/day
Excessive overdose : More than 10mg/day.
Symptoms of overdose include pallor, nausea, vomiting, anorexia & abdominal pain. Liver damage may become apparent 12-48 hours after ingestion.
In severe poisoning hepatic failure may progress to encephalopathy, coma & DEATH.
example- Ace, Napa, Reset, Renova, Xcel
PARACETAMOL
Paracetamol is a common medicine to everybody. It is most useful and well known to everybody. All of doctors prescribe this medicine often. There is no man who does not use paracetamol. Somebody uses this medicine without suggestion of doctor. But it is very risky to use any kind of medicine without prescription of a doctor.
PHARMACOLGY
Paracetamol is the formulation of Paracetamol, which is one of the safest and most widely used analgesic and antipyretic. Paracetamol produce analgesic action by elevation of the pain threshold and antipyretic through action on the hypothalamic heat regulation centre. Paracetamol exerts significantly milder side effects and most unlikely to produce many of the serious side effects associated with aspirin and other NSAIDs. Paracetamol is rapidly and completely absorbed from the G.I.T. following oral administration and from rectum after rectal administration. The mean half-life of absorption from the upper small intestine is only 7 minutes. The drug is extensively metabolized in the liver and it has a plasma half- life 1.5 to 3.0 hours. Paracetamol is not bound to plasma proteins to any extent.
INDICATION
Fever, Common cold and influenza, Headache, Toothache, Earache, Body ache, Myalgia, Dysmenorrheal, Neuralgia and Sprains. Pain of colic, back pain, post-operative pain, chronic pain of cancer, inflammatory pain and post vaccination pain and fever of children. Rheumatism and osteoarthritis pain & stiffness of joints in fingers, hips, knees, wrist, elbows, feet, ankles and top & bottom of the spine.
DOSAGE AND ADMINISTRATION
Adult : 1-2 tablets every 4 to 6 hours up to a maximum of (8 tablets) daily.
Children : (6-12) years ½ to 1 tablets 3 to 4 times daily. For long term
treatment, It is wise not to exceed the dose beyond 2.6gm/day.
SYRUP and SUSPENSION
Children Under 3 months : 10mg/kg body weight (reduce to 5 mg/kg if jaundiced)
3 to 4 times daily
3 months to below 1 year: ½ teaspoonful 3 to 4 times daily.
6-12 years : 2-4 teaspoonfuls 3 to 4 times daily.
Adults :4-8 teaspoonfuls 3 to 4 times daily.
CONTRAINDICATION
Known sensitivity to paracetamol.
SIDE EFFECTS
Side effects are significantly mild, though hematological reactions have been reported. Pancreatitis, Skin rashes and other allergic reactions occur occasionally
OVER DOSE
Moderate overdose : 4-10gm/day
Excessive overdose : More than 10mg/day.
Symptoms of overdose include pallor, nausea, vomiting, anorexia & abdominal pain. Liver damage may become apparent 12-48 hours after ingestion.
In severe poisoning hepatic failure may progress to encephalopathy, coma & DEATH.
example- Ace, Napa, Reset, Renova, Xcel
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