Biaxin Information
Biaxin ()
Biaxin () Description
Clarithromycin is a semi-synthetic macrolide antibiotic. Chemically, it is 6--methylerythromycin. The molecular formula is CHNO, and the molecular weight is 747.96. The structural formula is:
Clarithromycin is a white to off-white crystalline powder. It is soluble in acetone, slightly soluble in methanol, ethanol, and acetonitrile, and practically insoluble in water.
Biaxin () is available as immediate-release tablets, extended-release tablets, and granules for oral suspension.
Each yellow oval film-coated immediate-release Biaxin () tablet (clarithromycin tablets, USP) contains 250 mg or 500 mg of clarithromycin and the following inactive ingredients:
250 mg tablets: hypromellose, hydroxypropyl cellulose, croscarmellose sodium, D&C Yellow No. 10, FD&C Blue No. 1, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized starch, propylene glycol, silicon dioxide, sorbic acid, sorbitan monooleate, stearic acid, talc, titanium dioxide, and vanillin.
500 mg tablets: hypromellose, hydroxypropyl cellulose, colloidal silicon dioxide, croscarmellose sodium, D&C Yellow No. 10, magnesium stearate, microcrystalline cellulose, povidone, propylene glycol, sorbic acid, sorbitan monooleate, titanium dioxide, and vanillin.
Each yellow oval film-coated Biaxin () XL tablet (clarithromycin extended-release tablets) contains 500 mg of clarithromycin and the following inactive ingredients: cellulosic polymers, D&C Yellow No. 10, lactose monohydrate, magnesium stearate, propylene glycol, sorbic acid, sorbitan monooleate, talc, titanium dioxide, and vanillin.
After constitution, each 5 mL of Biaxin () suspension (clarithromycin for oral suspension, USP) contains 125 mg or 250 mg of clarithromycin. Each bottle of Biaxin () granules contains 1250 mg (50 mL size), 2500 mg (50 and 100 mL sizes) or 5000 mg (100 mL size) of clarithromycin and the following inactive ingredients: carbomer, castor oil, citric acid, hypromellose phthalate, maltodextrin, potassium sorbate, povidone, silicon dioxide, sucrose, xanthan gum, titanium dioxide and fruit punch flavor.
Biaxin () Clinical Pharmacology
Clarithromycin is rapidly absorbed from the gastrointestinal tract after oral administration. The absolute bioavailability of 250 mg clarithromycin tablets was approximately 50%. For a single 500 mg dose of clarithromycin, food slightly delays the onset of clarithromycin absorption, increasing the peak time from approximately 2 to 2.5 hours. Food also increases the clarithromycin peak plasma concentration by about 24%, but does not affect the extent of clarithromycin bioavailability. Food does not affect the onset of formation of the antimicrobially active metabolite, 14-OH clarithromycin or its peak plasma concentration but does slightly decrease the extent of metabolite formation, indicated by an 11% decrease in area under the plasma concentration-time curve (AUC). Therefore, Biaxin () tablets may be given without regard to food.
In nonfasting healthy human subjects (males and females), peak plasma concentrations were attained within 2 to 3 hours after oral dosing. Steady-state peak plasma clarithromycin concentrations were attained within 3 days and were approximately 1 to 2 µg/mL with a 250 mg dose administered every 12 hours and 3 to 4 µg/mL with a 500 mg dose administered every 8 to 12 hours. The elimination half-life of clarithromycin was about 3 to 4 hours with 250 mg administered every 12 hours but increased to 5 to 7 hours with 500 mg administered every 8 to 12 hours. The nonlinearity of clarithromycin pharmacokinetics is slight at the recommended doses of 250 mg and 500 mg administered every 8 to 12 hours. With a 250 mg every 12 hours dosing, the principal metabolite, 14-OH clarithromycin, attains a peak steady-state concentration of about 0.6 µg/mL and has an elimination half-life of 5 to 6 hours. With a 500 mg every 8 to 12 hours dosing, the peak steady-state concentration of 14-OH clarithromycin is slightly higher (up to 1 µg/mL), and its elimination half-life is about 7 to 9 hours. With any of these dosing regimens, the steady-state concentration of this metabolite is generally attained within 3 to 4 days.
After a 250 mg tablet every 12 hours, approximately 20% of the dose is excreted in the urine as clarithromycin, while after a 500 mg tablet every 12 hours, the urinary excretion of clarithromycin is somewhat greater, approximately 30%. In comparison, after an oral dose of 250 mg (125 mg/5 mL) suspension every 12 hours, approximately 40% is excreted in urine as clarithromycin. The renal clearance of clarithromycin is, however, relatively independent of the dose size and approximates the normal glomerular filtration rate. The major metabolite found in urine is 14-OH clarithromycin, which accounts for an additional 10% to 15% of the dose with either a 250 mg or a 500 mg tablet administered every 12 hours.
Steady-state concentrations of clarithromycin and 14-OH clarithromycin observed following administration of 500 mg doses of clarithromycin every 12 hours to adult patients with HIV infection were similar to those observed in healthy volunteers. In adult HIV-infected patients taking 500- or 1000-mg doses of clarithromycin every 12 hours, steady-state clarithromycin C values ranged from 2 to 4 µg/mL and 5 to 10 µg/mL, respectively.
The steady-state concentrations of clarithromycin in subjects with impaired hepatic function did not differ from those in normal subjects; however, the 14-OH clarithromycin concentrations were lower in the hepatically impaired subjects. The decreased formation of 14-OH clarithromycin was at least partially offset by an increase in renal clearance of clarithromycin in the subjects with impaired hepatic function when compared to healthy subjects.
The pharmacokinetics of clarithromycin was also altered in subjects with impaired renal function. (See and .)
Clarithromycin and the 14-OH clarithromycin metabolite distribute readily into body tissues and fluids. There are no data available on cerebrospinal fluid penetration. Because of high intracellular concentrations, tissue concentrations are higher than serum concentrations. Examples of tissue and serum concentrations are presented below.
Clarithromycin extended-release tablets provide extended absorption of clarithromycin from the gastrointestinal tract after oral administration. Relative to an equal total daily dose of immediate-release clarithromycin tablets, clarithromycin extended-release tablets provide lower and later steady-state peak plasma concentrations but equivalent 24-hour AUC's for both clarithromycin and its microbiologically-active metabolite, 14-OH clarithromycin. While the extent of formation of 14-OH clarithromycin following administration of Biaxin () XL tablets (2 x 500 mg once daily) is not affected by food, administration under fasting conditions is associated with approximately 30% lower clarithromycin AUC relative to administration with food. Therefore, Biaxin () XL tablets should be taken with food.
Steady-State Clarithromycin Plasma Concentration-Time Profiles
In healthy human subjects, steady-state peak plasma clarithromycin concentrations of approximately 2 to 3 µg/mL were achieved about 5 to 8 hours after oral administration of 2 x 500 mg Biaxin () XL tablets once daily; for 14-OH clarithromycin, steady-state peak plasma concentrations of approximately 0.8 µg/mL were attained about 6 to 9 hours after dosing. Steady-state peak plasma clarithromycin concentrations of approximately 1 to 2 µg/mL were achieved about 5 to 6 hours after oral administration of a single 500 mg Biaxin () XL tablet once daily; for 14-OH clarithromycin, steady-state peak plasma concentrations of approximately 0.6 µg/mL were attained about 6 hours after dosing.
When 250 mg doses of clarithromycin as Biaxin () suspension were administered to fasting healthy adult subjects, peak plasma concentrations were attained around 3 hours after dosing. Steady-state peak plasma concentrations were attained in 2 to 3 days and were approximately 2 µg/mL for clarithromycin and 0.7 µg/mL for 14-OH clarithromycin when 250-mg doses of the clarithromycin suspension were administered every 12 hours. Elimination half-life of clarithromycin (3 to 4 hours) and that of 14-OH clarithromycin (5 to 7 hours) were similar to those observed at steady state following administration of equivalent doses of Biaxin () tablets.
For adult patients, the bioavailability of 10 mL of the 125 mg/5 mL suspension or 10 mL of the 250 mg/5 mL suspension is similar to a 250 mg or 500 mg tablet, respectively.
In children requiring antibiotic therapy, administration of 7.5 mg/kg q12h doses of clarithromycin as the suspension generally resulted in steady-state peak plasma concentrations of 3 to 7 µg/mL for clarithromycin and 1 to 2 µg/mL for 14-OH clarithromycin.
In HIV-infected children taking 15 mg/kg every 12 hours, steady-state clarithromycin peak concentrations generally ranged from 6 to 15 µg/mL.
Clarithromycin penetrates into the middle ear fluid of children with secretory otitis media.
In adults given 250 mg clarithromycin as suspension (n = 22), food appeared to decrease mean peak plasma clarithromycin concentrations from 1.2 (± 0.4) µg/mL to 1.0 (± 0.4) µg/mL and the extent of absorption from 7.2 (± 2.5) hrµg/mL to 6.5 (± 3.7) hrµg/mL.
When children (n = 10) were administered a single oral dose of 7.5 mg/kg suspension, food increased mean peak plasma clarithromycin concentrations from 3.6 (± 1.5) µg/mL to 4.6 (± 2.8) µg/mL and the extent of absorption from 10.0 (± 5.5) hrµg/mL to 14.2 (± 9.4) hrµg/mL.
Clarithromycin 500 mg every 8 hours was given in combination with omeprazole 40 mg daily to healthy adult males. The plasma levels of clarithromycin and 14-hydroxy-clarithromycin were increased by the concomitant administration of omeprazole. For clarithromycin, the mean C was 10% greater, the mean C was 27% greater, and the mean AUC was 15% greater when clarithromycin was administered with omeprazole than when clarithromycin was administered alone. Similar results were seen for 14-hydroxy-clarithromycin, the mean C was 45% greater, the mean C was 57% greater, and the mean AUCwas 45% greater. Clarithromycin concentrations in the gastric tissue and mucus were also increased by concomitant administration of omeprazole.
For information about other drugs indicated in combination with Biaxin () , refer to the section of their package inserts.
Clarithromycin exerts its antibacterial action by binding to the 50S ribosomal subunit of susceptible microorganisms resulting in inhibition of protein synthesis.
Clarithromycin is active against a variety of aerobic and anaerobic gram-positive and gram-negative microorganisms as well as most complex (MAC) microorganisms.
Additionally, the 14-OH clarithromycin metabolite also has clinically significant antimicrobial activity. The 14-OH clarithromycin is twice as active against microorganisms as the parent compound. However, for complex (MAC) isolates the 14-OH metabolite is 4 to 7 times less active than clarithromycin. The clinical significance of this activity against complex is unknown.
Clarithromycin has been shown to be active against most strains of the following microorganisms both and in clinical infections as described in the section:
Biaxin () Indications And Usage
Biaxin () Filmtab (clarithromycin tablets, USP) and Biaxin () Granules (clarithromycin for oral suspension, USP) are indicated for the treatment of mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions as listed below:
Pharyngitis/Tonsillitis due to (The usual drug of choice in the treatment and prevention of streptococcal infections and the prophylaxis of rheumatic fever is penicillin administered by either the intramuscular or the oral route. Clarithromycin is generally effective in the eradication of from the nasopharynx; however, data establishing the efficacy of clarithromycin in the subsequent prevention of rheumatic fever are not available at present).
Acute maxillary sinusitis due to , , or .
Acute bacterial exacerbation of chronic bronchitis due to , , , or .
Community-Acquired Pneumonia due to , , , or (TWAR).
Uncomplicated skin and skin structure infections due to , or (Abscesses usually require surgical drainage).
Disseminated mycobacterial infections due to , or
Biaxin () (clarithromycin) Filmtab tablets in combination with amoxicillin and PREVACID (lansoprazole) or PRILOSEC (omeprazole) Delayed-Release Capsules, as triple therapy, are indicated for the treatment of patients with infection and duodenal ulcer disease (active or five-year history of duodenal ulcer) to eradicate .
Biaxin () Filmtab tablets in combination with PRILOSEC (omeprazole) capsules or TRITEC (ranitidine bismuth citrate) tablets are also indicated for the treatment of patients with an active duodenal ulcer associated with infection. However, regimens which contain clarithromycin as the single antimicrobial agent are more likely to be associated with the development of clarithromycin resistance among patients who fail therapy. Clarithromycin-containing regimens should not be used in patients with known or suspected clarithromycin resistant isolates because the efficacy of treatment is reduced in this setting.
In patients who fail therapy, susceptibility testing should be done if possible. If resistance to clarithromycin is demonstrated, a non-clarithromycin-containing therapy is recommended. (For information on development of resistance see section.) The eradication of has been demonstrated to reduce the risk of duodenal ulcer recurrence.
Pharyngitis/Tonsillitis due to .
Community-Acquired Pneumonia due to , , or (TWAR)
Acute maxillary sinusitis due to , , or
Acute otitis media due to , , or
Uncomplicated skin and skin structure infections due to , or (Abscesses usually require surgical drainage.)
Disseminated mycobacterial infections due to , or
Biaxin () XL Filmtab (clarithromycin extended-release tablets) are indicated for the treatment of adults with mild to moderate infection caused by susceptible strains of the designated microorganisms in the conditions listed below:
Acute maxillary sinusitis due to , , or
Acute bacterial exacerbation of chronic bronchitis due to , , , or
Community-Acquired Pneumonia due to , , , , (TWAR), or
THE EFFICACY AND SAFETY OF Biaxin () XL IN TREATING OTHER INFECTIONS FOR WHICH OTHER FORMULATIONS OF Biaxin () ARE APPROVED HAVE NOT BEEN ESTABLISHED.
Biaxin () Filmtab tablets and Biaxin () Granules for oral suspension are indicated for the prevention of disseminated complex (MAC) disease in patients with advanced HIV infection.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Biaxin () and other antibacterial drugs, Biaxin () should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Biaxin () Contraindications
Clarithromycin is contraindicated in patients with a known hypersensitivity to clarithromycin or any of its excipients, erythromycin, or any of the macrolide antibiotics.
Clarithromycin is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of clarithromycin.
Concomitant administration of clarithromycin and any of the following drugs is contraindicated: cisapride, pimozide, astemizole, terfenadine, and ergotamine or dihydroergotamine (see ). There have been post-marketing reports of drug interactions when clarithromycin and/or erythromycin are coadministered with cisapride, pimozide, astemizole, or terfenadine resulting in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de pointes) most likely due to inhibition of metabolism of these drugs by erythromycin and clarithromycin. Fatalities have been reported.
Concomitant administration of clarithromycin and colchicine is contraindicated in patients with renal or hepatic impairment.
Clarithromycin should not be given to patients with history of QT prolongation or ventricular cardiac arrhythmia, including .
Clarithromycin should not be used concomitantly with HMG-CoA reductase inhibitors (statins), lovastatin or simvastatin, due to the risk of rhabdomyolysis. Treatment with these agents should be discontinued during clarithromycin treatment ().
For information about contraindications of other drugs indicated in combination with Biaxin () , refer to the section of their package inserts.
Biaxin () Warnings
p36115924
CLARITHROMYCIN SHOULD NOT BE USED IN PREGNANT WOMEN EXCEPT IN CLINICAL CIRCUMSTANCES WHERE NO ALTERNATIVE THERAPY IS APPROPRIATE. IF PREGNANCY OCCURS WHILE TAKING THIS DRUG, THE PATIENT SHOULD BE APPRISED OF THE POTENTIAL HAZARD TO THE FETUS. CLARITHROMYCIN HAS DEMONSTRATED ADVERSE EFFECTS OF PREGNANCY OUTCOME AND/OR EMBRYO-FETAL DEVELOPMENT IN MONKEYS, RATS, MICE, AND RABBITS AT DOSES THAT PRODUCED PLASMA LEVELS 2 TO 17 TIMES THE SERUM LEVELS ACHIEVED IN HUMANS TREATED AT THE MAXIMUM RECOMMENDED HUMAN DOSES. (See PRECAUTIONS -
.)
Serious adverse reactions have been reported in patients taking clarithromycin concomitantly with CYP3A4 substrates. These include colchicine toxicity with colchicine; rhabdomyolysis with simvastatin, lovastatin, and atorvastatin; and hypotension with calcium channel blockers metabolized by CYP3A4 (e.g., verapamil, amlodipine, diltiazem) (see and ).
Life-threatening and fatal drug interactions have been reported in patients treated with clarithromycin and colchicine. Clarithromycin is a strong CYP3A4 inhibitor and this interaction may occur while using both drugs at their recommended doses. If co-administration of clarithromycin and colchicine is necessary in patients with normal renal and hepatic function, the dose of colchicine should be reduced. Patients should be monitored for clinical symptoms of colchicine toxicity. Concomitant administration of clarithromycin and colchicine is contraindicated in patients with renal or hepatic impairment (see and ).
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of , and surgical evaluation should be instituted as clinically indicated.
For information about warnings of other drugs indicated in combination with Biaxin () , refer to the section of their package inserts.
Due to the risk for QT prolongation clarithromycin should be used with caution in patients with a medical condition associated with an increased tendency toward QT prolongation and .
In the event of severe acute hypersensitivity reactions, such as anaphylaxis, Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS), and Henoch-Schonlein purpura clarithromycin therapy should be discontinued immediately and appropriate treatment should be urgently initiated.
Biaxin () Precautions
Prescribing Biaxin () in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Clarithromycin is principally excreted via the liver and kidney. Clarithromycin may be administered without dosage adjustment to patients with hepatic impairment and normal renal function. However, in the presence of severe renal impairment with or without coexisting hepatic impairment, decreased dosage or prolonged dosing intervals may be appropriate.
Clarithromycin in combination with ranitidine bismuth citrate therapy is not recommended in patients with creatinine clearance less than 25 mL/min. (See .)
Clarithromycin in combination with ranitidine bismuth citrate should not be used in patients with a history of acute porphyria.
Exacerbation of symptoms of myasthenia gravis and new onset of symptoms of myasthenic syndrome has been reported in patients receiving clarithromycin therapy.
For information about precautions of other drugs indicated in combination with Biaxin () , refer to the section of their package inserts.
Patients should be counseled that antibacterial drugs including Biaxin () should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Biaxin () is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Biaxin () or other antibacterial drugs in the future.
Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.
Biaxin () may interact with some drugs; therefore patients should be advised to report to their doctor the use of any other medications.
Biaxin () tablets and oral suspension can be taken with or without food and can be taken with milk; however, Biaxin () XL tablets should be taken with food. Do refrigerate the suspension.
Clarithromycin use in patients who are receiving theophylline may be associated with an increase of serum theophylline concentrations. Monitoring of serum theophylline concentrations should be considered for patients receiving high doses of theophylline or with baseline concentrations in the upper therapeutic range. In two studies in which theophylline was administered with clarithromycin (a theophylline sustained-release formulation was dosed at either 6.5 mg/kg or 12 mg/kg together with 250 or 500 mg q12h clarithromycin), the steady-state levels of C, C, and the area under the serum concentration time curve (AUC) of theophylline increased about 20%.
Hypotension, bradyarrhythmias, and lactic acidosis have been observed in patients receiving concurrent verapamil, belonging to the calcium channel blockers drug class.
Concomitant administration of single doses of clarithromycin and carbamazepine has been shown to result in increased plasma concentrations of carbamazepine. Blood level monitoring of carbamazepine may be considered.
When clarithromycin and terfenadine were coadministered, plasma concentrations of the active acid metabolite of terfenadine were threefold higher, on average, than the values observed when terfenadine was administered alone. The pharmacokinetics of clarithromycin and the 14-OH-clarithromycin were not significantly affected by coadministration of terfenadine once clarithromycin reached steady-state conditions. Concomitant administration of clarithromycin with terfenadine is contraindicated. (See .)
Clarithromycin 500 mg every 8 hours was given in combination with omeprazole 40 mg daily to healthy adult subjects. The steady-state plasma concentrations of omeprazole were increased (C, AUC, and t increases of 30%, 89%, and 34%, respectively), by the concomitant administration of clarithromycin. The mean 24-hour gastric pH value was 5.2 when omeprazole was administered alone and 5.7 when coadministered with clarithromycin.
Coadministration of clarithromycin with ranitidine bismuth citrate resulted in increased plasma ranitidine concentrations (57%), increased plasma bismuth trough concentrations (48%), and increased 14-hydroxy-clarithromycin plasma concentrations (31%). These effects are clinically insignificant.
Simultaneous oral administration of Biaxin () tablets and zidovudine to HIV-infected adult patients may result in decreased steady-state zidovudine concentrations. Following administration of clarithromycin 500 mg tablets twice daily with zidovudine 100 mg every 4 hours, the steady-state zidovudine AUC decreased 12% compared to administration of zidovudine alone (n=4). Individual values ranged from a decrease of 34% to an increase of 14%. When clarithromycin tablets were administered two to four hours prior to zidovudine, the steady-state zidovudine C increased 100% whereas the AUC was unaffected (n=24). Administration of clarithromycin and zidovudine should be separated by at least two hours. The impact of co-administration of clarithromycin extended-release tablets and zidovudine has not been evaluated.
Simultaneous administration of Biaxin () tablets and didanosine to 12 HIV-infected adult patients resulted in no statistically significant change in didanosine pharmacokinetics.
Following administration of fluconazole 200 mg daily and clarithromycin 500 mg twice daily to 21 healthy volunteers, the steady-state clarithromycin C and AUC increased 33% and 18%, respectively. Steady-state concentrations of 14-OH clarithromycin were not significantly affected by concomitant administration of fluconazole. No dosage adjustment of clarithromycin is necessary when co-administered with fluconazole.
The following mutagenicity tests have been conducted with clarithromycin:
Salmonella
Bacterial Induced Mutation Frequency Test
In Vitro
Rat Hepatocyte DNA Synthesis Assay
Mouse Lymphoma Assay
Mouse Dominant Lethal Study
Mouse Micronucleus Test
All tests had negative results except the Chromosome Aberration Test which was weakly positive in one test and negative in another.
In addition, a Bacterial Reverse-Mutation Test (Ames Test) has been performed on clarithromycin metabolites with negative results.
Fertility and reproduction studies have shown that daily doses of up to 160 mg/kg/day (1.3 times the recommended maximum human dose based on mg/m) to male and female rats caused no adverse effects on the estrous cycle, fertility, parturition, or number and viability of offspring. Plasma levels in rats after 150 mg/kg/day were 2 times the human serum levels.
In the 150 mg/kg/day monkey studies, plasma levels were 3 times the human serum levels. When given orally at 150 mg/kg/day (2.4 times the recommended maximum human dose based on mg/m), clarithromycin was shown to produce embryonic loss in monkeys. This effect has been attributed to marked maternal toxicity of the drug at this high dose.
In rabbits, fetal loss occurred at an intravenous dose of 33 mg/m, which is 17 times less than the maximum proposed human oral daily dose of 618 mg/m.
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of clarithromycin.
Biaxin () Adverse Reactions
The majority of side effects observed in clinical trials were of a mild and transient nature. Fewer than 3% of adult patients without mycobacterial infections and fewer than 2% of pediatric patients without mycobacterial infections discontinued therapy because of drug-related side effects. Fewer than 2% of adult patients taking Biaxin () XL tablets discontinued therapy because of drug-related side effects.
The most frequently reported events in adults taking Biaxin () tablets (clarithromycin tablets, USP) were diarrhea (3%), nausea (3%), abnormal taste (3%), dyspepsia (2%), abdominal pain/discomfort (2%), and headache (2%). In pediatric patients, the most frequently reported events were diarrhea (6%), vomiting (6%), abdominal pain (3%), rash (3%), and headache (2%). Most of these events were described as mild or moderate in severity. Of the reported adverse events, only 1% was described as severe.
The most frequently reported events in adults taking Biaxin () XL (Clarithromycin extended-release tablets) were diarrhea (6%), abnormal taste (7%), and nausea (3%). Most of these events were described as mild or moderate in severity. Of the reported adverse events, less than 1% were described as severe.
In the acute exacerbation of chronic bronchitis and acute maxillary sinusitis studies overall gastrointestinal adverse events were reported by a similar proportion of patients taking either Biaxin () tablets or Biaxin () XL tablets; however, patients taking Biaxin () XL tablets reported significantly less severe gastrointestinal symptoms compared to patients taking Biaxin () tablets. In addition, patients taking Biaxin () XL tablets had significantly fewer premature discontinuations for drug-related gastrointestinal or abnormal taste adverse events compared to Biaxin () tablets.
In community-acquired pneumonia studies conducted in adults comparing clarithromycin to erythromycin base or erythromycin stearate, there were fewer adverse events involving the digestive system in clarithromycin-treated patients compared to erythromycin-treated patients (13% vs 32%; p
In two U.S. studies of acute otitis media comparing clarithromycin to amoxicillin/potassium clavulanate in pediatric patients, there were fewer adverse events involving the digestive system in clarithromycin-treated patients compared to amoxicillin/potassium clavulanate-treated patients (21% vs. 40%, p
Biaxin () Overdosage
Overdosage of clarithromycin can cause gastrointestinal symptoms such as abdominal pain, vomiting, nausea, and diarrhea.
Adverse reactions accompanying overdosage should be treated by the prompt elimination of unabsorbed drug and supportive measures. As with other macrolides, clarithromycin serum concentrations are not expected to be appreciably affected by hemodialysis or peritoneal dialysis.
Biaxin () Dosage And Administration
Biaxin () Filmtab (clarithromycin tablets, USP) and Biaxin () Granules (clarithromycin for oral suspension, USP) may be given with or without food. Biaxin () XL Filmtab (clarithromycin extended-release tablets) should be taken with food. Biaxin () XL tablets should be swallowed whole and not chewed, broken or crushed.
Clarithromycin may be administered without dosage adjustment in the presence of hepatic impairment if there is normal renal function. In patients with severe renal impairment (CL
Biaxin () How Supplied
Biaxin () Filmtab (clarithromycin tablets, USP) are supplied as yellow oval film-coated tablets in the following packaging sizes:
250 mg tablets: (imprinted in blue with the Abbott logo and Abbo-Code KT)
Bottles of 60 ( 0074-3368-60) and ABBO-PAC unit dose strip packages of 100 ( 0074-3368-11).
Store Biaxin () 250 mg tablets at controlled room temperature 15° to 30°C (59° to 86°F) in a well-closed container. Protect from light.
500 mg tablets: (debossed with the Abbott logo on one side and Abbo-Code KL on the opposite side)
Bottles of 60 ( 0074-2586-60) and ABBO-PAC unit dose strip packages of 100 ( 0074-2586-11).
Store Biaxin () 500 mg tablets at controlled room temperature 20° to 25°C (68° to 77°F) in a well-closed container.
Biaxin () XL Filmtab (clarithromycin extended-release tablets) are supplied as yellow oval film-coated 500 mg tablets debossed (on one side) with the Abbott logo and a two-letter Abbo-Code designation, KJ in the following packaging sizes:
500 mg tablets:
Bottles of 60 (NDC 0074-3165-60), ABBO-PAC unit dose strip packages of 100 ( 0074-3165-11), and Biaxin () XL PAC carton of 4 blister packages 14 tablets each ( 0074-3165-41).
Store Biaxin () XL tablets at 20° to 25°C (68° to 77°F). Excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.]
Biaxin () Granules (clarithromycin for oral suspension, USP) is supplied in the following strengths and sizes:
Store Biaxin () granules for oral suspension at controlled room temperature 15° to 30°C (59° to 86°F) in a well-closed container. Do not refrigerate Biaxin () suspension.
Biaxin () Clinical Studies
In a controlled clinical study of acute otitis media performed in the United States, where significant rates of beta-lactamase producing organisms were found, clarithromycin was compared to an oral cephalosporin. In this study, very strict evaluability criteria were used to determine clinical response. For the 223 patients who were evaluated for clinical efficacy, the clinical success rate (i.e., cure plus improvement) at the post-therapy visit was 88% for clarithromycin and 91% for the cephalosporin.
In a smaller number of patients, microbiologic determinations were made at the pre-treatment visit. The following presumptive bacterial eradication/clinical cure outcomes (i.e., clinical success) were obtained:
Biaxin () Animal Pharmacology And Toxicology
Clarithromycin is rapidly and well-absorbed with dose-linear kinetics, low protein binding, and a high volume of distribution. Plasma half-life ranged from 1 to 6 hours and was species dependent. High tissue concentrations were achieved, but negligible accumulation was observed. Fecal clearance predominated. Hepatotoxicity occurred in all species tested (i.e., in rats and monkeys at doses 2 times greater than and in dogs at doses comparable to the maximum human daily dose, based on mg/m). Renal tubular degeneration (calculated on a mg/m basis) occurred in rats at doses 2 times, in monkeys at doses 8 times, and in dogs at doses 12 times greater than the maximum human daily dose. Testicular atrophy (on a mg/m basis) occurred in rats at doses 7 times, in dogs at doses 3 times, and in monkeys at doses 8 times greater than the maximum human daily dose. Corneal opacity (on a mg/m basis) occurred in dogs at doses 12 times and in monkeys at doses 8 times greater than the maximum human daily dose. Lymphoid depletion (on a mg/m basis) occurred in dogs at doses 3 times greater than and in monkeys at doses 2 times greater than the maximum human daily dose. These adverse events were absent during clinical trials.
Biaxin ()
Biaxin ()
