BIAXIN Filmtab (Tablet, Film Coated)

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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.<br/>H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence:<br/>Triple therapy: BIAXIN/lansoprazole/amoxicillin: The recommended adult dose is 500 mg BIAXIN, 30 mg lansoprazole, and 1 gram amoxicillin, all given twice daily (q12h) for 10 or 14 days. (See INDICATIONS AND USAGE and CLINICAL STUDIES sections.)<br/>Triple therapy: BIAXIN/omeprazole/amoxicillin: The recommended adult dose is 500 mg BIAXIN, 20 mg omeprazole, and 1 gram amoxicillin, all given twice daily (q12h) for 10 days. (See INDICATIONS AND USAGE and CLINICAL STUDIES sections.) In patients with an ulcer present at the time of initiation of therapy, an additional 18 days of omeprazole 20 mg once daily is recommended for ulcer healing and symptom relief.<br/>Dual therapy: BIAXIN/omeprazole: The recommended adult dose is 500 mg BIAXIN given three times daily (q8h) and 40 mg omeprazole given once daily (qAM) for 14 days. (See INDICATIONS AND USAGE and CLINICAL STUDIES sections.) An additional 14 days of omeprazole 20 mg once daily is recommended for ulcer healing and symptom relief.<br/>Dual therapy: BIAXIN/ranitidine bismuth citrate: The recommended adult dose is 500 mg BIAXIN given twice daily (q12h) or three times daily (q8h) and 400 mg ranitidine bismuth citrate given twice daily (q12h) for 14 days. An additional 14 days of 400 mg twice daily is recommended for ulcer healing and symptom relief. BIAXIN and ranitidine bismuth citrate combination therapy is not recommended in patients with creatinine clearance less than 25 mL/min. (See INDICATIONS AND USAGE and CLINICAL STUDIES sections.)<br/>Children: The usual recommended daily dosage is 15 mg/kg/day divided q12h for 10 days. Clarithromycin may be administered without dosage adjustment in the presence of hepatic impairment if there is normal renal function. However, in the presence of severe renal impairment (CR<30 mL/min), with or without coexisting hepatic impairment, the dose should be halved or the dosing interval doubled.<br/>Mycobacterial Infections:<br/>Prophylaxis: The recommended dose of BIAXIN for the prevention of disseminated Mycobacterium avium disease is 500 mg b.i.d. In children, the recommended dose is 7.5 mg/kg b.i.d. up to 500 mg b.i.d. No studies of clarithromycin for MAC prophylaxis have been performed in pediatric populations and the doses recommended for prophylaxis are derived from MAC treatment studies in children. Dosing recommendations for children are in the table above.<br/>Treatment: Clarithromycin is recommended as the primary agent for the treatment of disseminated infection due to Mycobacterium avium complex. Clarithromycin should be used in combination with other antimycobacterial drugs that have shown in vitro activity against MAC or clinical benefit in MAC treatment. (See CLINICAL STUDIES.) The recommended dose for mycobacterial infections in adults is 500 mg b.i.d. In children, the recommended dose is 7.5 mg/kg b.i.d. up to 500 mg b.i.d. Dosing recommendations for children are in the table above. Clarithromycin therapy should continue for life if clinical and mycobacterial improvements are observed.<br/>Constituting Instructions: The table below indicates the volume of water to be added when constituting: Add half the volume of water to the bottle and shake vigorously. Add the remainder of water to the bottle and shake. Shake well before each use. Oversize bottle provides shake space. Keep tightly closed. Do not refrigerate. After mixing, store at 15��to 30��C (59��to 86��F) and use within 14 days.

Pharmacokinetics: 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��g/mL with a 250 mg dose administered every 12 hours and 3 to 4��g/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��g/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��g/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 Cvalues ranged from 2 to 4��g/mL and 5 to 10��g/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 PRECAUTIONS and DOSAGE AND ADMINISTRATION.) 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-OHclarithromycin 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. In healthy human subjects, steady-state peak plasma clarithromycin concentrations of approximately 2 to 3��g/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��g/mL were attained about 6 to 9 hours after dosing. Steady-state peak plasma clarithromycin concentrations of approximately 1 to 2��g/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��g/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��g/mL for clarithromycin and 0.7��g/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��g/mL for clarithromycin and 1 to 2��g/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��g/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)��g/mL to 1.0 (��0.4)��g/mL and the extent of absorption from 7.2 (��2.5) hr�����g/mL to 6.5 (��3.7) hr�����g/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)��g/mL to 4.6 (��2.8)��g/mL and the extent of absorption from 10.0 (��5.5) hr�����g/mL to 14.2 (��9.4) hr�����g/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 Cwas 10% greater, the mean Cwas 27% greater, and the mean AUCwas 15% greater when clarithromycin was administered with omeprazole than when clarithromycin was administered alone. Similar results were seen for 14-hydroxy-clarithromycin, the mean Cwas 45% greater, the mean Cwas 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 CLINICAL PHARMACOLOGY section of their package inserts.<br/>Microbiology: Clarithromycin exerts its antibacterial action by binding to the 50S ribosomal subunit of susceptible microorganisms resulting in inhibition of protein synthesis. Clarithromycin is active in vitro against a variety of aerobic and anaerobic gram-positive and gram-negative microorganisms as well as most Mycobacterium avium complex (MAC) microorganisms. Additionally, the 14-OH clarithromycin metabolite also has clinically significant antimicrobial activity. The 14-OH clarithromycin is twice as active against Haemophilus influenzae microorganisms as the parent compound. However, for Mycobacterium avium complex (MAC) isolates the 14-OH metabolite is 4 to 7 times less active than clarithromycin. The clinical significance of this activity against Mycobacterium avium complex is unknown. Clarithromycin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:<br/>Aerobic Gram-positive Microorganisms: Staphylococcus aureusStreptococcus pneumoniaeStreptococcus pyogenes<br/>Aerobic Gram-negative Microorganisms: Haemophilus influenzaeHaemophilus parainfluenzaeMoraxella catarrhalis<br/>Other Microorganisms: Mycoplasma pneumoniaeChlamydia pneumoniae (TWAR)<br/>Mycobacteria: Mycobacterium avium complex (MAC) consisting of:Mycobacterium aviumMycobacterium intracellulare Beta-lactamase production should have no effect on clarithromycin activity. NOTE: Most strains of methicillin-resistant and oxacillin-resistant staphylococci are resistant to clarithromycin. Omeprazole/clarithromycin dual therapy; ranitidine bismuth citrate/clarithromycin dual therapy; omeprazole/clarithromycin/amoxicillin triple therapy; and lansoprazole/clarithromycin/amoxicillin triple therapy have been shown to be active against most strains of Helicobacter pylori in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.<br/>Helicobacter: Helicobacter pylori<br/>Pretreatment Resistance: Clarithromycin pretreatment resistance rates were 3.5% (4/113) in the omeprazole/clarithromycin dual therapy studies (M93-067, M93-100) and 9.3% (41/439) in the omeprazole/clarithromycin/amoxicillin triple therapy studies (126, 127, M96-446). Clarithromycin pretreatment resistance was 12.6% (44/348) in the ranitidine bismuth citrate/clarithromycin b.i.d. versus t.i.d. clinical study (H2BA3001). Clarithromycin pretreatment resistance rates were 9.5% (91/960) by E-test and 11.3% (12/106) by agar dilution in the lansoprazole/clarithromycin/amoxicillin triple therapy clinical trials (M93-125, M93-130, M93-131, M95-392, and M95-399). Amoxicillin pretreatment susceptible isolates (<0.25��g/mL) were found in 99.3% (436/439) of the patients in the omeprazole/clarithromycin/amoxicillin clinical studies (126, 127, M96-446). Amoxicillin pretreatment minimum inhibitory concentrations (MICs)>0.25��g/mL occurred in 0.7% (3/439) of the patients, all of whom were in the clarithromycin/amoxicillin study arm. Amoxicillin pretreatment susceptible isolates (<0.25��g/mL) occurred in 97.8% (936/957) and 98.0% (98/100) of the patients in the lansoprazole/clarithromycin/amoxicillin triple-therapy clinical trials by E-test and agar dilution, respectively. Twenty-one of the 957 patients (2.2%) by E-test and 2 of 100 patients (2.0%) by agar dilution had amoxicillin pretreatment MICs of>0.25��g/mL. Two patients had an unconfirmed pretreatment amoxicillin minimum inhibitory concentration (MIC) of>256��g/mL by E-test. Patients not eradicated of H. pylori following omeprazole/clarithromycin, ranitidine bismuth citrate/clarithromycin, omeprazole/clarithromycin/amoxicillin, or lansoprazole/clarithromycin/ amoxicillin therapy would likely have clarithromycin resistant H. pylori isolates. Therefore, for patients who fail therapy, clarithromycin susceptibility testing should be done, if possible. Patients with clarithromycin resistant H. pylori should not be treated with any of the following: omeprazole/clarithromycin dual therapy; ranitidine bismuth citrate/clarithromycin dual therapy; omeprazole/clarithromycin/amoxicillin triple therapy; lansoprazole/clarithromycin/amoxicillin triple therapy; or other regimens which include clarithromycin as the sole antimicrobial agent.<br/>Amoxicillin Susceptibility Test Results and Clinical/Bacteriological Outcomes: In the omeprazole/clarithromycin/amoxicillin triple-therapy clinical trials, 84.9% (157/185) of the patients who had pretreatment amoxicillin susceptible MICs (<0.25��g/mL) were eradicated of H. pylori and 15.1% (28/185) failed therapy. Of the 28 patients who failed triple therapy, 11 had no post-treatment susceptibility test results, and 17 had post-treatment H. pylori isolates with amoxicillin susceptible MICs. Eleven of the patients who failed triple therapy also had post-treatment H. pylori isolates with clarithromycin resistant MICs. In the lansoprazole/clarithromycin/amoxicillin triple-therapy clinical trials, 82.6% (195/236) of the patients that had pretreatment amoxicillin susceptible MICs (<0.25��g/mL) were eradicated of H. pylori. Of those with pretreatment amoxicillin MICs of>0.25��g/mL, three of six had the H. pylori eradicated. A total of 12.8% (22/172) of the patients failed the 10- and 14-day triple-therapy regimens. Post-treatment susceptibility results were not obtained on 11 of the patients who failed therapy. Nine of the 11 patients with amoxicillin post-treatment MICs that failed the triple-therapy regimen also had clarithromycin resistant H. pylori isolates. The following in vitro data are available, but their clinical significance is unknown. Clarithromycin exhibits in vitro activity against most strains of the following microorganisms; however, the safety and effectiveness of clarithromycin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.<br/>Susceptibility Testing Excluding Mycobacteria and Helicobacter:<br/>In vitro Activity of Clarithromycin against Mycobacteria: Clarithromycin has demonstrated in vitro activity against Mycobacterium avium complex (MAC) microorganisms isolated from both AIDS and non-AIDS patients. While gene probe techniques may be used to distinguish M. avium species from M. intracellulare, many studies only reported results on M. avium complex (MAC) isolates. Various in vitro methodologies employing broth or solid media at different pH's, with and without oleic acid-albumin-dextrose-catalase (OADC), have been used to determine clarithromycin MIC values for mycobacterial species. In general, MIC values decrease more than 16-fold as the pH of Middlebrook 7H12 broth media increases from 5.0 to 7.4. At pH 7.4, MIC values determined with Mueller-Hinton agar were 4- to 8-fold higher than those observed with Middlebrook 7H12 media. Utilization of oleic acid-albumin-dextrose-catalase (OADC) in these assays has been shown to further alter MIC values. Clarithromycin activity against 80 MAC isolates from AIDS patients and 211 MAC isolates from non-AIDS patients was evaluated using a microdilution method with Middlebrook 7H9 broth. Results showed an MIC value of���4.0��g/mL in 81% and 89% of the AIDS and non-AIDS MAC isolates, respectively. Twelve percent of the non-AIDS isolates had an MIC value���0.5��g/mL. Clarithromycin was also shown to be active against phagocytized M. avium complex (MAC) in mouse and human macrophage cell cultures as well as in the beige mouse infection model. Clarithromycin activity was evaluated against Mycobacterium tuberculosis microorganisms. In one study utilizing the agar dilution method with Middlebrook 7H10 media, 3 of 30 clinical isolates had an MIC of 2.5��g/mL. Clarithromycin inhibited all isolates at>10.0��g/mL.<br/>Susceptibility Testing for Mycobacterium avium Complex (MAC): The disk diffusion and dilution techniques for susceptibility testing against gram-positive and gram-negative bacteria should not be used for determining clarithromycin MIC values against mycobacteria. In vitro susceptibility testing methods and diagnostic products currently available for determining minimum inhibitory concentration (MIC) values against Mycobacterium avium complex (MAC) organisms have not been standardized or validated. Clarithromycin MIC values will vary depending on the susceptibility testing method employed, composition and pH of the media, and the utilization of nutritional supplements. Breakpoints to determine whether clinical isolates of M. avium or M. intracellulare are susceptible or resistant to clarithromycin have not been established.<br/>Susceptibility Test for Helicobacter pylori: The reference methodology for susceptibility testing of H. pylori is agar dilution MICs.One to three microliters of an inoculum equivalent to a No. 2 McFarland standard (1 x 10-1 x 10CFU/mL for H. pylori) are inoculated directly onto freshly prepared antimicrobial containing Mueller-Hinton agar plates with 5% aged defibrinated sheep blood (>2-weeks old). The agar dilution plates are incubated at 35��C in a microaerobic environment produced by a gas generating system suitable for Campylobacter species. After 3 days of incubation, theMICs are recorded as the lowest concentration of antimicrobial agent required to inhibit growth of the organism. The clarithromycin and amoxicillin MIC values should be interpreted according to the following criteria: Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard clarithromycin and amoxicillin powders should provide the following MIC values:

Clarithromycin is contraindicated in patients with a known hypersensitivity to clarithromycin, erythromycin, or any of the macrolide antibiotics. Concomitant administration of clarithromycin and any of the following drugs is contraindicated: cisapride, pimozide, astemizole, terfenadine, and ergotamine or dihydroergotamine (see Drug Interactions). 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. For information about contraindications of other drugs indicated in combination with BIAXIN, refer to the CONTRAINDICATIONS section of their package inserts.

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dailymed-ingredient:D&C_Yellow_No._10, dailymed-ingredient:FD&C_Blue_No._1, dailymed-ingredient:croscarmellose_sodium, dailymed-ingredient:hydroxypropyl_cellulose, dailymed-ingredient:hypromellose, dailymed-ingredient:magnesium_stearate, dailymed-ingredient:microcrystalline_cellulose, dailymed-ingredient:povidone, dailymed-ingredient:pregelatinized_starch, dailymed-ingredient:propylene_glycol, dailymed-ingredient:silicon_dioxide, dailymed-ingredient:sorbic_acid, dailymed-ingredient:sorbitan_monooleate, dailymed-ingredient:stearic_acid, dailymed-ingredient:talc, dailymed-ingredient:titanium_dioxide, dailymed-ingredient:vanillin

CLARITHROMYCIN

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<0.01). Twenty percent of erythromycin-treated patients discontinued therapy due to adverse events compared to 4% of clarithromycin-treated patients. 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<0.001). One-third as many clarithromycin-treated patients reported diarrhea as did amoxicillin/potassium clavulanate-treated patients.<br/>Post-Marketing Experience: Allergic reactions ranging from urticaria and mild skin eruptions to rare cases of anaphylaxis, Stevens-Johnson syndrome and toxic epidermal necrolysis have occurred. Other spontaneously reported adverse events include glossitis, stomatitis, oral moniliasis, anorexia, vomiting, pancreatitis, tongue discoloration, thrombocytopenia, leukopenia, neutropenia, and dizziness. There have been reports of tooth discoloration in patients treated with BIAXIN. Tooth discoloration is usually reversible with professional dental cleaning. There have been isolated reports of hearing loss, which is usually reversible, occurring chiefly in elderly women. Reports of alterations of the sense of smell, usually in conjunction with taste perversion or taste loss have also been reported. Transient CNS events including anxiety, behavioral changes, confusional states, convulsions, depersonalization, disorientation, hallucinations, insomnia, depression, manic behavior, nightmares, psychosis, tinnitus, tremor, and vertigo have been reported during post-marketing surveillance. Events usually resolve with discontinuation of the drug. Hepatic dysfunction, including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been infrequently reported with clarithromycin. This hepatic dysfunction may be severe and is usually reversible. In very rare instances, hepatic failure with fatal outcome has been reported and generally has been associated with serious underlying diseases and/or concomitant medications. There have been rare reports of hypoglycemia, some of which have occurred in patients taking oral hypoglycemic agents or insulin. There have been post-marketing reports of BIAXIN XL tablets in the stool, many of which have occurred in patients with anatomic (including ileostomy or colostomy) or functional gastrointestinal disorders with shortened GI transit times. As with other macrolides, clarithromycin has been associated with QT prolongation and ventricular arrhythmias, including ventricular tachycardia and torsades de pointes. There have been reports of interstitial nephritis coincident with clarithromycin use. There have been post-marketing reports of colchicine toxicity with concomitant use of clarithromycin and colchicine, especially in the elderly, some of which occurred in patients with renal insufficiency. Deaths have been reported in some such patients. (See WARNINGS and PRECAUTIONS.)<br/>Changes in Laboratory Values: Changes in laboratory values with possible clinical significance were as follows:<br/>Hepatic: Elevated SGPT (ALT)<1%; SGOT (AST)<1%; GGT<1%; alkaline phosphatase<1%; LDH<1%; total bilirubin<1%<br/>Hematologic: Decreased WBC<1%; elevated prothrombin time 1%<br/>Renal: Elevated BUN 4%; elevated serum creatinine<1% GGT, alkaline phosphatase, and prothrombin time data are from adult studies only.

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:<br/>Adults (BIAXIN Filmtab Tablets and Granules for Oral Suspension): Pharyngitis/Tonsillitis due to Streptococcus pyogenes (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 S. pyogenes 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 Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae. Acute bacterial exacerbation of chronic bronchitis due to Haemophilus influenzae , Haemophilus parainfluenzae, Moraxella catarrhalis, or Streptococcus pneumoniae. Community-Acquired Pneumonia due to Haemophilus influenzae, Mycoplasma pneumoniae, Streptococcus pneumoniae, or Chlamydia pneumoniae (TWAR). Uncomplicated skin and skin structure infections due to Staphylococcus aureus , or Streptococcus pyogenes (Abscesses usually require surgical drainage). Disseminated mycobacterial infections due to Mycobacterium avium, or Mycobacterium intracellulare 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 H. pylori infection and duodenal ulcer disease (active or five-year history of duodenal ulcer) to eradicate H. pylori. 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 H. pylori 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 Microbiology section.) The eradication of H. pylori has been demonstrated to reduce the risk of duodenal ulcer recurrence.<br/>Children (BIAXIN Filmtab Tablets and Granules for Oral Suspension): Pharyngitis/Tonsillitis due to Streptococcus pyogenes. Community-Acquired Pneumonia due to Mycoplasma pneumoniae, Streptococcus pneumoniae, or Chlamydia pneumoniae (TWAR) Acute maxillary sinusitis due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae Acute otitis media due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae NOTE: For information on otitis media, see CLINICAL STUDIES - Otitis Media. Uncomplicated skin and skin structure infections due to Staphylococcus aureus, or Streptococcus pyogenes (Abscesses usually require surgical drainage.) Disseminated mycobacterial infections due to Mycobacterium avium, or Mycobacterium intracellulare<br/>Adults (BIAXIN XL Filmtab Tablets): 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 Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae Acute bacterial exacerbation of chronic bronchitis due to Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, or Streptococcus pneumoniae Community-Acquired Pneumonia due to Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Chlamydia pneumoniae (TWAR), or Mycoplasma pneumoniae THE EFFICACY AND SAFETY OF BIAXIN XL IN TREATING OTHER INFECTIONS FOR WHICH OTHER FORMULATIONS OF BIAXIN ARE APPROVED HAVE NOT BEEN ESTABLISHED.<br/>Prophylaxis: BIAXIN Filmtab tablets and BIAXIN Granules for oral suspension are indicated for the prevention of disseminated Mycobacterium avium 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.

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