CLARIGET Clarithromycin 125mg / 5mL Granule for Suspension 25mL
RXDRUG-DR-XY31313-25
Discreet Packaging
FDA-registered Products
FDA-licensed Pharmacies
Indications/Uses
Treatment of infections due to susceptible organisms.
Clariget/Clariget OD: Such infections include: Lower respiratory tract infections (eg, bronchitis, pneumonia); upper respiratory infections (eg, pharyngitis, sinusitis, tonsillitis); skin and soft tissue infections (eg, folliculitis, cellulitis, erysipelas)
Clariget: Acute otitis media in children. Leprosy; disseminated or localized mycobacterial infections due to Mycobacterium avium or M. intracellulare, localized infections due to M. chelonae, M. fortuitum or M. kansasii; used in some countries as an alternative to penicillins for prophylaxis of endocarditis; to eradicate Helicobacter pylori in treatment regimens for peptic ulcer disease. It has been tried in protozoal infections, including toxoplasmosis; prevention of disseminated M. avium complex (MAC) disease in patients with advanced HIV infection.
Clariget/Clariget OD: Such infections include: Lower respiratory tract infections (eg, bronchitis, pneumonia); upper respiratory infections (eg, pharyngitis, sinusitis, tonsillitis); skin and soft tissue infections (eg, folliculitis, cellulitis, erysipelas)
Clariget: Acute otitis media in children. Leprosy; disseminated or localized mycobacterial infections due to Mycobacterium avium or M. intracellulare, localized infections due to M. chelonae, M. fortuitum or M. kansasii; used in some countries as an alternative to penicillins for prophylaxis of endocarditis; to eradicate Helicobacter pylori in treatment regimens for peptic ulcer disease. It has been tried in protozoal infections, including toxoplasmosis; prevention of disseminated M. avium complex (MAC) disease in patients with advanced HIV infection.
Dosage/Direction for Use
Clariget: Adults: Usual Recommended Dose: One 250-mg tab twice daily. In more severe infections, the dosage can be increased to 500 mg twice daily. Usual Duration of Therapy: 6-14 days. The suspension may be used as an alternative dosage form for those adults that prefer a liquid medicine.
The following text is a suggested guide for determining dosage: Pharyngitis/Tonsillitis: 250 mg every 12 hrs for 10 days.
Acute Maxillary Sinusitis: 500 mg every 12 hrs for 14 days.
Acute Exacerbation of Chronic Bronchitis due to S. pneumoniae and M. catarrhalis: 250 mg every 12 hrs for 7-14 days; H. influenzae: 500 mg every 12 hrs for 7-14 days.
Pneumonia due to S. pneumoniae and M. pneumoniae: 250 mg every 12 hrs for 7-14 days.
Uncomplicated Skin and Skin Structure Infections: 250 mg every 12 hrs for 7-14 days.
Children: Usual Recommended Dose: 7.5 mg/kg twice daily up to a maximum of 500 mg twice daily. Usual Duration of Treatment: 5-10 days depending on the pathogen involved and the severity of the condition.
The following text is the suggested Pediatric Dosage Guideline for determining dosage based on body weight*:
8-11 kg (1-2 years)**: 62.5 mg or 2.5 mL (½ tsp); 12-19 kg (3-6 years): 125 mg or 5 mL (1 tsp); 20-29 kg (7-9 years): 187.5 mg or 7.5 mL (1½ tsp); 30-40 kg (10-12 years): 250 mg or 10 mL (2 tsp). All doses to be given twice daily.
*Children <8 kg should be dosed on a per kg basis (~7.5 mg/kg twice daily).
**Approximate ages.
Eradication of H. pylori Associated with Peptic Ulcer Disease: 500 mg twice daily given with another antibacterial and either a proton pump inhibitor or a histamine H2-receptor antagonist for 7-14 days.
Mycobacterial Infections: Recommended Dose: 7.5-15 mg/kg twice daily in children with disseminated or localized mycobacterial infections (M. avium, M. intracellulare, M. chelonae, M. fortuitum and M. kansasii).
Treatment of disseminated MAC infections in AIDS patients should be continued as long as clinical and microbiological benefit is demonstrated. Treatment of other mycobacterial infections should continue at the discretion of the physician. Clarithromycin should be used in conjunction with other antimycobacterial agents. Dosing recommendations for children are in the table. (See table.)
The following text is a suggested guide for determining dosage: Pharyngitis/Tonsillitis: 250 mg every 12 hrs for 10 days.
Acute Maxillary Sinusitis: 500 mg every 12 hrs for 14 days.
Acute Exacerbation of Chronic Bronchitis due to S. pneumoniae and M. catarrhalis: 250 mg every 12 hrs for 7-14 days; H. influenzae: 500 mg every 12 hrs for 7-14 days.
Pneumonia due to S. pneumoniae and M. pneumoniae: 250 mg every 12 hrs for 7-14 days.
Uncomplicated Skin and Skin Structure Infections: 250 mg every 12 hrs for 7-14 days.
Children: Usual Recommended Dose: 7.5 mg/kg twice daily up to a maximum of 500 mg twice daily. Usual Duration of Treatment: 5-10 days depending on the pathogen involved and the severity of the condition.
The following text is the suggested Pediatric Dosage Guideline for determining dosage based on body weight*:
8-11 kg (1-2 years)**: 62.5 mg or 2.5 mL (½ tsp); 12-19 kg (3-6 years): 125 mg or 5 mL (1 tsp); 20-29 kg (7-9 years): 187.5 mg or 7.5 mL (1½ tsp); 30-40 kg (10-12 years): 250 mg or 10 mL (2 tsp). All doses to be given twice daily.
*Children <8 kg should be dosed on a per kg basis (~7.5 mg/kg twice daily).
**Approximate ages.
Eradication of H. pylori Associated with Peptic Ulcer Disease: 500 mg twice daily given with another antibacterial and either a proton pump inhibitor or a histamine H2-receptor antagonist for 7-14 days.
Mycobacterial Infections: Recommended Dose: 7.5-15 mg/kg twice daily in children with disseminated or localized mycobacterial infections (M. avium, M. intracellulare, M. chelonae, M. fortuitum and M. kansasii).
Treatment of disseminated MAC infections in AIDS patients should be continued as long as clinical and microbiological benefit is demonstrated. Treatment of other mycobacterial infections should continue at the discretion of the physician. Clarithromycin should be used in conjunction with other antimycobacterial agents. Dosing recommendations for children are in the table. (See table.)
Renal Impairment: Clariget 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 (CrCl <30 mL/min), with or without coexisting hepatic impairment, the dose should be halved or the dosing interval doubled.
In children with creatinine clearance <30 mL/min, the dosage of clarithromycin should be reduced by ½ ie, up to 250 mg once daily or 250 mg twice daily in more severe infections. Dosage should not be continued beyond 14 days in these patients.
Susp: Directions for Preparation: Fill previously boiled and cooled water up to the line mark on the bottle and shake vigorously. The reconstituted suspension can be used for up to 14 days when stored at the required conditions.
Clariget OD: Usual Recommended Dose: Adult: 500 mg once daily.
More severe infections: Dosage may be increased to 1000 mg once daily (2 x 500 mg).
Usual Duration of Therapy: 5-14 days, excluding treatment of community-acquired pneumonia and sinusitis which require 6-14 days of therapy.
Renal Impairment: Moderate Renal Function (CrCl 30-60 mL/min): 50% dosage reduction should be implemented resulting in a maximum dose of Clariget OD 1 tablet/day.
Administration: Clariget OD should be taken with food and should be swallowed whole and not chewed, broken or crushed.
In children with creatinine clearance <30 mL/min, the dosage of clarithromycin should be reduced by ½ ie, up to 250 mg once daily or 250 mg twice daily in more severe infections. Dosage should not be continued beyond 14 days in these patients.
Susp: Directions for Preparation: Fill previously boiled and cooled water up to the line mark on the bottle and shake vigorously. The reconstituted suspension can be used for up to 14 days when stored at the required conditions.
Clariget OD: Usual Recommended Dose: Adult: 500 mg once daily.
More severe infections: Dosage may be increased to 1000 mg once daily (2 x 500 mg).
Usual Duration of Therapy: 5-14 days, excluding treatment of community-acquired pneumonia and sinusitis which require 6-14 days of therapy.
Renal Impairment: Moderate Renal Function (CrCl 30-60 mL/min): 50% dosage reduction should be implemented resulting in a maximum dose of Clariget OD 1 tablet/day.
Administration: Clariget OD should be taken with food and should be swallowed whole and not chewed, broken or crushed.
Overdosage
Overdosage of clarithromycin can cause GI symptoms eg, 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.
Administration
May be taken with or without food.
Contraindications
Patients with known hypersensitivity to macrolide antibiotic drugs.
Clariget: Concomitant administration of clarithromycin with any of the following medicines is contraindicated: Astemizole, cisapride, pimozide and terfenadine.
Clariget OD: Patients with creatinine clearance <30 mL/min.
Concomitant administration with the following drugs: Astemizole, pimozide, cisapride, terfenadine, ergotamine or dihydroergotamine.
Clarithromycin in combination with ranitidine bismuth citrate should not be used in patients with a history of acute porphyria.
Clariget: Concomitant administration of clarithromycin with any of the following medicines is contraindicated: Astemizole, cisapride, pimozide and terfenadine.
Clariget OD: Patients with creatinine clearance <30 mL/min.
Concomitant administration with the following drugs: Astemizole, pimozide, cisapride, terfenadine, ergotamine or dihydroergotamine.
Clarithromycin in combination with ranitidine bismuth citrate should not be used in patients with a history of acute porphyria.
Special Precautions
Clariget: Caution is required in patients with impaired renal or hepatic function and doses should be reduced in those with severe renal impairment.
Caution should also be paid to the possibility of cross-resistance between clarithromycin and other macrolide drugs, as well as lincomycin and clindamycin.
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including macrolides, and may range in severity from mild to life-threatening.
Clarithromycin in combination with ranitidine bismuth citrate therapy should not be used in patients with a history of acute porphyria.
Clariget OD: Long-term use may, as with other antibiotics, result in colonization with increased numbers of non-susceptible bacteria and fungi. If superinfections occur, appropriate therapy should be instituted.
Caution should be exercised in administering clarithromycin to patients with impaired hepatic function and moderate renal function.
Caution should also be paid to the possibility of cross-resistances between clarithromycin and other macrolide drugs, as well as lincomycin and clindamycin.
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including clarithromycin, and may range in severity from mild to life-threatening. Therefore it is important to consider this diagnosis in patients who have diarrhea subsequent to the administration of antibacterial agents. After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated.
It may cause exacerbation of symptoms of myasthenia gravis.
Hepatic Impairment and Renal Insufficiency: 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.
Use in Children: Clariget OD: Safety and effectiveness of clarithromycin in pediatric patients <6 months have not been established.
Use in Elderly: Clariget OD: Elderly patients with severe renal impairment may require a decrease in dose.
Use in Pregnancy & Lactation: Clariget: Clarithromycin is excreted into human breast milk, therefore, clarithromycin should not be used during pregnancy and breastfeeding unless the potential benefit justifies a potential risk to the fetus.
If clarithromycin pediatric suspension is considered for patients of postpubertal age, the physician should carefully weigh the benefits against the risk when pregnancy is either suspected or confirmed.
Clariget OD: Clarithromycin should be used during pregnancy only if the potential benefits justifies the potential risk to the fetus. It should not be prescribed particularly during the first 3 months of pregnancy.
The safety of clarithromycin during breastfeeding of infants has not been established. Clarithromycin is excreted into human breast milk.
Caution should also be paid to the possibility of cross-resistance between clarithromycin and other macrolide drugs, as well as lincomycin and clindamycin.
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including macrolides, and may range in severity from mild to life-threatening.
Clarithromycin in combination with ranitidine bismuth citrate therapy should not be used in patients with a history of acute porphyria.
Clariget OD: Long-term use may, as with other antibiotics, result in colonization with increased numbers of non-susceptible bacteria and fungi. If superinfections occur, appropriate therapy should be instituted.
Caution should be exercised in administering clarithromycin to patients with impaired hepatic function and moderate renal function.
Caution should also be paid to the possibility of cross-resistances between clarithromycin and other macrolide drugs, as well as lincomycin and clindamycin.
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including clarithromycin, and may range in severity from mild to life-threatening. Therefore it is important to consider this diagnosis in patients who have diarrhea subsequent to the administration of antibacterial agents. After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated.
It may cause exacerbation of symptoms of myasthenia gravis.
Hepatic Impairment and Renal Insufficiency: 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.
Use in Children: Clariget OD: Safety and effectiveness of clarithromycin in pediatric patients <6 months have not been established.
Use in Elderly: Clariget OD: Elderly patients with severe renal impairment may require a decrease in dose.
Use in Pregnancy & Lactation: Clariget: Clarithromycin is excreted into human breast milk, therefore, clarithromycin should not be used during pregnancy and breastfeeding unless the potential benefit justifies a potential risk to the fetus.
If clarithromycin pediatric suspension is considered for patients of postpubertal age, the physician should carefully weigh the benefits against the risk when pregnancy is either suspected or confirmed.
Clariget OD: Clarithromycin should be used during pregnancy only if the potential benefits justifies the potential risk to the fetus. It should not be prescribed particularly during the first 3 months of pregnancy.
The safety of clarithromycin during breastfeeding of infants has not been established. Clarithromycin is excreted into human breast milk.
Use In Pregnancy & Lactation
Clariget: Clarithromycin is excreted into human breast milk, therefore, clarithromycin should not be used during pregnancy and breastfeeding unless the potential benefit justifies a potential risk to the fetus.
If clarithromycin pediatric suspension is considered for patients of postpubertal age, the physician should carefully weigh the benefits against the risk when pregnancy is either suspected or confirmed.
Clariget OD: Clarithromycin should be used during pregnancy only if the potential benefits justifies the potential risk to the fetus. It should not be prescribed particularly during the first 3 months of pregnancy.
The safety of clarithromycin during breastfeeding of infants has not been established. Clarithromycin is excreted into human breast milk.
If clarithromycin pediatric suspension is considered for patients of postpubertal age, the physician should carefully weigh the benefits against the risk when pregnancy is either suspected or confirmed.
Clariget OD: Clarithromycin should be used during pregnancy only if the potential benefits justifies the potential risk to the fetus. It should not be prescribed particularly during the first 3 months of pregnancy.
The safety of clarithromycin during breastfeeding of infants has not been established. Clarithromycin is excreted into human breast milk.
Adverse Reactions
Clariget/Clariget OD: Clarithromycin is generally well tolerated.
The most frequently reported side effects of clarithromycin in clinical studies were GI-related ie, nausea, dyspepsia, abdominal pain, vomiting and diarrhea. Other reported side effects include headache, taste perversion and transient elevations of liver enzymes.
Headache and rashes from mild skin eruptions to rarely, Stevens-Johnson syndrome have occurred. There have also been reports of transient CNS effects eg, anxiety, dizziness, insomnia, hallucinations and confusion.
Other adverse effects include hypoglycemia and thrombocytopenia. Interstitial nephritis, renal failure, hearing loss, glossitis, stomatitis, oral monilia and tongue discoloration have been reported with clarithromycin therapy.
Adverse Laboratory Changes: Abnormal liver function test results may occur following therapy with clarithromycin. Changes in laboratory parameters without regard to drug relationship are: Hepatic: Elevated SGPT (ALT), SGOT (AST), GGT, alkaline phosphates, LDH, bilirubin.
Hematologic: Decreased WBC, prothrombin time.
Renal: Elevated BUN, serum creatinine.
Clariget: The safety profile of the pediatric formulation is similar to that of the 250-mg tablet in adult patients.
Hematologic: Decreased platelet count. Elevated prothrombin.
Immunocompromised Pediatric Patients: In AIDS and other immunocompromised patients treated with the higher doses of clarithromycin over long periods of time for mycobacterial infections, it is often difficult to distinguish adverse events possibly associated with clarithromycin administration from underlying signs of HIV disease or intercurrent illness.
The most frequently reported adverse events, excluding those due to the patient's concurrent condition, were tinnitus, deafness, vomiting, nausea, abdominal pain, purpuric rash, pancreatitis and increased amylase. Evaluations of laboratory values for these patients were made by analyzing those values outside the seriously abnormal level (ie, the extremely high or low limit) for the specified test. None of these seriously abnormal values for these laboratory parameters were reported for patients receiving the highest dosage (25 mg/kg/day) of clarithromycin.
The most frequently reported side effects of clarithromycin in clinical studies were GI-related ie, nausea, dyspepsia, abdominal pain, vomiting and diarrhea. Other reported side effects include headache, taste perversion and transient elevations of liver enzymes.
Headache and rashes from mild skin eruptions to rarely, Stevens-Johnson syndrome have occurred. There have also been reports of transient CNS effects eg, anxiety, dizziness, insomnia, hallucinations and confusion.
Other adverse effects include hypoglycemia and thrombocytopenia. Interstitial nephritis, renal failure, hearing loss, glossitis, stomatitis, oral monilia and tongue discoloration have been reported with clarithromycin therapy.
Adverse Laboratory Changes: Abnormal liver function test results may occur following therapy with clarithromycin. Changes in laboratory parameters without regard to drug relationship are: Hepatic: Elevated SGPT (ALT), SGOT (AST), GGT, alkaline phosphates, LDH, bilirubin.
Hematologic: Decreased WBC, prothrombin time.
Renal: Elevated BUN, serum creatinine.
Clariget: The safety profile of the pediatric formulation is similar to that of the 250-mg tablet in adult patients.
Hematologic: Decreased platelet count. Elevated prothrombin.
Immunocompromised Pediatric Patients: In AIDS and other immunocompromised patients treated with the higher doses of clarithromycin over long periods of time for mycobacterial infections, it is often difficult to distinguish adverse events possibly associated with clarithromycin administration from underlying signs of HIV disease or intercurrent illness.
The most frequently reported adverse events, excluding those due to the patient's concurrent condition, were tinnitus, deafness, vomiting, nausea, abdominal pain, purpuric rash, pancreatitis and increased amylase. Evaluations of laboratory values for these patients were made by analyzing those values outside the seriously abnormal level (ie, the extremely high or low limit) for the specified test. None of these seriously abnormal values for these laboratory parameters were reported for patients receiving the highest dosage (25 mg/kg/day) of clarithromycin.
Drug Interactions
Clariget: Data available to date indicate that clarithromycin is metabolized primarily by the hepatic cytochrome P-450 3A (CYP3A) isozyme. This is an important mechanism determining many drug interactions.
The metabolism of other drugs by this system may be inhibited by concomitant administration with clarithromycin and may be associated with elevations in serum levels of drug classes known or suspected to be metabolized by the same CYP450 and CYP3A isozyme.
Other Drug Interactions: Elevated digoxin serum concentrations have been reported in patients receiving clarithromycin tablets and digoxin concomitantly. Monitoring of serum digoxin levels should be considered.
There have been post-marketing reports of Torsades de pointes occurring with concurrent use of clarithromycin and quinidine or disopyramide. Serum levels of these medications should be monitored during clarithromycin therapy.
Rhabdomyolysis coincident with the co-administration of clarithromycin and the HMG-CoA reductase inhibitors eg, lovastatin and simvastatin has rarely been reported.
Antiretroviral Drug Interactions: Simultaneous oral administration of clarithromycin tablets and zidovudine to HIV-infected adult patients may result in decreased steady-state zidovudine concentrations. Because clarithromycin appears to interfere with the absorption of simultaneously administered oral zidovudine, this interaction can be largely avoided by staggering the doses of clarithromycin and zidovudine. This interaction does not appear to occur in pediatric HIV-infected patients taking clarithromycin suspension with zidovudine or dideoxyinosine.
A pharmacokinetic study demonstrated that the concomitant administration of ritonavir 200 mg every 8 hrs and clarithromycin 500 mg every 12 hrs resulted in a marked inhibition of the metabolism of clarithromycin.
For patients with renal impairment, the following dosage adjustments should be considered: For patients with CrCl 30-60 mL/min, the dose of clarithromycin should be reduced by 50%. For patients with CrCl <30 mL, the dose of clarithromycin should be decreased by 75%. Doses of clarithromycin >1 g/day should not be co-administered with ritonavir.
Clariget OD: As with other macrolide antibiotics, the use of clarithromycin in patients concurrently taking drugs metabolized by the cytochrome P-450 system (eg, cilostazol, methylprednisolone, anticoagulants eg, warfarin, quinidine, sildenafil, ergot alkaloids, alprazolam, triazolam, midazolam, disopyramide, lovastatin, rifabutin, phenytoin, cyclosporin, vinblastine, valproate and tacrolimus) may be associated with elevations in serum levels of these other drugs.
Digoxin: Elevated digoxin serum concentrations have been reported in patients receiving clarithromycin tablets and digoxin concomitantly. Monitoring of serum digoxin levels should be considered.
Quinidine/Disopyramide: There have been post-marketed reports of Torsades de pointes occurring with concurrent use of clarithromycin and quinidine or disopyramide. Electrocardiogram and serum levels of these medications should be monitored during clarithromycin therapy.
HMG-CoA Reductase Inhibitors: As with other macrolides, clarithromycin has been reported to increase concentrations of HMG-CoA reductase inhibitors (eg, statins). Rhabdomyolysis has also been reported in patients taking these drugs concomitantly.
Theophylline, Carbamazepine: The administration of clarithromycin to patients receiving theophylline or carbamazepine has been associated with an increase in serum theophylline or carbamazepine levels.
Oral Anticoagulants: Concomitant administration of clarithromycin and oral anticoagulants may potentiate the effects of oral anticoagulants. Prothrombin time should be carefully monitored while patients are receiving clarithromycin and oral anticoagulants simultaneously.
Ritonavir: Ritonavir increases AUC, Cmax and Cmin of clarithromycin when administered concurrently. Because of the large therapeutic window for clarithromycin, no dosage reduction should be necessary in patients with normal renal function. However, for patients with renal impairment, the following dosage adjustments should be considered: For patients with CrCl 30-60 mL/min, the dose of clarithromycin should be reduced by 50%. For patients with CrCl <30 mL/min, the dose of clarithromycin should be decreased by 75%. Doses of clarithromycin >1 g/day should not be co-administered with ritonavir.
Efavirenz, Nevirapine, Rifampicin and Rifabutin: Strong inducers of the cytochrome P-450 metabolism system eg, efavirenz, nevirapine, rifampicin and rifabutin may accelerate the metabolism of clarithromycin and thus, lower the plasma levels of clarithromycin. Since the microbiological activities of clarithromycin and 14-OH-clarithromycin are different for different bacteria, the intended therapeutic effect could be impaired during concomitant administration of clarithromycin and enzyme inducers.
Sildenafil, Tadalafil and Vardenafil: Each of these phosphodiesterase inhibitors is metabolized, at least in part, by CYP3A, and CYP3A may be inhibited by concomitantly administered clarithromycin. Reduction in sildenafil, tadalafil and vardenafil dosages should be considered when these drugs are co-administered with clarithromycin.
Triazolam: Drug interactions and CNS effects (eg, somnolence and confusion) with the concomitant use of clarithromycin and triazolam have been reported. Monitoring the patient for increased CNS pharmacological effects is suggested.
Colchicine: When clarithromycin and colchicine are administered together, inhibition of Pgp and/or CYP3A by clarithromycin may lead to increased exposure to colchicine. Patients should be monitored for clinical symptoms of colchicine toxicity.
Itraconazole: Both clarithromycin and itraconazole are substrates and inhibitors of CYP3A. Clarithromycin may increase the plasma levels of itraconazole, while itraconazole may increase the plasma levels of clarithromycin. Patients taking itraconazole and clarithromycin concomitantly should be monitored closely for signs and symptoms of increased or prolonged pharmacological effect.
Zidovudine: Simultaneous oral administration of clarithromycin tablets and zidovudine to HIV-infected adult patients may result in decreased steady-state zidovudine concentrations. This interaction does not appear to occur in pediatric HIV-infected patients taking clarithromycin suspension with zidovudine or dideoxyinosine.
The metabolism of other drugs by this system may be inhibited by concomitant administration with clarithromycin and may be associated with elevations in serum levels of drug classes known or suspected to be metabolized by the same CYP450 and CYP3A isozyme.
Other Drug Interactions: Elevated digoxin serum concentrations have been reported in patients receiving clarithromycin tablets and digoxin concomitantly. Monitoring of serum digoxin levels should be considered.
There have been post-marketing reports of Torsades de pointes occurring with concurrent use of clarithromycin and quinidine or disopyramide. Serum levels of these medications should be monitored during clarithromycin therapy.
Rhabdomyolysis coincident with the co-administration of clarithromycin and the HMG-CoA reductase inhibitors eg, lovastatin and simvastatin has rarely been reported.
Antiretroviral Drug Interactions: Simultaneous oral administration of clarithromycin tablets and zidovudine to HIV-infected adult patients may result in decreased steady-state zidovudine concentrations. Because clarithromycin appears to interfere with the absorption of simultaneously administered oral zidovudine, this interaction can be largely avoided by staggering the doses of clarithromycin and zidovudine. This interaction does not appear to occur in pediatric HIV-infected patients taking clarithromycin suspension with zidovudine or dideoxyinosine.
A pharmacokinetic study demonstrated that the concomitant administration of ritonavir 200 mg every 8 hrs and clarithromycin 500 mg every 12 hrs resulted in a marked inhibition of the metabolism of clarithromycin.
For patients with renal impairment, the following dosage adjustments should be considered: For patients with CrCl 30-60 mL/min, the dose of clarithromycin should be reduced by 50%. For patients with CrCl <30 mL, the dose of clarithromycin should be decreased by 75%. Doses of clarithromycin >1 g/day should not be co-administered with ritonavir.
Clariget OD: As with other macrolide antibiotics, the use of clarithromycin in patients concurrently taking drugs metabolized by the cytochrome P-450 system (eg, cilostazol, methylprednisolone, anticoagulants eg, warfarin, quinidine, sildenafil, ergot alkaloids, alprazolam, triazolam, midazolam, disopyramide, lovastatin, rifabutin, phenytoin, cyclosporin, vinblastine, valproate and tacrolimus) may be associated with elevations in serum levels of these other drugs.
Digoxin: Elevated digoxin serum concentrations have been reported in patients receiving clarithromycin tablets and digoxin concomitantly. Monitoring of serum digoxin levels should be considered.
Quinidine/Disopyramide: There have been post-marketed reports of Torsades de pointes occurring with concurrent use of clarithromycin and quinidine or disopyramide. Electrocardiogram and serum levels of these medications should be monitored during clarithromycin therapy.
HMG-CoA Reductase Inhibitors: As with other macrolides, clarithromycin has been reported to increase concentrations of HMG-CoA reductase inhibitors (eg, statins). Rhabdomyolysis has also been reported in patients taking these drugs concomitantly.
Theophylline, Carbamazepine: The administration of clarithromycin to patients receiving theophylline or carbamazepine has been associated with an increase in serum theophylline or carbamazepine levels.
Oral Anticoagulants: Concomitant administration of clarithromycin and oral anticoagulants may potentiate the effects of oral anticoagulants. Prothrombin time should be carefully monitored while patients are receiving clarithromycin and oral anticoagulants simultaneously.
Ritonavir: Ritonavir increases AUC, Cmax and Cmin of clarithromycin when administered concurrently. Because of the large therapeutic window for clarithromycin, no dosage reduction should be necessary in patients with normal renal function. However, for patients with renal impairment, the following dosage adjustments should be considered: For patients with CrCl 30-60 mL/min, the dose of clarithromycin should be reduced by 50%. For patients with CrCl <30 mL/min, the dose of clarithromycin should be decreased by 75%. Doses of clarithromycin >1 g/day should not be co-administered with ritonavir.
Efavirenz, Nevirapine, Rifampicin and Rifabutin: Strong inducers of the cytochrome P-450 metabolism system eg, efavirenz, nevirapine, rifampicin and rifabutin may accelerate the metabolism of clarithromycin and thus, lower the plasma levels of clarithromycin. Since the microbiological activities of clarithromycin and 14-OH-clarithromycin are different for different bacteria, the intended therapeutic effect could be impaired during concomitant administration of clarithromycin and enzyme inducers.
Sildenafil, Tadalafil and Vardenafil: Each of these phosphodiesterase inhibitors is metabolized, at least in part, by CYP3A, and CYP3A may be inhibited by concomitantly administered clarithromycin. Reduction in sildenafil, tadalafil and vardenafil dosages should be considered when these drugs are co-administered with clarithromycin.
Triazolam: Drug interactions and CNS effects (eg, somnolence and confusion) with the concomitant use of clarithromycin and triazolam have been reported. Monitoring the patient for increased CNS pharmacological effects is suggested.
Colchicine: When clarithromycin and colchicine are administered together, inhibition of Pgp and/or CYP3A by clarithromycin may lead to increased exposure to colchicine. Patients should be monitored for clinical symptoms of colchicine toxicity.
Itraconazole: Both clarithromycin and itraconazole are substrates and inhibitors of CYP3A. Clarithromycin may increase the plasma levels of itraconazole, while itraconazole may increase the plasma levels of clarithromycin. Patients taking itraconazole and clarithromycin concomitantly should be monitored closely for signs and symptoms of increased or prolonged pharmacological effect.
Zidovudine: Simultaneous oral administration of clarithromycin tablets and zidovudine to HIV-infected adult patients may result in decreased steady-state zidovudine concentrations. This interaction does not appear to occur in pediatric HIV-infected patients taking clarithromycin suspension with zidovudine or dideoxyinosine.
Storage
Store at temperatures not exceeding 30°C. Protect from sunlight and exposure.
Action
Antibacterial.
Pharmacology: Pharmacodynamics: Mechanism of Action: Clariget OD: Clarithromycin binds to the 50S ribosomal subunit of susceptible microorganisms and inhibits the translocation step resulting in inhibition of protein synthesis. The minimum inhibitory concentrations (MICs) of clarithromycin are generally 2-fold lower than the MICs of erythromycin. The 14-hydroxy metabolite of clarithromycin also has antimicrobial activity. 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.
Pharmacokinetics: Absorption: Clariget: Clarithromycin is rapidly absorbed from the GI tract after oral administration and the bioavailability of the parent drug is about 55%. Food slightly delays the absorption of clarithromycin but does not affect the extent of bioavailability, therefore it may be given without regard to food. Peak concentrations of clarithromycin and its principal active metabolite 14-hydroxyclarithromycin are reported to be about 0.6 and 0.7 mcg/mL, respectively, following a single 250-mg dose by mouth; at steady-state, the same dose given every 12 hrs as tablets produces peak concentrations of clarithromycin of about 1 mcg/mL. The same dose given as a suspension produces a steady-state plasma concentration of about 2 mcg/mL. The time to peak concentration is about 2-3 hrs.
The pharmacokinetics of clarithromycin is nonlinear and dose dependent; high doses may produce disproportionate increases in peak concentration of the parent drug, due to saturation of the metabolic pathways.
Clariget OD: Clarithromycin extended-release tablets provide extended absorption of clarithromycin from the gastrointestinal tract after oral administration. The absolute bioavailability is approximately 50%. Steady-state peak plasma concentrations of approximately 1-2 mcg/mL were achieved about 5-6 hrs after oral administration of a single clarithromycin 500 mg extended-release tablet once daily. For 14-OH clarithromycin, steady-state peak plasma concentrations of approximately 0.6 mcg/mL were attained about 6 hrs after dosing. Little or no unpredicted accumulation was found and the metabolic disposition did not change following multiple dosing.
Effect of Food: Clariget OD: The extent of formation of 14-OH clarithromycin following administration of clarithromycin extended-release 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, clarithromycin extended-release tablets should be taken with food.
Distribution: Clarithromycin and its principal metabolite are widely distributed and tissue concentrations exceed those in serum, in part because of intracellular uptake.
Clariget: Volume of distribution is 243-266 L.
Clariget OD: The protein binding of clarithromycin in human plasma averaged about 70%.
Metabolism and Excretion: Clariget: It is extensively metabolized in the liver and excreted in feces via the bile. Substantial amounts are excreted in urine; at steady-state, about 20 and 30% of a 250- or 500-mg dose, respectively, is excreted in this way as unchanged drug. 14-Hydroxyclarithromycin as well as other metabolites are also excreted in the urine accounting for 10-15% of the dose. The terminal t½ of clarithromycin is reportedly about 3-4 hrs in patients receiving 250-mg doses twice daily and about 5-7 hrs in those receiving 500 mg twice daily.
The principal metabolite, 14-OH-clarithromycin, has an elimination t½ of 5-6 hrs after a dose of 250 mg every 12 hrs. With a dose of 500 mg every 12 hrs, its elimination t½ is about 7 hrs. With either dose, the steady-state concentration of this metabolite is generally attained within 2-3 days.
Clariget OD: It is extensively metabolized in the liver and undergoes first-pass metabolism. Elimination half-lives of the parent drug and metabolite were approximately 5.3 hrs and 7.7 hrs, respectively. Urinary excretion accounts for approximately 40% of the clarithromycin dose. Fecal elimination accounts for approximately 30%. The apparent half-lives of both clarithromycin and its hydroxylated metabolite tended to be longer at higher doses.
Special Populations: Clariget: Hepatic Impairment: The steady-state concentrations of clarithromycin in patients with impaired hepatic function did not differ from those of 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.
Renal Impairment: The pharmacokinetics of clarithromycin was also altered in subjects with impaired renal function who received multiple 500-mg oral doses. The plasma levels, t½, Cmax and Cmin for both clarithromycin and its 14-OH metabolite were higher and the AUC was larger in subjects with renal impairment than its normal subjects. The extent to which these parameters differed was correlated with the degree of renal impairment; the more severe the renal impairment, the more significant the difference.
Elderly Subjects: In a comparative study of healthy, young adults and healthy, elderly subjects given multiple 500-mg oral doses of clarithromycin, the circulating plasma levels were higher and elimination was slower in the elderly group compared to the younger group. However, there was no difference between the 2 groups when renal clearance of clarithromycin was correlated with creatinine clearance. It was concluded from these results that any effect on the handling of clarithromycin is related to renal function and not subject to age.
Patients with Mycobacterial Infections: Steady-state concentrations of clarithromycin and 14-OH-clarithromycin observed following administration of usual doses to patients with HIV infections were similar to those observed in normal subjects. However, at the higher doses which may be required to treat mycobacterial infections, clarithromycin concentrations can be much higher than those observed at usual doses. In children with HIV infection taking clarithromycin 15-30 mg/kg/day in 2 divided doses, steady-state Cmax values generally ranged from 8-20 mcg/mL. However, Cmax values as high as 23 mcg/mL have been observed in HIV-infected pediatric patients taking 30 mg/kg/day in 2 divided doses as clarithromycin pediatric suspension. Elimination half-lives appeared to be lengthened at these higher doses as compared to that observed with usual doses in normal subjects. The higher plasma concentrations and longer elimination half-lives observed at these doses are consistent with the known nonlinearity in clarithromycin pharmacokinetics.
Microbiology: Clariget: Clarithromycin exerts its antibacterial action by binding to the 50S ribosomal subunits of susceptible bacteria and suppresses protein synthesis.
Clarithromycin has demonstrated excellent in vitro activity against both standard strains of bacteria and clinical isolates. It is highly potent against a wide variety of aerobic and anaerobic gram-positive and gram-negative organisms. The minimum inhibitory concentrations (MICs) of clarithromycin are generally 1 log2 dilution more potent than the MICs of erythromycin.
Clarithromycin is reported to be more active than erythromycin against susceptible streptococci and staphylococci in vitro as well as against some other species including Moraxella catarrhalis (Branhamella catarrhalis), Legionella spp, Chlamydia trachomatis and Ureaplasma urealyticum. Clarithromycin is reported to be more active than erythromycin or azithromycin against some mycobacteria including Mycobacterium avium complex and against M. leprae. It is reported to have some in vitro activity against the protozoan Toxoplasma gondii and may have some activity against cryptosporidia. The major metabolite 14-hydroxyclarithromycin is also active, and may enhance the activity of clarithromycin in vivo, notably against Haemophilus influenzae.
In vitro data also indicates that clarithromycin has excellent activity against Legionella pneumophila and Mycoplasma pneumoniae. It is bactericidal to Helicobacter pylori; this activity of clarithromycin is greater at neutral pH than at acid pH. In vitro and in vivo data show that this antibiotic has activity against clinically significant mycobacterial species.
Clariget OD: Clarithromycin has shown to be active against the following microorganisms: Aerobic Gram-positive Microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Listeria monocytogenes.
Aerobic Gram-negative Microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Legionella spp (eg, Legionella pneumophila).
Anaerobes: Clostridium perfringens, Peptococcus sp, Peptostreptococcus sp, Propionibacterium acnes.
Mycobacteria: Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum, MAC (consisting of Mycobacterium avium, Mycobacterium intracellulare).
Other Microorganisms: Mycoplasma pneumoniae, Chlamydia pneumonia (TWAR), Chlamydia trachomatis, Ureaplasma urealyticum.
Pharmacology: Pharmacodynamics: Mechanism of Action: Clariget OD: Clarithromycin binds to the 50S ribosomal subunit of susceptible microorganisms and inhibits the translocation step resulting in inhibition of protein synthesis. The minimum inhibitory concentrations (MICs) of clarithromycin are generally 2-fold lower than the MICs of erythromycin. The 14-hydroxy metabolite of clarithromycin also has antimicrobial activity. 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.
Pharmacokinetics: Absorption: Clariget: Clarithromycin is rapidly absorbed from the GI tract after oral administration and the bioavailability of the parent drug is about 55%. Food slightly delays the absorption of clarithromycin but does not affect the extent of bioavailability, therefore it may be given without regard to food. Peak concentrations of clarithromycin and its principal active metabolite 14-hydroxyclarithromycin are reported to be about 0.6 and 0.7 mcg/mL, respectively, following a single 250-mg dose by mouth; at steady-state, the same dose given every 12 hrs as tablets produces peak concentrations of clarithromycin of about 1 mcg/mL. The same dose given as a suspension produces a steady-state plasma concentration of about 2 mcg/mL. The time to peak concentration is about 2-3 hrs.
The pharmacokinetics of clarithromycin is nonlinear and dose dependent; high doses may produce disproportionate increases in peak concentration of the parent drug, due to saturation of the metabolic pathways.
Clariget OD: Clarithromycin extended-release tablets provide extended absorption of clarithromycin from the gastrointestinal tract after oral administration. The absolute bioavailability is approximately 50%. Steady-state peak plasma concentrations of approximately 1-2 mcg/mL were achieved about 5-6 hrs after oral administration of a single clarithromycin 500 mg extended-release tablet once daily. For 14-OH clarithromycin, steady-state peak plasma concentrations of approximately 0.6 mcg/mL were attained about 6 hrs after dosing. Little or no unpredicted accumulation was found and the metabolic disposition did not change following multiple dosing.
Effect of Food: Clariget OD: The extent of formation of 14-OH clarithromycin following administration of clarithromycin extended-release 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, clarithromycin extended-release tablets should be taken with food.
Distribution: Clarithromycin and its principal metabolite are widely distributed and tissue concentrations exceed those in serum, in part because of intracellular uptake.
Clariget: Volume of distribution is 243-266 L.
Clariget OD: The protein binding of clarithromycin in human plasma averaged about 70%.
Metabolism and Excretion: Clariget: It is extensively metabolized in the liver and excreted in feces via the bile. Substantial amounts are excreted in urine; at steady-state, about 20 and 30% of a 250- or 500-mg dose, respectively, is excreted in this way as unchanged drug. 14-Hydroxyclarithromycin as well as other metabolites are also excreted in the urine accounting for 10-15% of the dose. The terminal t½ of clarithromycin is reportedly about 3-4 hrs in patients receiving 250-mg doses twice daily and about 5-7 hrs in those receiving 500 mg twice daily.
The principal metabolite, 14-OH-clarithromycin, has an elimination t½ of 5-6 hrs after a dose of 250 mg every 12 hrs. With a dose of 500 mg every 12 hrs, its elimination t½ is about 7 hrs. With either dose, the steady-state concentration of this metabolite is generally attained within 2-3 days.
Clariget OD: It is extensively metabolized in the liver and undergoes first-pass metabolism. Elimination half-lives of the parent drug and metabolite were approximately 5.3 hrs and 7.7 hrs, respectively. Urinary excretion accounts for approximately 40% of the clarithromycin dose. Fecal elimination accounts for approximately 30%. The apparent half-lives of both clarithromycin and its hydroxylated metabolite tended to be longer at higher doses.
Special Populations: Clariget: Hepatic Impairment: The steady-state concentrations of clarithromycin in patients with impaired hepatic function did not differ from those of 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.
Renal Impairment: The pharmacokinetics of clarithromycin was also altered in subjects with impaired renal function who received multiple 500-mg oral doses. The plasma levels, t½, Cmax and Cmin for both clarithromycin and its 14-OH metabolite were higher and the AUC was larger in subjects with renal impairment than its normal subjects. The extent to which these parameters differed was correlated with the degree of renal impairment; the more severe the renal impairment, the more significant the difference.
Elderly Subjects: In a comparative study of healthy, young adults and healthy, elderly subjects given multiple 500-mg oral doses of clarithromycin, the circulating plasma levels were higher and elimination was slower in the elderly group compared to the younger group. However, there was no difference between the 2 groups when renal clearance of clarithromycin was correlated with creatinine clearance. It was concluded from these results that any effect on the handling of clarithromycin is related to renal function and not subject to age.
Patients with Mycobacterial Infections: Steady-state concentrations of clarithromycin and 14-OH-clarithromycin observed following administration of usual doses to patients with HIV infections were similar to those observed in normal subjects. However, at the higher doses which may be required to treat mycobacterial infections, clarithromycin concentrations can be much higher than those observed at usual doses. In children with HIV infection taking clarithromycin 15-30 mg/kg/day in 2 divided doses, steady-state Cmax values generally ranged from 8-20 mcg/mL. However, Cmax values as high as 23 mcg/mL have been observed in HIV-infected pediatric patients taking 30 mg/kg/day in 2 divided doses as clarithromycin pediatric suspension. Elimination half-lives appeared to be lengthened at these higher doses as compared to that observed with usual doses in normal subjects. The higher plasma concentrations and longer elimination half-lives observed at these doses are consistent with the known nonlinearity in clarithromycin pharmacokinetics.
Microbiology: Clariget: Clarithromycin exerts its antibacterial action by binding to the 50S ribosomal subunits of susceptible bacteria and suppresses protein synthesis.
Clarithromycin has demonstrated excellent in vitro activity against both standard strains of bacteria and clinical isolates. It is highly potent against a wide variety of aerobic and anaerobic gram-positive and gram-negative organisms. The minimum inhibitory concentrations (MICs) of clarithromycin are generally 1 log2 dilution more potent than the MICs of erythromycin.
Clarithromycin is reported to be more active than erythromycin against susceptible streptococci and staphylococci in vitro as well as against some other species including Moraxella catarrhalis (Branhamella catarrhalis), Legionella spp, Chlamydia trachomatis and Ureaplasma urealyticum. Clarithromycin is reported to be more active than erythromycin or azithromycin against some mycobacteria including Mycobacterium avium complex and against M. leprae. It is reported to have some in vitro activity against the protozoan Toxoplasma gondii and may have some activity against cryptosporidia. The major metabolite 14-hydroxyclarithromycin is also active, and may enhance the activity of clarithromycin in vivo, notably against Haemophilus influenzae.
In vitro data also indicates that clarithromycin has excellent activity against Legionella pneumophila and Mycoplasma pneumoniae. It is bactericidal to Helicobacter pylori; this activity of clarithromycin is greater at neutral pH than at acid pH. In vitro and in vivo data show that this antibiotic has activity against clinically significant mycobacterial species.
Clariget OD: Clarithromycin has shown to be active against the following microorganisms: Aerobic Gram-positive Microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Listeria monocytogenes.
Aerobic Gram-negative Microorganisms: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Legionella spp (eg, Legionella pneumophila).
Anaerobes: Clostridium perfringens, Peptococcus sp, Peptostreptococcus sp, Propionibacterium acnes.
Mycobacteria: Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium chelonae, Mycobacterium fortuitum, MAC (consisting of Mycobacterium avium, Mycobacterium intracellulare).
Other Microorganisms: Mycoplasma pneumoniae, Chlamydia pneumonia (TWAR), Chlamydia trachomatis, Ureaplasma urealyticum.
MedsGo Class
Macrolides
Features
Brand
Clariget
Full Details
Dosage Strength
125mg / 5mL
Drug Ingredients
- Clarithromycin
Drug Packaging
Granule for Suspension 25ml
Generic Name
Clarithromycin
Dosage Form
Granule for Suspension
Registration Number
DR-XY31313
Drug Classification
Prescription Drug (RX)
Please sign in so that we can notify you about a reply