Composition:
Each film coated tablet contains 250 or 500mg Clarithromycin.
Mechanism of Action:
Clarithromycin is a macrolide antimicrobial drug; it exerts its antibacterial action by binding to the 50S ribosomal subunit of susceptible bacteria resulting in inhibition of protein synthesis.
Pharmacokinetics:
Absorption: The absolute bioavailability of 250 mg clarithromycin tablets was approximately 50%. In non-fasting healthy subjects peak plasma concentrations were attained within 2 to 3 hours after oral dosing.
Distribution: Clarithromycin and its metabolite distribute readily into body tissues and fluids.
Metabolism and Elimination: The elimination half-life of clarithromycin was about 3 hours to 4 hours with 250 mg administered every 12 hours but increased to 5 hours to 7 hours with 500 mg administered every 8 hours to 12 hours.
Indications:
1- Acute Bacterial Exacerbation of Chronic Bronchitis: it is indicated in adults for the treatment of mild to moderate infections caused by susceptible isolates due to Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, or Streptococcus pneumoniae.
2- Acute Maxillary Sinusitis: it is indicated in adults for the treatment of mild to moderate infections caused bysusceptible isolates due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumonia.
3- Community-Acquired Pneumonia: it is indicated for the treatment of mild to moderate infections caused by susceptible isolates due to: Haemophilus influenzae (in adults) Mycoplasma pneumoniae, Streptococcus pneumoniae, Chlamydophila pneumoniae (in adults and pediatric patients).
4- Pharyngitis /Tonsillitis: it is indicated for thetreatment of mild to moderate infections caused by susceptible isolates due to Streptococcus pyogenes asan alternative in individuals who cannot use first line therapy.
5- Uncomplicated Skin and Skin Structure Infections: it is indicated for thetreatment of mild to moderate infections caused by susceptible isolates due to Staphylococcus aureus, or Streptococcus pyogenes.
6- Acute Otitis Media: it is indicated in pediatricpatients for the treatment of mild to moderate infections caused by susceptible isolates due toHaemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumonia.
7- Treatment and Prophylaxis of Disseminated Mycobacterial Infections: it is indicated for the treatment of mild to moderate infections caused by susceptible isolates due to Mycobacterium avium orMycobacterium intracellulare in patients with advanced HIV infection.
8- Helicobacter pylori Infection and Duodenal Ulcer Disease: the Tablets are given in combination with other drugs in adults as described below toeradicate H. pylori. The eradication of H. pylori has been demonstrated to reduce the risk of duodenalulcer recurrence.
• Clarithromycin Tablets in combination with amoxicillin and lansoprazole or 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.
• Clarithromycin Tablets in combination with omeprazole capsules are indicated for the treatment of patients with an active duodenal ulcer associated with H. pylori infection.
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.
Limitations of Use:
•There is resistance to macrolides in certain bacterial infections caused by Streptococcus pneumoniae and Staphylococcus aureus. Susceptibility testing should be performed to reduce the development of drug-resistant bacteria and maintain the effectiveness of clarithromycin and other antibacterial drugs and it 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.
Contraindications:
• It is contraindicated in patients with a known hypersensitivity to clarithromycin, erythromycin, or any of the macrolide antibacterial drugs.
• Concomitant administration of clarithromycin with cisapride and pimozide is contraindicated. There have been postmarketing reports of drug interactions when clarithromycin is co-administered with cisapride or pimozide, 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 clarithromycin. Fatalities have been reported.
• Clarithromycin is contraindicated in patients with a history of cholestatic jaundice or hepatic dysfunction associated with prior use of clarithromycin.
• Concomitant administration of clarithromycin and colchicine is contraindicated in patients with renal or hepatic impairment.
• Use of clarithromycin concomitantly with HMG-CoA reductase inhibitors (statins) that are extensively metabolized by CYP3A4 (lovastatin or simvastatin), due to the increased risk of myopathy, including rhabdomyolysis.
• Concomitant administration of clarithromycin and ergotamine or dihydroergotamine is contraindicated
For information about contraindications of other drugs indicated in combination with clarithromycin refer to their full prescribing information.
Warnings and precautions:
- Acute Hypersensitivity Reactions:In the event of severe acute hypersensitivity reactions, such as anaphylaxis, Stevens - Johnson syndrome,toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms and Henoch-Schonlein purpura, discontinue clarithromycin therapy immediately and institute appropriate treatment.
- QT Prolongation:Clarithromycin has been associated with prolongation of the QT interval and infrequent cases ofarrhythmia. Fatalities have been reported.
Clarithromycin should be avoided in the following patients:
• Patients with known prolongation of the QT interval, ventricular cardiac arrhythmia, including torsades de pointes
• Patients receiving drugs known to prolong the QT interval.
• Patients with ongoing pro-arrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia and in patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents.
Elderly patients may be more susceptible to drug-associated effects on the QT interval.
- Hepatotoxicity: Hepatic dysfunction, including increased liver enzymes, and hepatocellular and/or cholestatic hepatitis,with or without jaundice, has been reported with clarithromycin. This hepatic dysfunction may besevere and is usually reversible. In some instances, hepatic failure with fatal outcome has been reported.
Symptoms of hepatitis can include anorexia, jaundice, dark urine, pruritus, or tender abdomen. Discontinue clarithromycin immediately if signs and symptoms of hepatitis occur.
- Clostridium difficile Associated Diarrhea:Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterialagents, including clarithromycin, and may range in severity from mild diarrhea to fatal colitis. Treatmentwith antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued.
- Exacerbation of Myasthenia Gravis: Exacerbation of symptoms of myasthenia gravis and new onset of symptoms of myasthenic syndrome hasbeen reported in patients receiving clarithromycin therapy.
- Development of Drug Resistant Bacteria:Prescribing clarithromycin in the absence of a proven or strongly suspected bacterial infection or aprophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Adverse reaction:
The most frequent adverse reactions for both adult and pediatric patients observed in clinical trials are abdominal pain, diarrhea, nausea, vomiting and dysgeusia. Also reported were dyspepsia, liver function test abnormal, anaphylactic reaction, candidiasis, headache, insomnia, and rash.
Adverse Reactions in Immunocompromised Adult Patients Receiving Prophylaxis against M. avium Complex: Abdominal pain, Headache, Diarrhea, Dyspepsia, Flatulence, Nausea, Vomiting, Rash, Taste Perversion, and SGOT increases, SGPT increases. Primary reasons for discontinuation in clarithromycin treated patients include headache, nausea, and vomiting, depression, and taste perversion.
Adverse Reactions in patient with Duodenal ulcer associated with H. pylori Infection with an Incidence of 3% or Greater: Abdominal pain, Headache, Diarrhea, Nausea, Vomiting, , Taste Perversion, Infection.
Pregnancy:
Teratogenic Effects, Category C.
Clarithromycin should not be used in pregnant women except in clinical circumstances where no alternative therapy is appropriate. If clarithromycin is used during pregnancy, or if pregnancy occurs while the patient is taking this drug, the patient should be apprised of the potential hazard to the fetus.
Clarithromycin has demonstrated adverse effects on pregnancy outcome and/or fetal development in monkeys, rats, mice, and rabbits at doses that produced plasma levels 2 times to 17 times the serum levels achieved in humans treated at the maximum recommended human doses.
Lactation:
Caution should be exercised when clarithromycin is administered to nursing women. The development and health benefits of human milk feeding should be considered along with the mother’s clinical need for clarithromycin and any potential adverse effects on the human milk fed child from the drug or from the underlying maternal condition.
Clarithromycin and its active metabolite are excreted in human milk.
Adverse reactions occurred in 12.7% of infants exposed to macrolides and included rash, diarrhea, loss of appetite, and somnolence.
Pediatric Use:
The safety and effectiveness of Clarithromycin Tablets and granules for Oral Suspension have been established for the treatment of the following conditions or diseases in pediatric patients 6 months and older: Pharyngitis/Tonsillitis, Community-Acquired Pneumonia, Acute maxillary sinusitis, Acute otitis media, Uncomplicated skin and skin structure infections.
The safety and effectiveness of Clarithromycin Tablets and granules for Oral Suspension have been established for the prevention of disseminated Mycobacterium avium complex (MAC) disease in pediatric patients 20 months and older with advanced HIV infection.
The safety and effectiveness of Clarithromycin Extended-Release Tablets in the treatment of pediatric patients has not been established.
Safety and effectiveness of clarithromycin in pediatric patients under 6 months of age have not been established.
The safety of clarithromycin has not been studied in MAC patients under the age of 20 months.
Geriatric Use:
In clinical trials, elderly patients did not have an increased incidence of adverse reactions when compared to younger patients. Consider dosage adjustment in elderly patients with severe renal impairment.
Elderly patients may be more susceptible to development of torsades de pointes arrhythmias than younger patients.
Most reports of acute kidney injury with calcium channel blockers metabolized by CYP3A4 involved elderly patients 65 years of age or older.
Renal and Hepatic Impairment:
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.
Drug Interactions:
Co-administration of clarithromycin is known to inhibit CYP3A, and a drug primarily metabolized by CYP3A may be associated with elevations in drug concentrations that could increase or prolong both therapeutic and adverse effects of the concomitant drug.
Clarithromycin should be used with caution in patients receiving treatment with other drugs known to be CYP3A enzyme substrates. Adjust dosage when appropriate and monitor serum concentrations of drugs primarily metabolized by CYP3A closely in patients concurrently receiving clarithromycin.
1- Drugs metabolized by CYP3A4: Serious adverse reactions have been reported in patients takingclarithromycin concomitantly with CYP3A4 substrates. These include colchicine toxicity withcolchicine, rhabdomyolysis with simvastatin, lovastatin, and atorvastatin; hypoglycemia withdisopyramide; hypotension and acute kidney injury with calcium channel blockers metabolized byCYP3A4 (e.g., verapamil, amlodipine, diltiazem, nifedipine)
Colchicine: 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. Colchicine is a substrate for both CYP3A and the P-glycoprotein (Pgp). Clarithromycin and other macrolides are known to inhibit CYP3A and Pgp. If co-administration of clarithromycin and colchicine is necessary in patients with normal renal and hepatic function, reduce the dose of colchicine. Monitor patients for clinical symptoms of colchicine toxicity. Concomitant administration is contraindicated in patients with renal or hepatic impairment.
HMG-CoA Reductase Inhibitors (statins): Concomitant use of clarithromycin with lovastatin orsimvastatin is contraindicated as these statins are extensively metabolizedby CYP3A4, and concomitant treatment with clarithromycin increases their plasma concentration, whichincreases the risk of myopathy, including rhabdomyolysis. If treatment with clarithromycin cannotbe avoided, therapy with lovastatin or simvastatin must be suspended during the course of treatment.
Caution should be exercised when prescribing clarithromycin with atorvastatin or pravastatin. In situations where the concomitant use of clarithromycin with atorvastatin or pravastatin cannot be avoided, atorvastatin dose should not exceed 20 mg daily and pravastatin dose should not exceed 40 mg daily. Use of a statin that is not dependent on CYP3A metabolism (e.g. fluvastatin) can be considered. It is recommended to prescribe the lowest registered dose if concomitant use cannot be avoided.
Antiarrhythmics (Disopyramide, Quinidine, Dofetilide, Amiodarone, Sotalol, and Procainamide): there have been postmarketing reports of torsades de pointes occurring with concurrent use of clarithromycin and quinidine or disopyramide. Electrocardiograms should be monitored for QTc prolongation during coadministration of clarithromycin with these drugs. Serum concentrations of these medications should also be monitored. There have been postmarketing reports of hypoglycemia with the concomitant administration of clarithromycin and disopyramide. Therefore, blood glucose levels should be monitored during concomitant administration of clarithromycin and disopyramide, the concomitant use is Not Recommended.
Calcium Channel Blockers:
• Verapamil: it should be used with Caution. Hypotension, bradyarrhythmias, and lactic acidosis have been observed in patients receiving concurrent verapamil,
• Nifedipine: Nifedipine is a substrate for CYP3A. Clarithromycin and other macrolides are known to inhibit CYP3A. There is potential of CYP3A-mediated interaction between nifedipine and clarithromycin. Hypotension and peripheral edema were observed when clarithromycin was taken concomitantly with nifedipine; it should be used with Caution.
Oral Hypoglycemic Agents/Insulin: The concomitant use of clarithromycin and oral hypoglycemic agents and/or insulin can result in significant hypoglycemia. With certain hypoglycemic drugs such as nateglinide, pioglitazone, repaglinide and rosiglitazone, inhibition of CYP3A enzyme by clarithromycin may be involved and could cause hypoglycemia when used concomitantly. It should be used with caution and Careful monitoring of glucose is recommended.
Antipsychotics (Quetiapine): Quetiapine is a substrate for CYP3A4, which is inhibited by clarithromycin. Use quetiapine and clarithromycin concomitantly with caution. Co-administration could result in increased quetiapine exposure and quetiapine related toxicities such as somnolence, orthostatic hypotension, altered state of consciousness, neuroleptic malignant syndrome, and QT prolongation. Refer to quetiapine prescribing information for recommendations on dose reduction if co-administered with CYP3A4 inhibitors such as clarithromycin.
Oral Anticoagulants (Warfarin): there is a risk of serious hemorrhage and significant elevations in INR and prothrombin time when clarithromycin is co-administered with warfarin. Monitor INR and prothrombin times frequently while patients are receiving clarithromycin and oral anticoagulants concurrently, it should be used with Caution.
Benzodiazepines:
Increased sedation and prolongation of it have been reported with concomitant administration of clarithromycin and benzodiazepines, such as triazolam and midazolam.
• Midazolam: When oral midazolam is co-administered with clarithromycin, dose adjustments may be necessary and possible prolongation and intensity of effect should be anticipated, therefor it should be used with Caution.
• Triazolam, Alprazolam: appropriate dose adjustments should be considered when triazolam or alprazolam is co-administered with clarithromycin. There have been postmarketing reports of drug interactions and central nervous system (CNS) effects with the concomitant use of clarithromycin and triazolam. Monitoring the patient for increased CNS pharmacological effects is suggested; therefor it should be used with Caution.
• Temazepam, Nitrazepam, Lorazepam: For benzodiazepines which are not metabolized by CYP3A (e.g., temazepam, nitrazepam, lorazepam), a clinically important interaction with clarithromycin is unlikely, therefor No Dose Adjustment is needed.
Digoxin: Digoxin is a substrate for P-glycoprotein (Pgp) and clarithromycin is known to inhibit Pgp. When clarithromycin and digoxin are co-administered, inhibition of Pgp by clarithromycin may lead to increased exposure of digoxin. Monitoring of serum digoxin concentrations should be considered and it should be used with Caution.
Antiepileptics (Carbamazepine): 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. Increased serum concentrations of carbamazepine were observed in clinical trials with clarithromycin. There have been published reports of CYP3A based interactions of clarithromycin with carbamazepine. Therefore, it should be used with Caution.
Antifungals:
• Itraconazole: Both clarithromycin and itraconazole are substrates and inhibitors of CYP3A, potentially leading to a bi-directional drug interaction when administered concomitantly. Clarithromycin may increase the plasma concentrations of itraconazole and Itraconazole may increase the plasma concentrations of clarithromycin, Patients taking itraconazole and clarithromycin concomitantly should be monitored closely for signs or symptoms of increased or prolonged adverse reactions. The concomitant administration should be used with Caution.
• Fluconazole: No Dose Adjustment.
Antispasmodics (Tolterodine in patients deficient in CYP2D6 activity): The primary route of metabolism for tolterodine is via CYP2D6. However, in a subset of the patient devoid of CYP2D6, the identified pathway of metabolism is via CYP3A. In this patient, inhibition of CYP3A results in significantly higher serum concentrations of tolterodine. Tolterodine 1 mg twice daily is recommended in patients deficient in CYP2D6 activity (poor metabolizers) when co-administered with clarithromycin; therefore, it should be used with Caution.
Ergot Alkaloids (ergotamine, Dihydroergotamine): Postmarketing reports indicate that coadministration of clarithromycin with ergotamine or dihydroergotamine has been associated with acute ergot toxicity, therefor it is contraindicated.
Immunosuppressants (Cyclosporine, Tacrolimus): There have been published reports of CYP3A based interactions of clarithromycin with cyclosporine and with tacrolimus. Therefore, it should be used With Caution.
Phosphodiesterase inhibitors: Sildenafil, Tadalafil, Vardenafil: Each of these phosphodiesterase inhibitors is primarily metabolized by CYP3A, and CYP3A will be inhibited by concomitant administration of clarithromycin. Coadministration with clarithromycin will result in increased exposure of these phosphodiesterase inhibitors. Coadministration with clarithromycin is not recommended. Reduction of dosage for phosphodiesterase inhibitors should be considered, and it should be used With Caution.
Proton Pump Inhibitors (Omeprazole): Clarithromycin concentrations in the gastric tissue and mucus were also increased by concomitant administration of omeprazole; it should be used With Caution.
Xanthine Derivatives (Theophylline): 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, it should be used With Caution.
Antivirals: Doses of clarithromycin greater than 1000 mg per day should not be co-administered with protease inhibitors
• Atazanavir: Both clarithromycin and atazanavir are substrates and inhibitors of CYP3A, and there is evidence of a bi-directional drug interaction. When clarithromycin is co-administered with atazanavir, the dose of clarithromycin should be decreased by 50%, since concentrations of 14-OH clarithromycin are significantly reduced when clarithromycin is coadministered with atazanavir, alternative antibacterial therapy should be considered for indications other than infections due to Mycobacterium avium complex, It should be used With Caution.
• Ritonavir (in patients with decreased renal function): Since concentrations of 14-OH clarithromycin are significantly reduced when clarithromycin is co-administered with ritonavir, alternative antibacterial therapy should be considered for indications other than infections due to Mycobacterium avium, It should be used With Caution.
• Saquinavir (in patients with decreased renal function): When saquinavir is co-administered with ritonavir, consideration should be given to the potential effects of ritonavir on clarithromycin, Both clarithromycin and saquinavir are substrates and inhibitors of CYP3A and there is evidence of a bi-directional drug interaction, It should be used With Caution.
• Etravirine: Clarithromycin exposure was decreased by etravirine; however, concentrations of the active metabolite, 14-OH-clarithromycin, were increased. Because 14-OH-clarithromycin has reduced activity against Mycobacterium avium complex (MAC), overall activity against this pathogen may be altered; therefore alternatives to clarithromycin should be considered for the treatment of MAC. It should be used With Caution
• Maraviroc: Clarithromycin may result in increases in maraviroc exposures by inhibition of CYP3A metabolism. See Maraviroc prescribing information for dose recommendations when given with strong CYP3A inhibitors such as clarithromycin. It should be used With Caution
• Boceprevir (in patients with normal renal function): Both clarithromycin and boceprevir are substrates and inhibitors of CYP3A, potentially leading to a bi-directional drug interaction when coadministered. No dose adjustments are necessary for patients with normal renal function (see Boceprevir prescribing information).
• Didanosine, Saquinavir (in patients with normal renal function), Ritonavir (in patients with normal renal function): No Dose Adjustment.
• Zidovudine: Simultaneous oral administration of clarithromycin immediate-release tablets and zidovudine to HIV-infected adult patients may result in decreased steady-state zidovudine concentrations. Administration of clarithromycin and zidovudine should be separated by at least two hours. The impact of co-administration of clarithromycin extended-release tablets or granules and zidovudine has not been evaluated.
2- Other Drugs Metabolized by CYP3A: There have been published reports of CYP3A based interactions of clarithromycin with alfentanil, methylprednisolone, cilostazol, bromocriptine, vinblastine, phenobarbital, and St. John’s Wort; it should be used With Caution.
3- Other Drugs Metabolized by CYP450 Other than CYP3A: There have been postmarketing reports of interactions of clarithromycin with drugs not thought to be metabolized by CYP3A, including hexobarbital, phenytoin, and valproate; it should be used With Caution.
4- Inducers of CYP3A enzymes: Inducers such as efavirenz, nevirapine, rifampicin, rifabutin, and rifapentine will increase the metabolism of clarithromycin. Alternative antibacterial treatment should be considered when treating patients receiving inducers of CYP3A. if the conocimtant use is indicated it should be used with caution.
5- Cytochrome P450 Inducers: Concomitant administration of rifabutin and clarithromycin resulted in an increase in rifabutin, and decrease in clarithromycin serum levels together with an increased risk of uveitis, There have been published reports of CYP3A based interactions of clarithromycin with rifabutin, : It should be used With Caution
Dosage and administration:
Clarithromycin Tablets may be given with or without food.
Adult Dosage: for the treatment of mild to moderate infections in adults
|
|
Tablets |
|
|
infection |
Dosage(every 12 hours ) |
Duration ( days) |
|
Acute bacterial exacerbation of chronic bronchitis |
250 to 500 mg (For M. catarrhalis and S. pneumoniae use 250 mg, For H. influenzae and H. parainfluenzae, use 500 mg) |
7-14 (For H parainfluenzae, the duration of therapy is 7 days) |
|
Acute maxillary sinusitis
|
500 mg |
14 |
|
Community-acquired pneumonia
|
250 mg For H. parainfluenzae and M. catarrhalis use the Extended-Release Tablets only |
7-14 For H. influenzae, the duration of therapy is 7 days |
|
Pharyngitis/Tonsillitis |
250 mg |
10 |
|
Uncomplicated skin and skin structure infections |
250 mg |
7-14 |
|
Treatment and prophylaxis of disseminated Mycobacterium avium disease |
500 mg Clarithromycin therapy should continue if clinical response is observed. It can be discontinued when the patient is considered at low risk of disseminated infection |
- |
|
H.pylori eradication to reduce the risk of duodenal ulcer recurrence with amoxicillin and omeprazole or lansoprazole |
500 mg |
10-14 |
|
H.pylori eradication to reduce the risk of duodenal ulcer recurrence with omeprazole |
500 mg every 8 hours |
14 |
Combination Dosing Regimens for H. pylori Infection:
1- Triple therapy: Clarithromycin Tablets/lansoprazole/amoxicillin: The recommended adult dosage is 500 mg Clarithromycin, 30 mg lansoprazole, and 1 gram amoxicillin, all given every 12 hours for 10 or 14 days.
2- Triple therapy: Clarithromycin Tablets/omeprazole/amoxicillin:The recommended adult dosage is 500 mg Clarithromycin, 20 mg omeprazole, and 1 gram amoxicillin; all given every 12 hours for 10 days. 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.
3- Dual therapy: Clarithromycin Tablets/omeprazole: The recommended adult dosage is 500 mg Clarithromycin given every 8 hours and 40 mg omeprazole given once every morning for 14 days. An additional 14 days of omeprazole 20 mg once daily is recommended for ulcer healing and symptom relief.
Pediatric Dosage: The recommended daily dosage is 15 mg/kg/day divided every 12 hours for 10 days (up to the adult dose). Refer to dosage regimens for mycobacterial infections in pediatric patients for additional dosage information.
Dosage Regimens for Mycobacterial Infections:
For the treatment of disseminated infection due to Mycobacterium avium complex (MAC)
Clarithromycin Tablets and granules for Oral Suspension are recommended as the primary agents. Clarithromycin Tablets and granules for Oral Suspension should be used in combination with other antimycobacterial drugs (e.g. ethambutol) that have shown in vitro activity against MAC or clinical benefit in MAC treatment.
1- Adult Patients: For treatment and prophylaxis of mycobacterial infections in adults, the recommended dose of clarithromycin is 500 mg every 12 hours.
2- Pediatric Patients: For treatment and prophylaxis of mycobacterial infections in pediatric patients, the recommended dose is 7.5 mg/kg every 12 hours up to 500 mg every 12 hours. Clarithromycin therapy should continue if clinical response is observed. It can be discontinued when the patient is considered at low risk of disseminated infection.
Dosage Adjustment in Patients with Renal Impairment:
Recommended Clarithromycin Dosage Reduction
Patients with severe renal impairment (CL of <30 mL/min): Reduce the dosage of
clarithromycin by 50%
Patients with moderate renal impairment (CL of 30 to 60 mL/min) taking
concomitant atazanavir or ritonavir-containing regimens: Reduce the dosage of
clarithromycin by 50%
Patients with severe renal impairment (CL of <30 mL/min) taking
concomitant atazanavir or ritonavir-containing regimen: Reduce the dosage of
clarithromycin by 75%
Dosage Adjustment Due to Drug Interactions: Decrease the dose of clarithromycin by 50 % when co-administered with atazanavir. Dosage adjustments for other drugs when co-administered with clarithromycin may be recommended due to drug interactions.
Overdosage:
Overdosage of clarithromycin can cause gastrointestinal symptoms such as abdominal pain, vomiting, nausea, and diarrhea.
Treat adverse reactions accompanying overdosage 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.