Clarithromycin for For Suspension

Clarithromycin is a macrolide antimicrobial indicated for mild to moderate infections caused by designated, susceptible bacteria in the following: • Acute Bacterial Exacerbation of Chronic Bronchitis in Adults (1.1)

• Acute Maxillary Sinusitis (1.2)

• Community-Acquired Pneumonia (1.3)

• Pharyngitis/Tonsillitis (1.4)

• Uncomplicated Skin and Skin Structure Infections (1.5)

• Acute Otitis Media in Pediatric Patients (1.6)

• Treatment and Prophylaxis of Disseminated Mycobacterial Infections (1.7)

Limitations of Use: To reduce the development of drug-resistant bacteria and maintain the effectiveness of clarithromycin and other antibacterial drugs, clarithromycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. (1.9) 1.1 Acute Bacterial Exacerbation of Chronic Bronchitis

Clarithromycin 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

[

see Indications and Usage (1.9)

]. 1.2 Acute Maxillary Sinusitis

Clarithromycin is indicated for the treatment of mild to moderate infections caused by susceptible isolates due to

Haemophilus influenzae,

Moraxella catarrhalis, or

Streptococcus pneumoniae

[

see Indications and Usage (1.9)

]. 1.3 Community-Acquired Pneumonia

Clarithromycin is indicated [

see Indications and Usage (1.9)

] for the treatment of mild to moderate infections caused by susceptible isolates due to: • Haemophilus influenzae

(in adults)

• Mycoplasma pneumoniae,

Streptococcus pneumoniae,

Chlamydophila pneumoniae

clarithromycin [in adults and pediatric patients] 1.4 Pharyngitis/Tonsillitis

Clarithromycin is indicated for the treatment of mild to moderate infections caused by susceptible isolates due to

Streptococcus pyogenes

as an alternative in individuals who cannot use first line therapy. 1.5 Uncomplicated Skin and Skin Structure Infections

Clarithromycin is indicated for the treatment of mild to moderate infections caused by susceptible isolates due to

Staphylococcus aureus, or

Streptococcus pyogenes. 1.6 Acute Otitis Media

Clarithromycin is indicated in pediatric patients for the treatment of mild to moderate infections caused by susceptible isolates due to

Haemophilus influenzae,

Moraxella catarrhalis, or

Streptococcus pneumoniae

[

see Clinical Studies (14.2)

]. 1.7 Treatment and Prophylaxis of Disseminated Mycobacterial Infections

Clarithromycin is indicated for the treatment of mild to moderate infections caused by susceptible isolates due to

Mycobacterium avium

or

Mycobacterium intracellulare

in patients with advanced HIV infection [

see Clinical Studies (14.1)

]. 1.9 Limitations of Use

There is resistance to macrolides in certain bacterial infections caused by

Streptococcus pneumoniae

and

Staphylococcus aureus. Susceptibility testing should be performed when clinically indicated. 1.10 Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of clarithromycin and other antibacterial drugs, clarithromycin 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.

• Hypersensitivity to clarithromycin or any macrolide drug (4.1) • Cisapride and pimozide (4.2) • History of cholestatic jaundice/hepatic dysfunction with use of clarithromycin (4.3) • Colchicine in renal or hepatic impairment (4.4) • Lomitapide, lovastatin, and simvastatin (4.5) • Ergot alkaloids (ergotamine or dihydroergotamine) (4.6) • Lurasidone (4.7) 4.1 Hypersensitivity Clarithromycin is contraindicated in patients with a known hypersensitivity to clarithromycin, erythromycin, or any of the macrolide antibacterial drugs [ see Warnings and Precautions (5.1) ]. 4.2 Cisapride and Pimozide Concomitant administration of clarithromycin with cisapride and pimozide is contraindicated [ see Drug Interactions (7) ]. 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. 4.3 Cholestatic Jaundice/Hepatic Dysfunction Clarithromycin is contraindicated in patients with a history of cholestatic jaundice or hepatic dysfunction associated with prior use of clarithromycin. 4.4 Colchicine Concomitant administration of clarithromycin and colchicine is contraindicated in patients with renal or hepatic impairment. 4.5 Lomitapide, Lovastatin, and Simvastatin Concomitant administration of clarithromycin with lomitapide is contraindicated due to potential for markedly increased transaminases [ see Warnings and Precautions (5.4) and Drug Interactions (7) ]. Concomitant administration of clarithromycin with HMG-CoA reductase inhibitors (statins) that are extensively metabolized by CYP3A4 (lovastatin or simvastatin) is contraindicated, due to the increased risk of myopathy, including rhabdomyolysis [ see Warnings and Precautions (5.4) and Drug Interactions (7) ]. 4.6 Ergot Alkaloids Concomitant administration of clarithromycin and ergotamine or dihydroergotamine is contraindicated [ see Drug Interactions (7) ]. 4.7 Lurasidone Concomitant administration of clarithromycin and lurasidone is contraindicated since it may result in an increase in lurasidone exposure and the potential for serious adverse reactions [see Drug Interactions (7)]. 4.8 Contraindications for Co-administered Drugs For information about contraindications of other drugs indicated in combination with clarithromycin, refer to their full prescribing information (contraindications section).

For information about contraindications of other drugs indicated in combination with clarithromycin, refer to their full prescribing information (contraindications section).

Drugs metabolized by CYP3A4: Serious adverse reactions have been reported in patients taking clarithromycin concomitantly with CYP3A4 substrates. These include colchicine toxicity with colchicine; markedly increased transaminases with lomitapide; rhabdomyolysis with simvastatin, lovastatin, and atorvastatin; hypoglycemia and cardiac arrhythmias (e.g., torsades de pointes) with disopyramide; and hypotension and acute kidney injury with calcium channel blockers metabolized by CYP3A4 (e.g., verapamil, amlodipine, diltiazem, nifedipine). Most reports of acute kidney injury with calcium channel blockers metabolized by CYP3A4 involved elderly patients 65 years of age or older. Use clarithromycin with caution when administered concurrently with medications that induce the cytochrome CYP3A4 enzyme. The use of clarithromycin with lomitapide, simvastatin, lovastatin, ergotamine, or dihydroergotamine is contraindicated [see Contraindications (4.5, 4.6) and Drug Interactions (7)].

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. 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 of clarithromycin and colchicine is contraindicated in patients with renal or hepatic impairment [see Contraindications (4.4) and Drug Interactions (7)].

Lomitapide: Concomitant use of clarithromycin with lomitapide is contraindicated [see Contraindications (4.5)]. Lomitapide is metabolized by CYP3A4, and concomitant treatment with clarithromycin increases the plasma concentration of lomitapide, which increases the risk of elevation in transaminases [see Drug Interactions (7)]. If treatment with clarithromycin cannot be avoided, therapy with lomitapide must be suspended during the course of treatment.

HMG-CoA Reductase Inhibitors (statins): Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated [see Contraindications (4.5)] as these statins are extensively metabolized by CYP3A4, and concomitant treatment with clarithromycin increases their plasma concentration, which increases the risk of myopathy, including rhabdomyolysis. Cases of rhabdomyolysis have been reported in patients taking clarithromycin concomitantly with these statins. If treatment with clarithromycin cannot be avoided, therapy with lovastatin or simvastatin must be suspended during the course of treatment.

Exercise caution 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.

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. Careful monitoring of glucose is recommended [see Drug Interactions (7)].

Quetiapine: 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 [see Drug Interactions (7)].

Oral Anticoagulants: 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 [see Drug Interactions (7)].

Benzodiazepines: Increased sedation and prolongation of sedation have been reported with concomitant administration of clarithromycin and triazolobenzodiazepines, such as triazolam and midazolam [see Drug Interactions (7)].

The following serious adverse reactions are described below and elsewhere in the labeling:

1. •Acute Hypersensitivity Reactions [see Warnings and Precautions (5.1)]
2. •QT Prolongation [see Warnings and Precautions (5.2)]
3. •Hepatotoxicity [see Warnings and Precautions (5.3)]
4. •Serious Adverse Reactions Due to Concomitant Use with Other Drugs [see Warnings andPrecautions (5.4)]
5. •Clostridium difficile Associated Diarrhea [see Warnings and Precautions (5.6)]
6. •Exacerbation of Myasthenia Gravis [see Warnings and Precautions (5.8)]

• Severe acute hypersensitivity reactions: Discontinue clarithromycin if occurs (5.1)

• QT prolongation: Avoid clarithromycin in patients with known QT prolongation or receiving drugs known to prolong the QT interval, ventricular arrhythmia (

torsades de pointes

), hypokalemia/hypomagnesemia, significant bradycardia, or taking Class IA or III antiarrhythmics (5.2)

• Hepatotoxicity: Discontinue if signs and symptoms of hepatitis occur (5.3)

• Serious adverse reactions can occur due to drug interactions of clarithromycin with colchicine, some lipid-lowering agents, some calcium channel blockers, and other drugs (5.4)

• Risk of all-cause mortality one year or more after the end of treatment in patients with coronary artery disease. Balance this potential risk with the treatment benefits when prescribing clarithromycin in these patients (5.5)

• Clostridium difficile

associated diarrhea (CDAD): Evaluate if diarrhea occurs (5.6)

• Embryo-fetal Toxicity: Based on animal findings, clarithromycin is not recommended for use in pregnant women except in clinical circumstances where no alternative therapy is appropriate (5.7)

• Exacerbation of myasthenia gravis has been reported in patients receiving clarithromycin therapy (5.8) 5.1 Severe 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 (DRESS), Henoch-Schonlein purpura, and acute generalized exanthematous pustulosis, discontinue clarithromycin therapy immediately and institute appropriate treatment. 5.2 QT Prolongation

• Clarithromycin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Cases of

torsades de pointes

have been spontaneously reported during postmarketing surveillance in patients receiving clarithromycin. Fatalities have been reported.

Avoid clarithromycin 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 [

see

also Contraindications (4.2)]

• patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia and in patients receiving Class IA (e.g., quinidine, procainamide, disopyramide) or Class III (e.g., dofetilide, amiodarone, sotalol) antiarrhythmic agents.

Elderly patients may be more susceptible to drug-associated effects on the QT interval [

see Use in Specific Populations (8.5)

]. 5.3 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 be severe and is usually reversible. In some instances, hepatic failure with fatal outcome has been reported and generally has been associated with serious underlying diseases and/or concomitant medications. Symptoms of hepatitis can include anorexia, jaundice, dark urine, pruritus, or tender abdomen. Discontinue clarithromycin immediately if signs and symptoms of hepatitis occur. 5.4 Serious Adverse Reactions Due to Concomitant Use with Other Drugs

Drugs metabolized by CYP3A4: Serious adverse reactions have been reported in patients taking clarithromycin concomitantly with CYP3A4 substrates. These include colchicine toxicity with colchicine; markedly increased transaminases with lomitapide; rhabdomyolysis with simvastatin, lovastatin, and atorvastatin; hypoglycemia and cardiac arrhythmias (e.g.,

torsades de pointes

) with disopyramide; and hypotension and acute kidney injury with calcium channel blockers metabolized by CYP3A4 (e.g., verapamil, amlodipine, diltiazem, nifedipine). Most reports of acute kidney injury with calcium channel blockers metabolized by CYP3A4 involved elderly patients 65 years of age or older. Use clarithromycin with caution when administered concurrently with medications that induce the cytochrome CYP3A4 enzyme. The use of clarithromycin with lomitapide, simvastatin, lovastatin, ergotamine, or dihydroergotamine is contraindicated [

see Contraindications (4.5, 4.6)

and

Drug Interactions (7)

].

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. 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 of clarithromycin and colchicine is contraindicated in patients with renal or hepatic impairment [

see Contraindications (4.4)

and

Drug Interactions (7)

].

Lomitapide: Concomitant use of clarithromycin with lomitapide is contraindicated [see Contraindications (4.5)]. Lomitapide is metabolized by CYP3A4, and concomitant treatment with clarithromycin increases the plasma concentration of lomitapide, which increases the risk of elevation in transaminases [see Drug Interactions (7)]. If treatment with clarithromycin cannot be avoided, therapy with lomitapide must be suspended during the course of treatment.

HMG-CoA Reductase Inhibitors (statins): Concomitant use of clarithromycin with lovastatin or simvastatin is contraindicated [

see Contraindications (4.5)

] as these statins are extensively metabolized by CYP3A4, and concomitant treatment with clarithromycin increases their plasma concentration, which increases the risk of myopathy, including rhabdomyolysis. Cases of rhabdomyolysis have been reported in patients taking clarithromycin concomitantly with these statins. If treatment with clarithromycin cannot be avoided, therapy with lovastatin or simvastatin must be suspended during the course of treatment.

Exercise caution 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.

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. Careful monitoring of glucose is recommended [

see Drug Interactions (7)

].

Quetiapine: 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

[see Drug Interactions (7)].

Oral Anticoagulants: 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 [

see Drug Interactions (7)

].

Benzodiazepines: Increased sedation and prolongation of sedation have been reported with concomitant administration of clarithromycin and triazolobenzodiazepines, such as triazolam and midazolam [

see Drug Interactions (7)

]. 5.5 All-Cause Mortality in Patients with Coronary Artery Disease 1 to 10 Years after Clarithromycin Exposure

In one clinical trial evaluating treatment with clarithromycin on outcomes in patients with coronary artery disease, an increase in risk of all-cause mortality one year or more after the end of treatment was observed in patients randomized to receive clarithromycin.1 Clarithromycin for treatment of coronary artery disease is not an approved indication. The cause of the increased risk has not been established. Other epidemiologic studies evaluating this risk have shown variable results [see Adverse Reactions (6.1)]. Consider balancing this potential risk with the treatment benefits when prescribing clarithromycin in patients who have suspected or confirmed coronary artery disease. 5.6

Clostridium difficile

Associated Diarrhea

Clostridium difficile

associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including clarithromycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of

C. difficile.

C. difficile

produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of

C. difficile

cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. 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. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of

C. difficile, and surgical evaluation should be instituted as clinically indicated. 5.7 Embryo-fetal Toxicity

Based on findings from animal studies, clarithromycin is not recommended for use 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 demonstrated adverse effects on pregnancy outcome and/or embryo- fetal development, including fetal malformations, in pregnant animals administered oral clarithromycin [

see Use in Specific Populations (8.1)

]. 5.8 Exacerbation of Myasthenia Gravis

Exacerbation of symptoms of myasthenia gravis and new onset of symptoms of myasthenic syndrome has been reported in patients receiving clarithromycin therapy. 5.9 Development of Drug Resistant Bacteria

Prescribing clarithromycin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

• Pediatric Patients: Clarithromycin 15 mg/kg/day divided every 12 hours for 10 days (2.4) • Mycobacterial Infections: Clarithromycin 500 mg every 12 hours; Clarithromycin 7.5 mg/kg up to 500 mg every 12 hours in pediatric patients (2.5) • Reduce dose in moderate renal impairment with concomitant atazanavir or ritonavir-containing regimens and in severe renal impairment (2.6) 2.1 Important Administration Instructions Clarithromycin for oral suspension may be given with or without food. 2.4 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 [ see Dosage and Administration (2.5) ]. 2.5 Dosage Regimens for Mycobacterial Infections For the treatment of disseminated infection due to Mycobacterium avium complex (MAC), clarithromycin is recommended as the primary agents. Clarithromycin 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 [ see Clinical Studies (14.1) ]. Adult Patients For treatment and prophylaxis of mycobacterial infections in adults, the recommended dose of clarithromycin is 500 mg every 12 hours. 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. [ see Use in Specific Populations (8.4) and Clinical Studies (14.1) ]. Clarithromycin therapy should continue if clinical response is observed. Clarithromycin can be discontinued when the patient is considered at low risk of disseminated infection. 2.6 Dosage Adjustment in Patients with Renal Impairment See Table 2 for dosage adjustment in patients with moderate or severe renal impairment with or without concomitant atazanavir or ritonavir-containing regimens [ see Drug Interactions (7) ]. Table 2. Clarithromycin Dosage Adjustments in Patients with Renal Impairment • Recommended ClarithromycinDosage Reduction • Patients with severe renal impairment (CLcr of <30 mL/min) • Reduce the dosage of Clarithromycin by 50% • Patients with moderate renal impairment (CLcr 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 (CLcr of <30 mL/min) taking concomitant atazanavir or ritonavir-containing regimens • Reduce the dosage of Clarithromycin by 75% 2.7 Dosage Adjustment Due to Drug Interactions Decrease the dose of clarithromycin by 50 % when co-administered with atazanavir [ see Drug Interactions (7) ]. Dosage adjustments for other drugs when co-administered with clarithromycin may be recommended due to drug interactions [ see Drug Interactions (7) ]. 2.8 Reconstitution of Clarithromycin for Oral Suspension The supplied clarithromycin granules must be reconstituted with water prior to administration of clarithromycin for oral suspension. Table 3 below indicates the volume of water to be added when reconstituting. To reconstitute: • a. Add half the volume of water to the bottle containing the clarithromycin granules and shake vigorously. • b. Add the remainder of water to the bottle and shake. Shake well before each use. After mixing, store at 15° to 30°C (59° to 86°F) and use within 14 days. Do not refrigerate. Table 3. Volume of Water to be Added When Reconstituting Clarithromycin Granules Total Volume After Reconstitution Clarithromycin Concentration After Reconstitution Amount of Water to be Added 50 mL 125 mg/5 mL 29.5 mL 100 mL 125 mg/5 mL 59 mL 50 mL 250 mg/5 mL 28.5 mL 100 mL 250 mg/5 mL 57 mL

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 [see Dosage and Administration (2.5)].

For the treatment of disseminated infection due to Mycobacterium avium complex (MAC), clarithromycin is recommended as the primary agents. Clarithromycin 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 [see Clinical Studies (14.1)].

Adult Patients

For treatment and prophylaxis of mycobacterial infections in adults, the recommended dose of clarithromycin is 500 mg every 12 hours.

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. [see Use in Specific Populations (8.4) and Clinical Studies (14.1)].

Clarithromycin therapy should continue if clinical response is observed. Clarithromycin can be discontinued when the patient is considered at low risk of disseminated infection.

See Table 2 for dosage adjustment in patients with moderate or severe renal impairment with or without concomitant atazanavir or ritonavir-containing regimens [see Drug Interactions (7) ].

Table 2. Clarithromycin Dosage Adjustments in Patients with Renal Impairment

Decrease the dose of clarithromycin by 50 % when co-administered with atazanavir [see Drug Interactions (7)]. Dosage adjustments for other drugs when co-administered with clarithromycin may be recommended due to drug interactions [see Drug Interactions (7)].

Clarithromycin is available as:

1.  • Clarithromycin for oral suspension (white to off-white granules before reconstitution; white to off-white opaque suspension after reconstitution):
2.  ◦ 125 mg/5 mL concentration available in 50 mL and 100 mL bottles
3.  ◦ 250 mg/5 mL concentration available in 50 mL and 100 mL bottles

Decrease the dose of clarithromycin by 50 % when co-administered with atazanavir [see Drug Interactions (7)]. Dosage adjustments for other drugs when co-administered with clarithromycin may be recommended due to drug interactions [see Drug Interactions (7)].

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, especially if the CYP3A substrate has a narrow safety margin (e.g., carbamazepine) and/or the substrate is extensively metabolized by this enzyme. Adjust dosage when appropriate and monitor serum concentrations of drugs primarily metabolized by CYP3A closely in patients concurrently receiving clarithromycin.

Table 8: Clinically Significant Drug Interactions with Clarithromycin