What is mechanism of action?

mechanism of action is Cytochrome P450 3A Inhibitors [MoA], P-Glycoprotein Inhibitors [MoA] or Cytochrome P450 3A4 Inhibitors [MoA]

Clarithromycin

Check Drug InteractionsCheck known drug interactions.

Check Drug Interactions

Clarithromycin Prescribing Information

Hypersensitivity to clarithromycin or any macrolide drug

Cisapride and pimozide

History of cholestatic jaundice/hepatic dysfunction with use of clarithromycin

Colchicine in renal or hepatic impairment

Lomitapide, lovastatin, and simvastatin

Ergot alkaloids (ergotamine or dihydroergotamine)

Lurasidone

4.1 Hypersensitivity

Clarithromycin tablets are contraindicated in patients with a known hypersensitivity to clarithromycin, erythromycin, or any of the macrolide antibacterial drugs

[see Warnings and Precautions ]

4.2 Cisapride and Pimozide

Concomitant administration of clarithromycin tablets with cisapride and pimozide is contraindicated

[see Drug Interactions ]

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 tablets. Fatalities have been reported.

4.3 Cholestatic Jaundice/Hepatic Dysfunction

Clarithromycin tablets are 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 tablets and colchicine is contraindicated in patients with renal or hepatic impairment.

4.5 Lomitapide, Lovastatin, and Simvastatin

Concomitant administration of clarithromycin tablets with lomitapide is contraindicated due to potential for markedly increased transaminases

[see Warnings and Precautions and Drug Interactions ].

Concomitant administration of clarithromycin tablets 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 and Drug Interactions ].

4.6 Ergot Alkaloids

Concomitant administration of clarithromycin and ergotamine or dihydroergotamine is contraindicated

[see Drug Interactions ]

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

4.8 Contraindications for Co-administered Drugs

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

)

Contraindications (

4 CONTRAINDICATIONS

05/2023

Drug Interactions (

7 DRUG INTERACTIONS

Co-administration of clarithromycin tablets 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 tablets 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 Tablets
Drugs That Are Affected By Clarithromycin Tablets
Drug(s) with Pharmacokinetics Affected by Clarithromycin Tablets	Recommendation	Comments
Antiarrhythmics:
Disopyramide Quinidine Dofetilide Amiodarone Sotalol Procainamide	Not Recommended	Disopyramide, Quinidine: 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 [see Warnings and Precautions ( 5.2 )] . Serum concentrations of these medications should also be monitored. There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with disopyramide and quinidine. 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.
Digoxin	Use With Caution	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. Elevated digoxin serum concentrations in patients receiving clarithromycin and digoxin concomitantly have been reported in postmarketing surveillance. Some patients have shown clinical signs consistent with digoxin toxicity, including potentially fatal arrhythmias. Monitoring of serum digoxin concentrations should be considered, especially for patients with digoxin concentrations in the upper therapeutic range.
Oral Anticoagulants:
Warfarin	Use With Caution	Oral anticoagulants: Spontaneous reports in the postmarketing period suggest that concomitant administration of clarithromycin and oral anticoagulants may potentiate the effects of the oral anticoagulants. Prothrombin times should be carefully monitored while patients are receiving clarithromycin and oral anticoagulants simultaneously [see Warnings and Precautions ] .
Antiepileptics:
Carbamazepine	Use With Caution	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 spontaneous or published reports of CYP3A based interactions of clarithromycin with carbamazepine.
Antifungals:
Itraconazole	Use With Caution	Itraconazole: Both clarithromycin and itraconazole are substrates and inhibitors of CYP3A, potentially leading to a bi-directional drug interaction when administered concomitantly (see also Itraconazole under “Drugs That Affect Clarithromycin Tablets” in the table below). Clarithromycin may increase the plasma concentrations of itraconazole. Patients taking itraconazole and clarithromycin concomitantly should be monitored closely for signs or symptoms of increased or prolonged adverse reactions.
Fluconazole	No Dose Adjustment	Fluconazole: [see Pharmacokinetics ]
Anti-Gout Agents:
Colchicine (in patients with renal or hepatic impairment)	Contraindicated	Colchicine: Colchicine is a substrate for both CYP3A and the efflux transporter, P-glycoprotein (Pgp). Clarithromycin and other macrolides are known to inhibit CYP3A and Pgp. The dose of colchicine should be reduced when co-administered with clarithromycin in patients with normal renal and hepatic function [see Contraindications and Warnings and Precautions ] .
Colchicine (in patients with normal renal and hepatic function)	Use With Caution
Antipsychotics:
Pimozide	Contraindicated	Pimozide: [See Contraindications ]
Quetiapine Lurasidone		Quetiapine: Quetiapine is a substrate for CYP3A4, which is inhibited by clarithromycin. Co‑administration with clarithromycin could result in increased quetiapine exposure and possible quetiapine related toxicities. There have been postmarketing reports of somnolence, orthostatic hypotension, altered state of consciousness, neuroleptic malignant syndrome, and QT prolongation during concomitant administration. Refer to quetiapine prescribing information for recommendations on dose reduction if co‑administered with CYP3A4 inhibitors such as clarithromycin. Lurasidone: [See Contraindications ]
Antispasmodics:
Tolterodine (patients deficient in CYP2D6 activity)	Use With Caution	Tolterodine: The primary route of metabolism for tolterodine is via CYP2D6. However, in a subset of the population devoid of CYP2D6, the identified pathway of metabolism is via CYP3A. In this population subset, 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.
Antivirals:
Atazanavir	Use With Caution	Atazanavir: Both clarithromycin and atazanavir are substrates and inhibitors of CYP3A, and there is evidence of a bi-directional drug interaction (see Atazanavir under “Drugs That Affect Clarithromycin Tablets” in the table below) [see Pharmacokinetics ] .
Saquinavir (in patients with decreased renal function)		Saquinavir: Both clarithromycin and saquinavir are substrates and inhibitors of CYP3A and there is evidence of a bi-directional drug interaction (see Saquinavir under “Drugs That Affect Clarithromycin Tablets” in the table below) [see Pharmacokinetics ] .
Ritonavir Etravirine		Ritonavir, Etravirine: (see Ritonavir and Etravirine under “Drugs That Affect Clarithromycin Tablets” in the table below) [see Pharmacokinetics ] .
Maraviroc		Maraviroc: Clarithromycin may result in increases in maraviroc exposures by inhibition of CYP3A metabolism. See maraviroc prescribing information for dose recommendation when given with strong CYP3A inhibitors such as clarithromycin.
Boceprevir (in patients with normal renal function) Didanosine	No Dose Adjustment	Boceprevir: Both clarithromycin and boceprevir are substrates and inhibitors of CYP3A, potentially leading to a bi-directional drug interaction when co‑administered. No dose adjustments are necessary for patients with normal renal function (see boceprevir prescribing information).
Zidovudine		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 [see Pharmacokinetics ] . The impact of co-administration of clarithromycin extended-release tablets or granules and zidovudine has not been evaluated.
Calcium Channel Blockers:
Verapamil	Use With Caution	Verapamil: Hypotension, bradyarrhythmias, and lactic acidosis have been observed in patients receiving concurrent verapamil, [see Warnings and Precautions ] .
Amlodipine Diltiazem		Amlodipine, Diltiazem: [See Warnings and Precautions ]
Nifedipine		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 [see Warnings and Precautions ] .
Ergot Alkaloids:
Ergotamine Dihydroergotamine	Contraindicated	Ergotamine, Dihydroergotamine: Postmarketing reports indicate that coadministration of clarithromycin with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system [see Contraindications ] .
Gastroprokinetic Agents:
Cisapride	Contraindicated	Cisapride: [See Contraindications ]
Lipid-lowering agents: Lomitapide
Lovastatin Simvastatin	Contraindicated	Lomitapide, Lovastatin, Simvastatin: Clarithromycin may increase the exposure of these drugs by inhibition of CYP3A metabolism, thereby increasing the risk of toxicities from these drugs [see Contraindications and Warnings and Precautions ] Atorvastatin, Pravastatin, Fluvastatin: [See Warnings and Precautions ]
Atorvastatin Pravastatin	Use With Caution
Fluvastatin	No Dose Adjustment
Hypoglycemic Agents:
Nateglinide Pioglitazone Repaglinide Rosiglitazone	Use With Caution	Nateglinide, Pioglitazone, Repaglinide, Rosiglitazone: [See Warnings and Precautions and Adverse Reactions ]
Insulin		Insulin: [See Warnings and Precautions and Adverse Reactions ]
Immunosuppressants:
Cyclosporine	Use With Caution	Cyclosporine: There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with cyclosporine.
Tacrolimus		Tacrolimus: There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with tacrolimus.
Phosphodiesterase inhibitors:
Sildenafil Tadalafil Vardenafil	Use With Caution	Sildenafil, Tadalafil, Vardenafil: Each of these phosphodiesterase inhibitors is primarily metabolized by CYP3A, and CYP3A will be inhibited by concomitant administration of clarithromycin. Co-administration of clarithromycin with sildenafil, tadalafil, or vardenafil will result in increased exposure of these phosphodiesterase inhibitors. Co-administration of these phosphodiesterase inhibitors with clarithromycin is not recommended. Increased systemic exposure of these drugs may occur with clarithromycin; reduction of dosage for phosphodiesterase inhibitors should be considered (see their respective prescribing information).
Proton Pump Inhibitors:
Omeprazole	No Dose Adjustment	Omeprazole: The mean 24-hour gastric pH value was 5.2 when omeprazole was administered alone and 5.7 when coadministered with clarithromycin as a result of increased omeprazole exposures [see Pharmacokinetics ] (see also Omeprazole under “Drugs That Affect Clarithromycin Tablets” in the table below).
Xanthine Derivatives:
Theophylline	Use With Caution	Theophylline: Clarithromycin use in patients who are receiving theophylline may be associated with an increase of serum theophylline concentrations [see Pharmacokinetics ] . Monitoring of serum theophylline concentrations should be considered for patients receiving high doses of theophylline or with baseline concentrations in the upper therapeutic range.
Triazolobenzodiazepines and Other Related Benzodiazepines:
Midazolam	Use With Caution	Midazolam: When oral midazolam is co‑administered with clarithromycin, dose adjustments may be necessary and possible prolongation and intensity of effect should be anticipated [see Warnings and Precautions and Pharmacokinetics ] .
Alprazolam Triazolam		Triazolam, Alprazolam: Caution and 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 (e.g., somnolence and confusion) with the concomitant use of clarithromycin and triazolam. Monitoring the patient for increased CNS pharmacological effects is suggested. In postmarketing experience, erythromycin has been reported to decrease the clearance of triazolam and midazolam, and thus, may increase the pharmacologic effect of these benzodiazepines.
Temazepam Nitrazepam Lorazepam	No Dose Adjustment	Temazepam, Nitrazepam, Lorazepam: For benzodiazepines which are not metabolized by CYP3A (e.g., temazepam, nitrazepam, lorazepam), a clinically important interaction with clarithromycin is unlikely.
Cytochrome P450 Inducers:
Rifabutin	Use With Caution	Rifabutin: 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 (see Rifabutin under “Drugs That Affect Clarithromycin Tablets” in the table below).
Other Drugs Metabolized by CYP3A:
Alfentanil Bromocriptine Cilostazol Methylprednisolone Vinblastine Phenobarbital St. John’s Wort	Use With Caution	There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with alfentanil, methylprednisolone, cilostazol, bromocriptine, vinblastine, phenobarbital, and St. John’s Wort.
Other Drugs Metabolized by CYP450 Isoforms Other than CYP3A:
Hexobarbital Phenytoin Valproate	Use With Caution	There have been postmarketing reports of interactions of clarithromycin with drugs not thought to be metabolized by CYP3A, including hexobarbital, phenytoin, and valproate.
Drugs that Affect Clarithromycin Tablets
Drug(s) that Affect the Pharmacokinetics of Clarithromycin Tablets	Recommendation	Comments
Antifungals:
Itraconazole	Use With Caution	Itraconazole: 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 (see also Itraconazole under “Drugs That Are Affected By Clarithromycin Tablets” in the table above).
Antivirals:
Atazanavir	Use With Caution	Atazanavir: When clarithromycin is co-administered with atazanavir, the dose of clarithromycin should be decreased by 50% [see Clinical Pharmacology ] . Since concentrations of 14-OH clarithromycin are significantly reduced when clarithromycin is co‑administered with atazanavir, alternative antibacterial therapy should be considered for indications other than infections due to Mycobacterium avium complex. Doses of clarithromycin greater than 1000 mg per day should not be co-administered with protease inhibitors.
Ritonavir (in patients with decreased renal function)		Ritonavir: 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 [see Pharmacokinetics ] . Doses of clarithromycin greater than 1000 mg per day should not be co-administered with protease inhibitors.
Saquinavir (in patients with decreased renal function)		Saquinavir: When saquinavir is co-administered with ritonavir, consideration should be given to the potential effects of ritonavir on clarithromycin (refer to ritonavir above) [see Pharmacokinetics ] .
Etravirine		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.
Saquinavir (in patients with normal renal function) Ritonavir (in patients with normal renal function)	No Dose Adjustment
Proton Pump Inhibitors:
Omeprazole	Use With Caution	Omeprazole: Clarithromycin concentrations in the gastric tissue and mucus were also increased by concomitant administration of omeprazole [see Pharmacokinetics ] .
Miscellaneous Cytochrome P450 Inducers:
Efavirenz Nevirapine Rifampicin Rifabutin Rifapentine	Use With Caution	Inducers of CYP3A enzymes, such as efavirenz, nevirapine, rifampicin, rifabutin, and rifapentine will increase the metabolism of clarithromycin, thus decreasing plasma concentrations of clarithromycin, while increasing those of 14-OH-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. Alternative antibacterial treatment should be considered when treating patients receiving inducers of CYP3A. There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with rifabutin (see Rifabutin under “Drugs That Are Affected By Clarithromycin Tablets” in the table above).

Co-administration of clarithromycin tablets can alter the concentrations of other drugs. The potential for drug-drug interactions must be considered prior to and during therapy.

)

05/2023

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 Bacterial Exacerbation of Chronic Bronchitis
Clarithromycin tablets are 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 ]
.
)
•Acute Maxillary Sinusitis (
1.2 Acute Maxillary Sinusitis
Clarithromycin tablets are 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 ]
.
)
•Community-Acquired Pneumonia (
1.3 Community-Acquired Pneumonia
Clarithromycin tablets are indicated
[see Indications and Usage ]
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)
)
•Pharyngitis/Tonsillitis (
1.4 Pharyngitis/Tonsillitis
Clarithromycin tablets are 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.
)
•Uncomplicated Skin and Skin Structure Infections (
1.5 Uncomplicated Skin and Skin Structure Infections
Clarithromycin tablets are indicated for the treatment of mild to moderate infections caused by susceptible isolates due to
Staphylococcus aureus
, or
S
treptococcus pyogenes
.
)
•Acute Otitis Media in Pediatric Patients (
1.6 Acute Otitis Media
Clarithromycin tablets are 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 ]
.
)
•Treatment and Prophylaxis of Disseminated Mycobacterial Infections (
1.7 Treatment and Prophylaxis of Disseminated Mycobacterial Infections
Clarithromycin tablets are indicated for the treatment of mild to moderate infections caused by susceptible isolates due to
Mycobacterium avium
or
Myc
obacterium intracellulare
in patients with advanced HIV infection
[see Clinical Studies (
14.1
)]
.
)
•
Helicobacter pylori
Infection and Duodenal Ulcer Disease in Adults (
1.8
Helicobacter pylori
Infection and Duodenal Ulcer Disease
Clarithromycin tablets are given in combination with other drugs in adults as described below to eradicate
H. pylori
. The eradication of
H. pylori
has been demonstrated to reduce the risk of duodenal ulcer recurrence
[see Clinical Studies (
14.3
)]
.
- •Clarithromycin tablets in combination with amoxicillin and PREVACID (lansoprazole) or PRILOSEC (omeprazole) delayed-release capsules, as triple therapy, are indicated for the treatment of patients with
  H. pylori
  infection and duodenal ulcer disease (active or five-year history of duodenal ulcer) to eradicate
  H. pylori
  .
- •Clarithromycin tablets in combination with PRILOSEC (omeprazole) capsules are indicated for the treatment of patients with an active duodenal ulcer associated with
  H. pylori
  infection. Regimens which contain clarithromycin tablets as the single antibacterial agent are more likely to be associated with the development of clarithromycin resistance among patients who fail therapy. Clarithromycin-containing regimens should not be used in patients with known or suspected clarithromycin resistant isolates because the efficacy of treatment is reduced in this setting.
)

Limitations of Use

To reduce the development of drug-resistant bacteria and maintain the effectiveness of clarithromycin tablets and other antibacterial drugs, clarithromycin tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. (

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.

)

•

Adults

: clarithromycin tablets 250 mg or 500 mg every 12 hours for 7 to 14 days (

2.2 Adult Dosage

The recommended dosages of clarithromycin tablets for the treatment of mild to moderate infections in adults are listed in

Table 1

Table 1. Adult Dosage Guidelines
Infection	Clarithromycin Tablets
Infection	Dosage (every 12 hours)	Duration (days)
Acute bacterial exacerbation of chronic bronchitis	250 to 500 mg	7^†-14
Acute maxillary sinusitis	500 mg	14
Community-acquired pneumonia	250 mg	7^ǂ-14
Pharyngitis/Tonsillitis	250 mg	10
Uncomplicated skin and skin structure infections	250 mg	7-14
Treatment and prophylaxis of disseminated Mycobacterium avium disease [see Dosage and Administration ( 2.5 )]	500 mg^§	-
H.pylori eradication to reduce the risk of duodenal ulcer recurrence with amoxicillin and omeprazole or lansoprazole [see Dosage and Administration ( 2.3 )]	500 mg	10-14
H.pylori eradication to reduce the risk of duodenal ulcer recurrence with omeprazole [see Dosage and Administration ]	500 mg every 8 hours	14

^*For

M. catarrhalis

and

S. pneumoniae

use 250 mg. For

H. influenzae

and

H. parainfluenzae

, use 500 mg.

^†For

H parainfluenzae

, the duration of therapy is 7 days.

^ǂFor

H. influenzae

, the duration of therapy is 7 days.

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

)

•
H. pylori
eradication (in combination with lansoprazole/amoxicillin, omeprazole/amoxicillin, or omeprazole): clarithromycin tablets 500 mg every 8 or 12 hours for 10 to 14 days. See full prescribing information (FPI) for additional information. (
2.3 Combination Dosing Regimens for
H. pylori
Infection
- •
  Triple therapy: clarithromycin/lansoprazole/amoxicillin
  
  The recommended adult dosage is 500 mg clarithromycin tablets, 30 mg lansoprazole, and 1 gram amoxicillin, all given every 12 hours for 10 or 14 days
  [see Indications and Usage and Clinical Studies ]
  .
- •
  Triple therapy: clarithromycin/omeprazole/amoxicillin
  
  The recommended adult dosage is 500 mg clarithromycin tablets, 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
  [see Indications and Usage and Clinical Studies ]
  .
- •
  Dual therapy: clarithromycin/omeprazole
  
  The recommended adult dosage is 500 mg clarithromycin tablets 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
  [see Indications and Usage and Clinical Studies ]
  .
)
•
Pediatric Patients
: clarithromycin 15 mg/kg/day divided every 12 hours for 10 days (
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 ]
.
)
•
Mycobacterial Infections
: clarithromycin tablets 500 mg every 12 hours; clarithromycin tablets 7.5 mg/kg up to 500 mg every 12 hours in pediatric patients (
2.5 Dosage Regimens for Mycobacterial Infections
For the treatment of disseminated infection due to
Mycobacterium avium
complex (MAC), clarithromycin tablets are recommended as the primary agents. Clarithromycin tablets 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 ].
Adult Patients
For treatment and prophylaxis of mycobacterial infections in adults, the recommended dose of clarithromycin tablets 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 and Clinical Studies ]
.
Clarithromycin tablets therapy should continue if clinical response is observed. Clarithromycin tablets can be discontinued when the patient is considered at low risk of disseminated infection.
)

•Reduce dose in moderate renal impairment with concomitant atazanavir or ritonavir-containing regimens and in severe renal impairment (

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 ].

Table 2. Clarithromycin Tablets Dosage Adjustments in Patients with Renal Impairment
	Recommended Clarithromycin Tablets Dosage Reduction
Patients with severe renal impairment (CL_crof <30 mL/min)	Reduce the dosage of clarithromycin tablets by 50%
Patients with moderate renal impairment (CL_crof 30 to 60 mL/min) taking concomitant atazanavir or ritonavir-containing regimens	Reduce the dosage of clarithromycin tablets by 50%
Patients with severe renal impairment (CL_crof <30 mL/min) taking concomitant atazanavir or ritonavir-containing regimens	Reduce the dosage of clarithromycin tablets by 75%

)

Geriatric

: Increased risk of

torsades de pointes

(

8.5 Geriatric Use

In a steady-state study in which healthy elderly subjects (65 years to 81 years of age) were given 500 mg of clarithromycin tablets every 12 hours, the maximum serum concentrations and area under the curves of clarithromycin and 14-OH clarithromycin were increased compared to those achieved in healthy young adults. These changes in pharmacokinetics parallel known age-related decreases in renal function. 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

[see Warnings and Precautions ]

Most reports of acute kidney injury with calcium channel blockers metabolized by CYP3A4 (e.g., verapamil, amlodipine, diltiazem, nifedipine) involved elderly patients 65 years of age or older

[see Warnings and Precautions ]

Especially in elderly patients, there have been reports of colchicine toxicity with concomitant use of clarithromycin and colchicine, some of which occurred in patients with renal insufficiency. Deaths have been reported in some patients

[see Contraindications and Warnings and Precautions ]

)

•Hypersensitivity to clarithromycin or any macrolide drug (
4.1 Hypersensitivity
Clarithromycin tablets are contraindicated in patients with a known hypersensitivity to clarithromycin, erythromycin, or any of the macrolide antibacterial drugs
[see Warnings and Precautions ]
.
)
•Cisapride and pimozide (
4.2 Cisapride and Pimozide
Concomitant administration of clarithromycin tablets with cisapride and pimozide is contraindicated
[see Drug Interactions ]
.
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 tablets. Fatalities have been reported.
)
•History of cholestatic jaundice/hepatic dysfunction with use of clarithromycin (
4.3 Cholestatic Jaundice/Hepatic Dysfunction
Clarithromycin tablets are contraindicated in patients with a history of cholestatic jaundice or hepatic dysfunction associated with prior use of clarithromycin.
)
•Colchicine in renal or hepatic impairment (
4.4 Colchicine
Concomitant administration of clarithromycin tablets and colchicine is contraindicated in patients with renal or hepatic impairment.
)
•Lomitapide, lovastatin, and simvastatin
•Ergot alkaloids (ergotamine or dihydroergotamine) (
4.6 Ergot Alkaloids
Concomitant administration of clarithromycin and ergotamine or dihydroergotamine is contraindicated
[see Drug Interactions ]
.
)
•Lurasidone (
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
].
)

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