Gastroprokinetic Agents: Cisapride Contraindicated Cisapride: [See Contraindications ( 4.2 )] 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 ( 4.5 ) and Warnings and Precautions ( 5.4 )] Atorvastatin, Pravastatin, Fluvastatin: [See Warnings and Precautions ( 5.4 )] 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 ( 5.4 ) and Adverse Reactions ( 6.2 )] Insulin Insulin: [See Warnings and Precautions ( 5.4 ) and Adverse Reactions ( 6.2 )] Immunosuppressants: Cyclosporine Use With Caution Cyclosporine: There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with cyclosporine.
Source: FDA drug label - clarithromycin
Combination Therapy with Clarithromycin and Amoxicillin Clinical Impact: Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions, including potentially fatal arrhythmias, and are contraindicated. Intervention: See Contraindications, Warnings and Precautions in prescribing information for clarithromycin.
Source: FDA drug label - esomeprazole magnesium
] Ezetimibe and Simvastatin Tablets Drug Interactions Associated With Increased Risk of Myopathy/Rhabdomyolysis ( 2.3 , 2.4 , 4 , 5.1 , 7.1 , 7.2 , 7.3 , 7.8 , 12.3 ) Interacting Agents Prescribing Recommendations Strong CYP3A4 Inhibitors, (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, cobicistat-containing products), gemfibrozil, cyclosporine, danazol Contraindicated with ezetimibe and simvastatin tablets Niacin (≥1 g/day) For Chinese patients, not recommended with ezetimibe and simvastatin tablets Verapamil, diltiazem, dronedarone Do not exceed 10 mg/10 mg ezetimibe and simvastatin tablets, daily Amiodarone, amlodipine, ranolazine Do not exceed 10 mg/20 mg ezetimibe and simvastatin tablets, daily Lomitapide For patients with HoFH, do not exceed 10 mg/20 mg ezetimibe and simvastatin tablets 1 Daptomycin Temporally suspend ezetimibe and simvastatin tablets Grapefruit juice Avoid grapefruit juice 1. If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with ezetimibe and simvastatin tablets must be suspended during the course of treatment.
Source: FDA drug label - ezetimibe and simvastatin
Fluconazole No Dose Adjustment Fluconazole: [see Pharmacokinetics ( 12.3 )] 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).
Source: FDA drug label - clarithromycin
Gastroprokinetic Agents: Cisapride Contraindicated Cisapride: [See Contraindications ( 4.2 )] 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 ( 4.5 ) and Warnings and Precautions ( 5.4 )] Atorvastatin, Pravastatin, Fluvastatin: [See Warnings and Precautions ( 5.4 )] 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 ( 5.4 ) and Adverse Reactions ( 6.2 )] Insulin Insulin: [See Warnings and Precautions ( 5.4 ) and Adverse Reactions ( 6.2 )] Immunosuppressants: Cyclosporine Use With Caution Cyclosporine: There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with cyclosporine.
Source: FDA drug label - clarithromycin
Gastroprokinetic Agents: Cisapride Contraindicated Cisapride: [See Contraindications ( 4.2 )] 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 ( 4.5 ) and Warnings and Precautions ( 5.4 )] Atorvastatin, Pravastatin, Fluvastatin: [See Warnings and Precautions ( 5.4 )] 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 ( 5.4 ) and Adverse Reactions ( 6.2 )] Insulin Insulin: [See Warnings and Precautions ( 5.4 ) and Adverse Reactions ( 6.2 )] Immunosuppressants: Cyclosporine Use With Caution Cyclosporine: There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with cyclosporine.
Source: FDA drug label - clarithromycin
Combination Therapy with Clarithromycin and Amoxicillin Clinical Impact: Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions, including potentially fatal arrhythmias, and are contraindicated. Intervention: See Contraindications and Warnings and Precautions in prescribing information for clarithromycin.
Source: FDA drug label - rabeprazole sodium
( 7.2 ) 7.1 Effects of Other Drugs on Ranolazine Strong CYP3A Inhibitors Do not use ranolazine with strong CYP3A inhibitors, including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir [see Contraindications (4) , Clinical Pharmacology (12.3) ].
Source: FDA drug label - ranolazine
In vivo studies Do not use vardenafil orally disintegrating tablet with moderate and strong CYP3A4 inhibitors such as erythromycin, grapefruit juice, clarithromycin, ketoconazole, itraconazole, indinavir, saquinavir, atazanavir, ritonavir as the systemic concentration of vardenafil is increased in their presence [see Warnings and Precautions (5) and Dosage and Administration ( 2.4 )] .
Source: FDA drug label - vardenafil
Cases of life-threatening interactions have been reported for disopyramide when given with clarithromycin and erythromycin indicating that coadministration of disopyramide with inhibitors of cytochrome P450 3A4 could result in potentially fatal interaction.
Source: FDA drug label - disopyramide phosphate
Intervention Avoid concomitant use of FOCINVEZ Examples Moderate inhibitor: diltiazem Strong inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir Strong CYP3A4 Inducers Clinical Impact Substantially decreased exposure of aprepitant in patients chronically taking a strong CYP3A4 inducer may decrease the efficacy of FOCINVEZ [see Clinical Pharmacology (12.3)] .
Source: FDA drug label - fosaprepitant dimeglumine
7.2 Strong Inducers and Strong Inhibitors of CYP3A4 and P-gp Avoid concomitant use of sirolimus with strong inducers (e.g., rifampin, rifabutin) and strong inhibitors (e.g., ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, clarithromycin) of CYP3A4 and P-gp.
Source: FDA drug label - sirolimus
Increase tacrolimus dose and monitor tacrolimus whole blood trough concentrations [see Dosage and Administration ( 2.2 , 2.6 ) and Clinical Pharmacology (12.3 ) ] Strong CYP3A Inhibitors : Protease inhibitors (e.g, nelfinavir, telaprevir, boceprevir, ritonavir), azole antifungals (e.g., voriconazole, posaconazole, itraconazole, ketoconazole), antibiotics (e.g., clarithromycin, troleandomycin, chloramphenicol), nefazodone,letermovir, Schisandra sphenanthera extracts May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation).A rapid, sharp rise in tacrolimus levels may occur early, despite an immediate reduction of tacrolimus dose [see Warnings and Precautions ( 5.6 , 5.11 , 5.12 )] Reduce tacrolimus dose (for voriconazole and posaconazole, give one-third of the original dose) and adjust dose based on tacrolimus whole blood trough concentrations [see Dosage and Administration ( 2.2 , 2.6 ) and Clinical Phamacology ( 12.3 )].
Source: FDA drug label - tacrolimus
Strong CYP3A Inhibitors : Protease inhibitors (e.g., nelfinavir, telaprevir, boceprevir, ritonavir), azole antifungals (e.g., voriconazole, posaconazole, itraconazole, ketoconazole), antibiotics (e.g., clarithromycin, troleandomycin, chloramphenicol), nefazodone, letermovir, Schisandra sphenanthera extracts May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation).
Source: FDA drug label - tacrolimus extended-release capsules
( 7.1 ) 7.1 Effect of Other Drugs on TALZENNA Effect of P-gp Inhibitors Breast Cancer Avoid coadministration of TALZENNA with the following P-gp inhibitors: itraconazole, amiodarone, carvedilol, clarithromycin, itraconazole, and verapamil.
Source: FDA drug label - talazoparib
Avoid use of strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir and telithromycin) [see Clinical Pharmacology ( 12.3 )] .
Source: FDA drug label - ticagrelor
Examples Ketoconazole, itraconazole, clarithromycin Moderate or Weak Inhibitors of CYP3A Clinical implication Concomitant use of alprazolam with CYP3A inhibitors may increase the concentrations of alprazolam, resulting in increased risk of adverse reactions of alprazolam [see Clinical Pharmacology (12.3) ].
Source: FDA drug label - alprazolam
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 ( 12.3 )] . 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 ( 12.3 )] . 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 ( 12.3 )] .
Source: FDA drug label - clarithromycin
Caution should be exercised when considering the co-administration of PULMICORT FLEXHALER with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Warnings and Precautions (5.7) ] .
Source: FDA drug label - budesonide
Caution should be exercised when considering the coadministration of budesonide and formoterol fumarate dihydrate with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Warnings and Precautions (5.9) ] .
Source: FDA drug label - budesonide and formoterol fumarate dihydrate
Co-administration of deflazacort with clarithromycin, a strong CYP3A4 inhibitor, increased total exposure to 21-desDFZ by about 3-fold. Therefore, give one third the recommended dosage of deflazacort when moderate or strong CYP3A4 inhibitors (e.g., clarithromycin, fluconazole, diltiazem, verapamil, grapefruit juice) are used concomitantly with deflazacort [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ] .
Source: FDA drug label - deflazacort
Concomitant administration of moderate or strong CYP3A4 inhibitors such as azole antifungals (e.g., ketoconazole, itraconazole, voriconazole, fluconazole), verapamil, macrolides (e.g., clarithromycin, erythromycin), diltiazem, and grapefruit juice can increase the plasma concentrations of the estrogen or the progestin or both.
Source: FDA drug label - drospirenone and ethinyl estradiol
[See Clinical Pharmacology (12.3).] Substances Increasing the Systemic Exposure of COCs (enzyme inhibitors): Concomitant administration of moderate or strong CYP3A4 inhibitors like azole antifungals (for example, ketoconazole, itraconazole, voriconazole, fluconazole), verapamil, macrolides (for example, clarithromycin, erythromycin), diltiazem, and grapefruit increase the serum concentrations of both estradiol and dienogest.
Source: FDA drug label - estradiol valerate and estradiol valerate/dienogest
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.
Source: FDA drug label - clarithromycin
Examples: Ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil Moderate CYP3A4 Inhibitors Clinical Impact: Concomitant use of lurasidone hydrochloride with moderate CYP3A4 inhibitors increased the exposure of lurasidone compared to the use of lurasidone hydrochloride alone [see Clinical Pharmacology ( 12.3 )].
Source: FDA drug label - lurasidone hydrochloride
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.
Source: FDA drug label - clarithromycin
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 ( 5.4 ) and Pharmacokinetics ( 12.3 )] . 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.
Source: FDA drug label - clarithromycin
Caution should be exercised when considering the coadministration of ASMANEX HFA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, cobicistat-containing products, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Warnings and Precautions (5.6) and Clinical Pharmacology (12.3) ] .
Source: FDA drug label - mometasone furoate
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 ( 12.3 )] (see also Omeprazole under “Drugs That Affect Clarithromycin Tablets” in the table below). 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 ( 12.3 )] .
Source: FDA drug label - omeprazole
Caution should be exercised when paclitaxel is concomitantly administered with known substrates (e.g., midazolam, buspirone, felodipine, lovastatin, eletriptan, sildenafil, simvastatin, and triazolam), inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin), and inducers (e.g., rifampin and carbamazepine) of CYP3A4.
Source: FDA drug label - paclitaxel
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. 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.
Source: FDA drug label - clarithromycin
Clarithromycin (a component of VOQUEZNA TRIPLE PAK) is a strong CYP3A inhibitor. Table 4: Effects of Other Drugs on VOQUEZNA TRIPLE PAK Strong or Moderate CYP3A Inducers Clinical Effect Vonoprazan and clarithromycin are CYP3A substrates. Strong or moderate CYP3A inducers may decrease exposure of vonoprazan and clarithromycin [see Clinical Pharmacology (12.3) ] , which may reduce the effectiveness of VOQUEZNA TRIPLE PAK.
Source: FDA drug label - vonoprazan fumarate
Amlodipine Diltiazem Amlodipine, Diltiazem: [See Warnings and Precautions ( 5.4 )] Nifedipine Nifedipine: Nifedipine is a substrate for CYP3A.
Source: FDA drug label - clarithromycin
Intervention: In patients taking clarithromycin or itraconazole, do not exceed atorvastatin 20 mg [see Dosage and Administration ( 2 )] . Examples: Erythromycin, clarithromycin, itraconazole, ketoconazole, posaconazole, and voriconazole.
Source: FDA drug label - amlodipine and atorvastatin
However, strong inhibitors of CYP3A (e.g., itraconazole, clarithromycin) may increase the plasma concentrations of amlodipine to a greater extent [see Drug Interactions (7.1) ] .
Source: FDA drug label - amlodipine besylate
Clarithromycin Although clarithromycin is a combined P-gp and strong CYP3A4 inhibitor, pharmacokinetic data suggest that no dose adjustment is necessary with concomitant administration with apixaban [see Clinical Pharmacology ( 12.3) ].
Source: FDA drug label - apixaban
7 DRUG INTERACTIONS Dosage adjustment due to drug interactions (7.1): Factors Dosage Adjustments for Aripiprazole Known CYP2D6 Poor Metabolizers Administer half of usual dose Known CYP2D6 Poor Metabolizers and strong CYP3A4 inhibitors Administer a quarter of usual dose Strong CYP2D6 or CYP3A4 inhibitors Administer half of usual dose Strong CYP2D6 and CYP3A4 inhibitors Administer a quarter of usual dose Strong CYP3A4 inducers Double usual dose over 1 to 2 weeks 7.1 Drugs Having Clinically Important Interactions with Aripiprazole Table 25: Clinically Important Drug Interactions with Aripiprazole: Concomitant Drug Name or Drug Class Clinical Rationale Clinical Recommendation Strong CYP3A4 Inhibitors (e.g., itraconazole, clarithromycin) or strong CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine) The concomitant use of aripiprazole with strong CYP 3A4 or CYP2D6 inhibitors increased the exposure of aripiprazole compared to the use of aripiprazole alone [see Clinical Pharmacology (12.3)].
Source: FDA drug label - aripiprazole
Examples: itraconazole, clarithromycin, quinidine, fluoxetine, paroxetine Strong CYP3A4 Inducers Clinical Impact: The concomitant use of oral aripiprazole and carbamazepine decreased the exposure of aripiprazole compared to the use of oral aripiprazole alone [see Clinical Pharmacology ( 12.3 )].
Source: FDA drug label - aripiprazole lauroxil
Macrolide antibiotics: clarithromycin ↑ clarithromycin ↓ 14-OH clarithromycin ↑ atazanavir Increased concentrations of clarithromycin may cause QTc prolongations; therefore, a dose reduction of clarithromycin by 50% should be considered when it is coadministered with REYATAZ. In addition, concentrations of the active metabolite 14-OH clarithromycin are significantly reduced; consider alternative therapy for indications other than infections due to Mycobacterium avium complex. Coadministration of REYATAZ with ritonavir and clarithromycin has not been studied.
Source: FDA drug label - atazanavir
Intervention: In patients taking clarithromycin or itraconazole, do not exceed atorvastatin 20 mg [see Dosage and Administration (2.5) ]. Examples: Erythromycin, clarithromycin, itraconazole, ketoconazole, posaconazole, and voriconazole.
Source: FDA drug label - atorvastatin calcium
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).
Source: FDA drug label - clarithromycin
( 7.1 ) 7.1 Effect of Other Drugs on TEMBEXA Inhibitors for Organic Anion Transporting Polypeptide (OATP) 1B1 and 1B3 Concomitant use of TEMBEXA with OATP1B1 and 1B3 inhibitors (clarithromycin, cyclosporine, erythromycin, gemfibrozil, human immunodeficiency virus [HIV] and hepatitis C virus [HCV] protease inhibitors, rifampin [single dose]) increase brincidofovir AUC and C max which may increase TEMBEXA-associated adverse reactions [see Clinical Pharmacology ( 12.3 )] .
Source: FDA drug label - brincidofovir
Antimycobacterials: Rifampin a Rifapentine ↓Cabotegravir ↓Rilpivirine Antimycobacterial: Rifabutin a ↓Cabotegravir ↔Rifabutin ↓Rilpivirine Glucocorticoid (systemic): Dexamethasone (more than a single-dose treatment) ↓Rilpivirine Herbal product: St John’s wort ( Hypericum perforatum ) ↓Rilpivirine Macrolide or ketolide antibiotics: Azithromycin Clarithromycin Erythromycin ↔Cabotegravir ↑Rilpivirine Macrolides are expected to increase concentrations of rilpivirine and are associated with a risk of Torsade de Pointes [see Warnings and Precautions ( 5.5 )] .
Source: FDA drug label - cabotegravir and rilpivirine
Drugs that have been shown, or would be expected, to increase plasma carbamazepine levels include aprepitant, cimetidine, ciprofloxacin, danazol, diltiazem, macrolides (e.g., erythromycin, clarithromycin), fluoxetine, fluvoxamine, trazodone, omeprazole, oxybutynin, isoniazid, niacinamide (nicotinamide), azoles (e.g., ketaconazole, itraconazole, fluconazole, voriconazole), acetazolamide, verapamil, ticlopidine, grapefruit juice, and protease inhibitors.
Source: FDA drug label - carbamazepine
Other Lipid-Lowering Drugs: fibrates, gemfibrozil Digitalis Glycosides: digoxin P-gp substrate; rhabdomyolysis has been reported Coadministration of P-gp and/or CYP3A4 inhibitors (e.g., clarithromycin or cyclosporine) have been demonstrated to alter the concentration of colchicine. Drug Interactions: Pharmacokinetic Parameters for Colchicine Tablets in the Presence of the Coadministered Drug Coadministered Drug Dose of Coadministered Drug (mg) Dose of Colchicine Tablets (mg) N % Change in Colchicine Concentrations from Baseline (Range: Min – Max) C max AUC 0-t Cyclosporine 100 mg single dose 0.6 mg single dose 23 270.0 (62.0 to 606.9) 259.0 (75.8 to 511.9) Clarithromycin 250 mg twice daily, 7 days 0.6 mg single dose 23 227.2 (65.7 to 591.1) 281.5 (88.7 to 851.6) Ketoconazole 200 mg twice daily, 5 days 0.6 mg single dose 24 101.7 (19.6 to 219.0) 212.2 (76.7 to 419.6) Ritonavir 100 mg twice daily, 5 days 0.6 mg single dose 18 184.4 (79.2 to 447.4) 296.0 (53.8 to 924.4) Verapamil 240 mg daily, 5 days 0.6 mg single dose 24 40.1 (-47.1 to 149.5) 103.3 (-9.8 to 217.2) Diltiazem 240 mg daily, 7 days 0.6 mg single dose 20 44.2 (-46.0 to 318.3) 93.4 (-30.2 to 338.6) Azithromycin 500 mg x 1 day, then 250 mg x 4 days 0.6 mg single dose 21 21.6 (-41.7 to 222.0) 57.1 (-24.3 to 241.1) Grapefruit juice 240 mL twice daily, 4 days 0.6 mg single dose 21 -2.55 (-53.4 to 55.0) -2.36 (-46.4 to 62.2) Estrogen-containing oral contraceptives: In healthy female volunteers given ethinyl estradiol and norethindrone (Ortho-Novum ® 1/35) coadministered with colchicine tablets (0.6 mg twice daily × 14 days), hormone concentrations are not affected.
Source: FDA drug label - colchicine
Drugs That Increase Cyclosporine Concentrations Calcium Channel Blockers Antifungals Antibiotics Glucocorticoids Other Drugs diltiazem fluconazole azithromycin methylprednisolone Allopurinol nicardipine itraconazole clarithromycin Amiodarone verapamil ketoconazole erythromycin Bromocriptine voriconazole quinupristin/ dalfopristin colchicine danazol imatinib metoclopramide nefazodone oral contraceptives HIV Protease inhibitors The HIV protease inhibitors (e.g., indinavir, nelfinavir, ritonavir, and saquinavir) are known to inhibit cytochrome P-450 3A and thus could potentially increase the concentrations of cyclosporine, however no formal studies of the interaction are available.
Source: FDA drug label - cyclosporine
The use of the P-gp inhibitors verapamil, amiodarone, quinidine, clarithromycin, and ticagrelor does not require a dosage adjustment of dabigatran etexilate.
Source: FDA drug label - dabigatran etexilate
Antibacterial: clarithromycin ↔ darunavir ↑ clarithromycin No dose adjustment of the combination is required for patients with normal renal function. For co-administration of clarithromycin and darunavir/ritonavir in patients with renal impairment, the following dose adjustments should be considered: For subjects with CLcr of 30 mL/min to 60 mL/min, the dose of clarithromycin should be reduced by 50%. For subjects with CLcr of < 30 mL/min, the dose of clarithromycin should be reduced by 75%.
Source: FDA drug label - darunavir
Antibacterials: clarithromycin, erythromycin, telithromycin ↑ darunavir ↑ cobicistat ↑ antibacterial Consider alternative antibiotics with concomitant use of PREZCOBIX.
Source: FDA drug label - darunavir ethanolate and cobicistat
Co-administration with other drugs which strongly inhibit CYP 3A4 (e.g., itraconazole, clarithromycin, ritonavir, cobicistat-containing products) may lead to increased plasma concentrations of corticosteroids and potentially increase the risk for systemic corticosteroid side effects.
Source: FDA drug label - dexamethasone
Captopril 58% 39% Clarithromycin NA 70% Dronedarone NA 150% Gentamicin 129-212% NA Erythromycin 100% NA Itraconazole 80% NA Lapatinib NA 180% Propafenone NA 60-270% Quinidine 100% NA Ranolazine 50% NA Ritonavir NA 86% Telaprevir 50% 85% Tetracycline 100% NA Verapamil 50-75% NA Digoxin concentrations increased less than 50% Atorvastatin 22% 15% Carvedilol 16% 14% Measure serum digoxin concentrations before initiating concomitant drugs.
Source: FDA drug label - digoxin
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. 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.
Source: FDA drug label - clarithromycin
Anti-infective: Clarithromycin ↓ clarithromycin * ↑ 14-OH metabolite * Consider alternatives to macrolide antibiotics because of the risk of QT interval prolongation.
Source: FDA drug label - efavirenz
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.
Source: FDA drug label - clarithromycin
Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and grapefruit juice may increase plasma concentrations of estrogens and may result in adverse reactions.
Source: FDA drug label - estradiol
Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and may result in adverse reactions.
Source: FDA drug label - estradiol and levonorgestrel
Other strong inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, nefazodone, troleandomycin, ritonavir, nelfinavir) would be expected to behave similarly.
Source: FDA drug label - eszopiclone
Antiinfective : clarithromycin ↑ etravirine ↓ clarithromycin ↑ 14-OH- clarithromycin Clarithromycin exposure was decreased by etravirine tablets; however, concentrations of the active metabolite, 14- hydroxy-clarithromycin, were increased. Because 14-hydroxy-clarithromycin has reduced activity against Mycobacterium avium complex (MAC), overall activity against this pathogen may be altered. Alternatives to clarithromycin, such as azithromycin, should be considered for the treatment of MAC.
Source: FDA drug label - etravirine
The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with FLOVENT DISKUS is not recommended because increased systemic corticosteroid adverse effects may occur.
Source: FDA drug label - fluticasone propionate
The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with Fluticasone Propionate/Salmeterol MDPI is not recommended because increased systemic corticosteroid and increased cardiovascular adverse effects may occur. The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with Fluticasone Propionate/Salmeterol MDPI is not recommended because increased systemic corticosteroid and increased cardiovascular adverse effects may occur.
Source: FDA drug label - fluticasone propionate and salmeterol
The following are examples of medications that may increase the glucose-lowering effect of sulfonylureas including glimepiride, increasing the susceptibility to and/or intensity of hypoglycemia: oral anti-diabetic medications, pramlintide acetate, insulin, angiotensin converting enzyme (ACE) inhibitors, H 2 receptor antagonists, fibrates, propoxyphene, pentoxifylline, somatostatin analogs, anabolic steroids and androgens, cyclophosphamide, phenyramidol, guanethidine, fluconazole, sulfinpyrazone, tetracyclines, clarithromycin, disopyramide, quinolones, and those drugs that are highly protein-bound, such as fluoxetine, nonsteroidal anti-inflammatory drugs, salicylates, sulfonamides, chloramphenicol, coumarins, probenecid and monoamine oxidase inhibitors.
Source: FDA drug label - glimepiride
Based on simulations of these results, a reduction of the KALYDECO dosage is recommended for patients aged 6 months and older taking concomitant strong CYP3A inhibitors, such as ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, and clarithromycin.
Source: FDA drug label - ivacaftor
Intervention : See Contraindications and Warnings and Precautions in prescribing information for clarithromycin.
Source: FDA drug label - lansoprazole
Co-administration of other strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin, cobicistat-containing products) with triamcinolone acetonide injectable suspension may cause increased plasma concentration of triamcinolone leading to adverse reactions (see ADVERSE REACTIONS ).
Source: FDA drug label - lidocaine hydrochloride, triamcinolone acetonide, povidone-iodine
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.
Source: FDA drug label - clarithromycin
Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, erythromycin, and cobicistat-containing products), and grapefruit juice increase the risk of myopathy by reducing the elimination of lovastatin (see CONTRAINDICATIONS , WARNINGS , Myopathy/Rhabdomyolysis , and CLINICAL PHARMACOLOGY , Pharmacokinetics ).
Source: FDA drug label - lovastatin
Co-administration of other strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin, cobicistat-containing products) with triamcinolone acetonide injectable suspension may cause increased plasma concentration of triamcinolone leading to adverse reactions (see ADVERSE REACTIONS ).
Source: FDA drug label - marcaine, kenalog, povidone iodine
Examples of some of the more potent CYP 3A4 inhibitors include macrolide antibiotics (e.g., erythromycin, troleandomycin, clarithromycin), HIV protease or reverse transcriptase inhibitors (e.g., ritonavir, indinavir, nelfinavir, delavirdine) or azole antifungals (e.g., ketoconazole, itraconazole, voriconazole).
Source: FDA drug label - methylergonovine maleate
CYP3A Inhibitors CYP3A inhibitors such as ketoconazole, fluconazole, itraconazole, clarithromycin, erythromycin (Azithromycin, although structurally related to the class of macrolide antibiotic is void of clinically relevant CYP3A4 inhibition), grapefruit, nefazodone, fluoxetine, saquinavir, indinavir, nelfinavir, and ritonavir may result in increased exposure to nifedipine when co-administered.
Source: FDA drug label - nifedipine
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.
Source: FDA drug label - clarithromycin
Other inhibitors of the cytochrome P450 3A4 enzyme system, such as antimycotic agents (e.g., itraconazole and miconazole) or macrolide antibiotics (e.g., erythromycin and clarithromycin), may alter oxybutynin mean pharmacokinetic parameters (i.e., C max and AUC).
Source: FDA drug label - oxybutynin chloride
Hence, exposure of paricalcitol will increase upon coadministration with strong CYP3A inhibitors such as but not limited to: boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole.
Source: FDA drug label - paricalcitol
(2.6, 7.1) Clarithromycin: combination increases exposure. 7.2 Clarithromycin and Other Macrolide Antibiotics The risk of myopathy/rhabdomyolysis is increased with concomitant administration of clarithromycin. Limit pravastatin to 40 mg once daily for concomitant use with clarithromycin [see Dosage and Administration (2.7) , Warnings and Precautions (5.1) , and Clinical Pharmacology (12.3) ].
Source: FDA drug label - pravastatin sodium
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.
Source: FDA drug label - clarithromycin
Decrease exposure Other Drugs Enalapril Decrease active metabolite exposure Chloramphenicol Concomitant use with rifampin in 2 children Decrease exposure Clarithromycin Decrease exposure Dapsone Rifampin has been shown to increase the clearance of dapsone and, accordingly, decrease dapsone exposure.
Source: FDA drug label - rifampin
Macrolide or ketolide antibiotics: azithromycin clarithromycin erythromycin ↑ rilpivirine ↔ azithromycin ↔ clarithromycin ↔ erythromycin Macrolides are expected to increase concentrations of rilpivirine and are associated with a risk of Torsade de Pointes [Warnings and Precautions (5.4)].
Source: FDA drug label - rilpivirine hydrochloride
Ritonavir Etravirine Ritonavir, Etravirine: (see Ritonavir and Etravirine under “Drugs That Affect Clarithromycin Tablets” in the table below) [see Pharmacokinetics ( 12.3 )] . 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 ( 12.3 )] . 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 ( 12.3 )] .
Source: FDA drug label - ritonavir
Although clarithromycin is a combined P-gp and strong CYP3A inhibitor, pharmacokinetic data suggests that no precautions are necessary with concomitant administration with XARELTO as the change in exposure is unlikely to affect the bleeding risk [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - rivaroxaban
Examples Boceprevir, clarithromycin, cobicistat, conivaptan, danoprevir and ritonavir, diltiazem, elvitegravir and ritonavir, grapefruit juice a , idelalisib, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, nefazodone, nelfinavir, paritaprevir and ritonavir and (ombitasvir and/or dasabuvir), posaconazole, ritonavir, saquinavir and ritonavir, tipranavir and ritonavir, troleandomycin, voriconazole Strong CYP3A Inducers Clinical Impact Coadministration of RYDAPT with strong CYP3A inducers may decrease midostaurin concentrations [see Clinical Pharmacology (12.3)].
Source: FDA drug label - rydapt
The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with SEREVENT DISKUS is not recommended because increased cardiovascular adverse effects may occur.
Source: FDA drug label - salmeterol xinafoate
Examples: Select azole anti-fungals (e.g., itraconazole, ketoconazole, posaconazole, and voriconazole), select macrolide antibiotics (e.g., erythromycin and clarithromycin), select HIV protease inhibitors (e.g., nelfinavir, ritonavir, and darunavir/ritonavir), select HCV protease inhibitors (e.g., boceprevir and telaprevir), cobicistat-containing products, and nefazodone.
Source: FDA drug label - simvastatin
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.
Source: FDA drug label - clarithromycin
40% increase Clarithromycin Similar to erythromycin.
Source: FDA drug label - theophylline
40% increase Clarithromycin Similar to erythromycin.
Source: FDA drug label - theophylline anhydrous
Antimycobacterials: Clarithromycin ↑ Tipranavir, ↑ Clarithromycin, ↓ 14-hydroxy-clarithromycin metabolite No dose adjustment of APTIVUS or clarithromycin for patients with normal renal function is necessary. For patients with renal impairment the following dosage adjustments should be considered: For patients with CL CR 30 to 60 mL/min the dose of clarithromycin should be reduced by 50%. For patients with CL CR <30 mL/min the dose of clarithromycin should be decreased by 75%.
Source: FDA drug label - tipranavir
For patients receiving ketoconazole or other potent CYP3A4 inhibitors such as itraconazole, clarithromycin, or ritonavir, the recommended dose of tolterodine tartrate extended-release capsules is 2 mg once daily [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3) ] . For patients receiving ketoconazole or other potent CYP3A4 inhibitors such as itraconazole, miconazole, clarithromycin, ritonavir, the recommended dose of tolterodine tartrate extended-release capsules is 2 mg daily [see Dosage and Administration (2.3) ] .
Source: FDA drug label - tolterodine tartrate
Examples: itraconazole, ketoconazole, clarithromycin, indinavir Strong CYP3A4 Inducers Clinical Impact: The concomitant use of trazodone and strong CYP3A4 inducers decreased the exposure of trazodone compared to the use of trazodone alone .
Source: FDA drug label - trazodone hydrochloride
Co-administration of other strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin, cobicistat-containing products) with Kenalog-40 Injection may cause increased plasma concentration of triamcinolone leading to adverse reactions.
Source: FDA drug label - triamcinolone acetonide
Strong CYP3A4 Inhibitors (e.g., itraconazole, clarithromycin, voriconazole) The concomitant use of vilazodone hydrochloride tablets and strong CYP3A4 inhibitors increased the exposure of vilazodone compared to the use of vilazodone hydrochloride tablets alone [see Clinical Pharmacology (12.3)].
Source: FDA drug label - vilazodone hydrochloride
Table 2: Examples of CYP450 Interactions with Warfarin Enzyme Inhibitors Inducers CYP2C9 amiodarone, capecitabine, cotrimoxazole, etravirine, fluconazole, fluvastatin, fluvoxamine, metronidazole, miconazole, oxandrolone, sulfinpyrazone, tigecycline, voriconazole, zafirlukast aprepitant, bosentan, carbamazepine, phenobarbital, rifampin CYP1A2 acyclovir, allopurinol, caffeine, cimetidine, ciprofloxacin, disulfiram, enoxacin, famotidine, fluvoxamine, methoxsalen, mexiletine, norfloxacin, oral contraceptives, phenylpropanolamine, propafenone, propranolol, terbinafine, thiabendazole, ticlopidine, verapamil, zileuton montelukast, moricizine, omeprazole, phenobarbital, phenytoin, cigarette smoking CYP3A4 alprazolam, amiodarone, amlodipine, amprenavir, aprepitant, atorvastatin, atazanavir, bicalutamide, cilostazol, cimetidine, ciprofloxacin, clarithromycin, conivaptan, cyclosporine, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fluoxetine, fluvoxamine, fosamprenavir, imatinib, indinavir, isoniazid, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, nilotinib, oral contraceptives, posaconazole, ranitidine, ranolazine, ritonavir, saquinavir, telithromycin, tipranavir, voriconazole, zileuton armodafinil, amprenavir, aprepitant, bosentan, carbamazepine, efavirenz, etravirine, modafinil, nafcillin, phenytoin, pioglitazone, prednisone, rifampin, rufinamide 7.3 Drugs that Increase Bleeding Risk Examples of drugs known to increase the risk of bleeding are presented in Table 3 .
Source: FDA drug label - warfarin sodium