Nifedipine

Telaprevir Decrease AUC by 92% Systemic Hormonal Contraceptives Prevention or Management Advise patients to change to non-hormonal methods of birth control during rifampin therapy Estrogens Decrease exposure Progestins Anticonvulsants Phenytoin § Decrease exposure § Antiarrhythmics Disopyramide Decrease exposure Mexiletine Decrease exposure Quinidine Decrease exposure Propafenone Decrease AUC by 50% to 67% Tocainide Decrease exposure Antiestrogens Tamoxifen Decrease AUC by 86% Toremifene Decrease steady state concentrations of toremifene in serum Antithrombotic Agents Clopidogrel Prevention or Management Concomitant use of clopidogrel and rifampin should be discouraged Increase active metabolite exposure and risk of bleeding Ticagrelor Prevention or Management Avoid use Decrease exposure Antipsychotics Haloperidol Decrease plasma concentrations by 70% Lurasidone Prevention or Management: Concomitant use is contraindicated (See CONTRADICTIONS ) Decrease exposure Oral Anticoagulants Prevention or Management Perform prothrombin time daily or as frequently as necessary to establish and maintain the required dose of anticoagulant Warfarin Decrease exposure Antifungals Fluconazole Decrease AUC by 23% Itraconazole Prevention or Management Not recommended 2 weeks before and during itraconazole treatment Decrease exposure Ketoconazole Decrease exposure Beta-blockers Metoprolol Decrease exposure Propranolol Decrease exposure Benzodiazepines Diazepam *,¶ Decrease exposure Benzodiazepine-Related Drugs Zopiclone Decrease AUC by 82% Zolpidem Decrease AUC by 73% Calcium Channel Blockers ¶ Diltiazem Decrease exposure Nifedipine # Decrease exposure Verapamil Decrease exposure Corticosteroids Þ Prednisolone Decrease exposure Cardiac Glycosides Digoxin Prevention or Management Measure serum digoxin concentrations before initiating rifampin. ‡ Administered with rifampin 300 mg daily § Administered with rifampin 450 mg daily ¶ Administered with rifampin 1200 mg daily # Rifampin 1200 mg administered as a single oral dose 8 hours before administering a single oral dose of nifedipine 10 mg Þ Numerous cases in the literature describe a decrease in glucocorticoid effect when used concomitantly with rifampin.

Strong CYP3A inducer reduces the bioavailability and efficacy of nifedipine; careful consideration needed if co-administered.

Significantly increases peak nifedipine plasma levels (80%) and AUC (74%). Cautious titration advised when initiating nifedipine in patients receiving cimetidine.

Prevention or Management Avoid co-administration of potent ENT1, CNT3, or BCRP transporter inhibitors (e.g., ritonavir, eltrombopag, curcumin, cyclosporine, dilazep, nifedipine, nimodipine, cilostazol, sulindac, dipyridamole, or reserpine) during the 4 to 5 day cladribine treatment cycles.

CYP3A inhibitor that may increase nifedipine exposure. Careful monitoring and dose adjustment necessary; consider lowest dose.

CYP3A inhibitor that may increase nifedipine exposure. Careful monitoring and dose adjustment necessary; consider lowest dose.

CYP3A inhibitor that may increase nifedipine exposure. Careful monitoring and dose adjustment necessary; consider lowest dose.

CYP3A inhibitor that may increase nifedipine exposure. Careful monitoring and dose adjustment necessary; consider lowest dose.

CYP3A inhibitor that may increase nifedipine exposure. Careful monitoring and dose adjustment necessary; consider lowest dose.

CYP3A inhibitor that may increase nifedipine exposure. Careful monitoring and dose adjustment necessary; consider lowest dose.

CYP3A inhibitor that may increase nifedipine exposure. Careful monitoring and dose adjustment necessary; consider lowest dose.

CYP3A inhibitor that may increase nifedipine exposure. Careful monitoring and dose adjustment necessary; consider lowest dose.

Exaggerated hypotensive response is possible with concomitant use. Monitor vital signs frequently; supportive care and/or discontinuation may be required.

An exaggerated hypotensive response is possible with concomitant use of magnesium sulfate and dihydropyridine calcium channel blockers.

CYP3A inhibitor that may increase nifedipine exposure. Careful monitoring and dose adjustment necessary; consider lowest dose.

CYP3A inhibitor that may increase nifedipine exposure. Careful monitoring and dose adjustment necessary; consider lowest dose.

Combination may increase likelihood of congestive heart failure, severe hypotension, or exacerbation of angina, though usually well tolerated.

Strong CYP3A inducer reduces the bioavailability and efficacy of nifedipine; careful consideration needed if co-administered.

Antagonistic effects with decreased phenylephrine blood pressure effect via calcium channel blockade.

Co-administration lowers systemic exposure to nifedipine by approximately 70%. Avoid co-administration or consider alternative antihypertensive therapy.

Strong CYP3A inducer reduces the bioavailability and efficacy of nifedipine; careful consideration needed if co-administered.

CYP3A inhibitor that may increase nifedipine exposure. Careful monitoring and dose adjustment necessary; consider lowest dose.

CYP3A inhibitor that may increase nifedipine exposure. Careful monitoring and dose adjustment necessary; consider lowest dose.

Strong CYP3A inducer reduces the bioavailability and efficacy of nifedipine; careful consideration needed if co-administered.

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., erythromycin, fluconazole), calcium channel blockers (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and Precautions (5.6, 5.11, 5.12)].

Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and Precautions ( 5.7 , 5.10 , 5.11 )] .

Hypotension more likely to occur when dihydropyridine calcium antagonist is added to beta-blocker therapy.

felodipine, nifedipine, nicardipine, and verapamil ↑ calcium channel blocker Caution is warranted.

felodipine, nifedipine, nicardipine, and verapamil ↑ calcium channel blocker Caution is warranted.

ACE inhibitor co-administered with nifedipine may result in pharmacodynamic interactions affecting blood pressure.

Calcium antagonist may be used with beta-blockers when heart function is normal but should be avoided with impaired cardiac function; hypotension more likely with dihydropyridines.

Cimetidine reduces hepatic metabolism of nifedipine, delaying elimination and increasing blood levels.

Isolated reports of elevated digoxin levels with possible interaction. Monitor digoxin levels when initiating, adjusting, or discontinuing nifedipine.

Administration with nifedipine increased digoxin levels by average 45% in some studies. Monitor digoxin levels when initiating, adjusting, or discontinuing nifedipine to avoid over- or under-digitalization.

CYP3A inhibitor that increases nifedipine AUC by factors of 2.2 to 3.1 and C max by factors of 1.7 to 2.0. Caution should be exercised and dose reduction of nifedipine considered.

Calcium Channel Blockers: e.g., amlodipine diltiazem felodipine nicardipine nifedipine verapamil ↑ calcium channel blockers Caution is warranted and clinical monitoring is recommended upon coadministration of calcium channel blockers with GENVOYA.

Insufficient experience with concomitant use with nifedipine; concurrent use not recommended.

Calcium channel blockers: Diltiazem, felodipine, nifedipine, nicardipine, nimodipine, verapamil, amlodipine, nisoldipine, isradipine ↑ Calcium channel blockers Use with caution.

Phenytoin when given with the combination of fosamprenavir and ritonavir may increase the concentration of amprenavir Calcium channel blockers Nifedipine, nimodipine, nisoldipine, verapamil Other Albendazole (decreases active metabolite), chlorpropamide, clozapine, cyclosporine, digoxin, disopyramide, folic acid, methadone, mexiletine, praziquantel, quetiapine 7.3 Hyperammonemia with Concomitant Use of Valproate Concomitant administration of phenytoin and valproate has been associated with an increased risk of valproate-associated hyperammonemia.

Grapefruit juice approximately doubles nifedipine AUC and Cmax with no change in half-life.

Nifedipine may be safely co-administered with nitrates, but no controlled studies evaluate antianginal effectiveness of combination.

Nifedipine increased metformin plasma Cmax by 20% and AUC by 9%, with increased urinary excretion. Tmax and half-life unaffected. Metformin had minimal effects on nifedipine.

7 DRUG INTERACTIONS Monitor for sirolimus, itraconazole or nifedipine toxicity and dosage of sirolimus, itraconazole or nifedipine should be reduced, if necessary. Co-administration of Micafungin with Other Drugs Co-administration of micafungin with mycophenolate mofetil (MMF), amphotericin B, tacrolimus, prednisolone, sirolimus and nifedipine did not alter the pharmacokinetics of micafungin. Nifedipine AUC and C max were increased by 18% and 42%, respectively, in the presence of steady-state micafungin compared with nifedipine alone.

7 DRUG INTERACTIONS Monitor for sirolimus, itraconazole or nifedipine toxicity, and dosage of sirolimus, itraconazole or nifedipine should be reduced, if necessary. CYP2C19 and CYP3A4 Inducer Co-administration of micafungin with rifampin and ritonavir did not alter the pharmacokinetics of micafungin Co-administration of Micafungin with Other Drugs Co-administration of micafungin with mycophenolate mofetil (MMF), amphotericin B, tacrolimus, prednisolone, sirolimus and nifedipine did not alter the pharmacokinetics of micafungin. Nifedipine AUC and C max were increased by 18% and 42%, respectively, in the presence of steady-state micafungin compared with nifedipine alone.

Calcium channel blockers amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil ↑ calcium channel blocker Caution is warranted and clinical monitoring of patients is recommended.

Nifedipine may be safely co-administered with long-acting nitrates, but no controlled studies have evaluated antianginal effectiveness of this combination.

Rare reports of increased prothrombin time in patients taking coumarin anticoagulants with nifedipine, though relationship uncertain.

Small decreases in blood pressure observed in some patients. Periodic systemic blood pressure monitoring recommended.

Phenytoin when given with the combination of fosamprenavir and ritonavir may increase the concentration of amprenavir Calcium channel blockers Nifedipine, nimodipine, nisoldipine, verapamil Other Albendazole (decreases active metabolite), chlorpropamide, clozapine, cyclosporine, digoxin, disopyramide, folic acid, methadone, mexiletine, praziquantel, quetiapine 7.3 Hyperammonemia with Concomitant Use of Valproate Concomitant administration of phenytoin and valproate has been associated with an increased risk of valproate-associated hyperammonemia.

Prevention or Management Verapamil, Diltiazem, Nifedipine, Nicardipine, Felodipine Monitor frequently for adverse reactions and toxicity with concomitant use of posaconazole with calcium channel blockers that are CYP3A4 substrates.

Propranolol increases nifedipine Cmax by 64% and AUC by 79%.

CYP3A substrate and inhibitor that increases nifedipine C max and AUC by 2.30 and 1.37 fold respectively, with increased heart rate up to 17.9 beats/minute. Heart rate monitoring and nifedipine dose adjustment recommended.

Calcium channel blockers: diltiazem, nifedipine, verapamil ↑ calcium channel blockers Caution is warranted and clinical monitoring of patients is recommended.

In vitro data of benzodiazepines suggest possible drug interaction with triazolam. Caution recommended.

CYP3A inhibitor that increases nifedipine exposure during concomitant therapy. Blood pressure should be monitored and dose reduction of nifedipine considered.

Nifedipine A single-dose, metformin-nifedipine drug interaction study in normal healthy volunteers demonstrated that coadministration of nifedipine increased plasma metformin C max and AUC by 20% and 9%, respectively, and increased the amount excreted in the urine. Nifedipine appears to enhance the absorption of metformin. Metformin had minimal effects on nifedipine.

Nifedipine A single-dose, metformin-nifedipine drug interaction study in normal healthy volunteers demonstrated that coadministration of nifedipine increased plasma metformin C max and AUC by 20% and 9%, respectively, and increased the amount excreted in the urine. Nifedipine appears to enhance the absorption of metformin. Metformin had minimal effects on nifedipine.

In vitro studies suggest CYP 2C9 inhibition, but in clinical studies nifedipine showed no clinically significant effect on irbesartan pharmacokinetics or pharmacodynamics.

No significant interaction observed with midazolam in healthy subjects.

No interaction observed in healthy subjects between midazolam and nifedipine.

No effect of miglitol was observed on the pharmacokinetics or pharmacodynamics of nifedipine.

Nifedipine very rarely decreases quinidine levels by unknown mechanisms.

Very rarely decreases quinidine levels by mechanisms not understood.

Produces smaller, non-significant increases in nifedipine levels compared to cimetidine.

Data from in vitro studies of benzodiazepines other than alprazolam suggest a possible drug interaction for the following: ergotamine, cyclosporine, amiodarone, nicardipine, and nifedipine.

Data from in vitro studies of benzodiazepines other than alprazolam suggest a possible drug interaction between benzodiazepines and the following: ergotamine, cyclosporine, amiodarone, nicardipine, and nifedipine [see Warnings and Precautions (5.8)].

albuterol, systemic and inhaled amoxicillin ampicillin, with or without sulbactam atenolol azithromycin caffeine, dietary ingestion cefaclor co-trimoxazole (trimethoprim and sulfamethoxazole) diltiazem dirithromycin enflurane famotidine felodipine finasteride hydrocortisone isoflurane isoniazid isradipine influenza vaccine ketoconazole lomefloxacin mebendazole medroxyprogesterone methylprednisolone metronidazole metoprolol nadolol nifedipine nizatidine norfloxacin ofloxacin omeprazole prednisone, prednisolone ranitidine rifabutin roxithromycin sorbitol (purgative doses do not inhibit theophylline absorption) sucralfate terbutaline, systemic terfenadine tetracycline tocainide The Effect of Other Drugs on Theophylline Serum Concentration Measurements: Most serum theophylline assays in clinical use are immunoassays which are specific for theophylline.

Antiviral Drugs Amprenavir, atanazavir, delavirine, fosamprinavir, indinavir, nelfinavir and ritonavir , as CYP3A inhibitors, can inhibit the metabolism of nifedipine and increase the exposure to nifedipine.

Calcium channel blockers: (e.g., amlodipine, diltiazem, felodipine, nifedipine, and verapamil) ↑ calcium channel blocker Clinical monitoring is recommended for coadministration with calcium channel blockers metabolized by CYP3A.

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.

The pharmacokinetics of benazepril are not affected by the following drugs: hydrochlorothiazide, furosemide, chlorthalidone, digoxin, propranolol, atenolol, nifedipine, amlodipine, naproxen, acetylsalicylic acid, or cimetidine.

Candesartan: No significant drug interaction has been reported in studies with candesartan cilexitil given together with nifedipine. Because candesartan is not significantly metabolized by the cytochrome P450 system and at therapeutic concentrations has no effect on cytochrome P450 enzymes, interactions with drugs that inhibit or are metabolized by those enzymes would not be expected.

Calcium Channel Blockers: e.g., amlodipine diltiazem felodipine nifedipine verapamil ↑ calcium channel blockers Clinical monitoring is recommended for coadministration with calcium channel blockers metabolized by CYP3A.

Nifedipine Frequent gingival hyperplasia when nifedipine is given concurrently with cyclosporine has been reported. The concomitant use of nifedipine should be avoided in patients in whom gingival hyperplasia develops as a side effect of cyclosporine.

Calcium Channel Blockers : amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil ↑ calcium channel blockers Clinical monitoring of patients is recommended.

Calcium Channel Blockers: amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil ↑ calcium channel blockers Clinical monitoring of patients is recommended.

amlodipine, diltiazem, felodipine, nifedipine, verapamil ↑ calcium channel blockers Clinical monitoring is recommended for co-administration with calcium channel blockers metabolized by CYP3A.

Calcium channel blockers: e.g., amlodipine, diltiazem, felodipine, nifedipine, verapamil ↑ calcium channel blockers Clinical monitoring is recommended for co-administration with calcium channel blockers metabolized by CYP3A.

Central Alpha1-Blockers Doxazosin: Healthy volunteers participating in a multiple dose doxazosin-nifedipine interaction study received 2 mg doxazosin q.d. Co-administration of nifedipine resulted in a decrease in AUC and C max of doxazosin to 83% and 86% of the values in the absence of nifedipine, respectively. In the presence of doxazosin, AUC and C max of nifedipine were increased by factors of 1.13 and 1.23, respectively.

Calcium Channel Blockers Dronedarone increased the exposure of calcium channel blockers (verapamil, diltiazem or nifedipine).

7.3 Nifedipine, Atenolol, Enalapril Tamsulosin Dosage adjustments are not necessary when tamsulosin is administered concomitantly with nifedipine, atenolol, or enalapril [see Clinical Pharmacology ( 12.3 ) ] .

Others (e.g., felodipine, nicardipine, nifedipine, verapamil) ↓ calcium channel blocker When co-administered with efavirenz, dosage adjustment of calcium channels blocker may be needed and should be guided by clinical response (refer to the full prescribing information for the calcium channel blocker).

Others e.g., felodipine nicardipine nifedipine verapamil ↓ calcium channel blocker No data are available on the potential interactions of EFV with other calcium channel blockers that are substrates of CYP3A.

Calcium channel blockers: Diltiazem Others (e.g., felodipine, nicardipine, nifedipine, verapamil) ↓diltiazem* ↓desacetyl diltiazem* ↓N-monodesmethyldiltiazem* ↓calcium channel blocker Diltiazem dose adjustments should be guided by clinical response (refer to the full prescribing information for diltiazem).

Calcium Channel Blockers: e.g., amlodipine diltiazem felodipine nicardipine nifedipine verapamil ↑ calcium channel blockers Clinical monitoring is recommended upon coadministration of calcium channel blockers with STRIBILD.

There has been too little experience with the coadministration of flecainide acetate with nifedipine or diltiazem to recommend concomitant use.

Antiviral Drugs Amprenavir, atanazavir, delavirine, fosamprinavir, indinavir, nelfinavir and ritonavir , as CYP3A inhibitors, can inhibit the metabolism of nifedipine and increase the exposure to nifedipine.

In separate single or multiple dose pharmacokinetic interaction studies with chlorthalidone, nifedipine, propranolol, hydrochlorothiazide, cimetidine, metoclopramide, propantheline, digoxin, and warfarin, the bioavailability of fosinoprilat was not altered by coadministration of fosinopril with any one of these drugs.

In separate single or multiple dose pharmacokinetic interaction studies with chlorthalidone, nifedipine, propranolol, hydrochlorothiazide, cimetidine, metoclopramide, propantheline, digoxin, and warfarin, the bioavailability of fosinoprilat was not altered by coadministration of fosinopril with any one of these drugs.

Other The bioavailability of unbound fosinoprilat is not altered by coadministration of fosinopril with aspirin, chlorthalidone, cimetidine, digoxin, metoclopramide, nifedipine, propranolol, propantheline, or warfarin .

Nifedipine Nifedipine : Nifedipine is a substrate for 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 ).

Examples: diltiazem, nifedipine, verapamil Atypical and Typical Antipsychotic Drugs Clinical Impact: Reports of neurotoxic reactions in patients treated with both lithium and an antipsychotic, ranging from extrapyramidal symptoms to neuroleptic malignant syndrome, as well as reports of an encephalopathic syndrome in few patients treated with concomitant therapy [see Warnings and Precautions ( 5.5 )].

felodipine, nifedipine, nicardipine ↑ dihydropyridine calcium channel blockers Clinical monitoring of patients is recommended and a dose reduction of the dihydropyridine calcium channel blocker may be considered.

Warn patients against excessive alcohol intake ( 7 ) Drug Interactions In Vivo Assessment of Drug Interactions Table 5: Effect of Coadministered Drug on Plasma Metformin Systemic Exposure Coadministered Drug Dose of Coadministered Drug All metformin hydrochloride and coadministered drugs were given as single doses Dose of Metformin Hydrochloride Geometric Mean Ratio (ratio with/without coadministered drug) No Effect = 1.00 AUC AUC = AUC inf C max No dosing adjustments required for the following: Glyburide 5 mg 850 mg metformin 0.91 Ratio of arithmetic means 0.93 Furosemide 40 mg 850 mg metformin 1.09 1.22 Nifedipine 10 mg 850 mg metformin 1.16 1.21 Propranolol 40 mg 850 mg metformin 0.90 0.94 Ibuprofen 400 mg 850 mg metformin 1.05 1.07 Cationic drugs eliminated by renal tubular secretion may reduce metformin elimination [ See Warnings and Precautions (5.1) and Drug Interactions (7) . ] Cimetidine 400 mg 850 mg metformin 1.40 1.61 Carbonic anhydrase inhibitors may cause metabolic acidosis [ See Warnings and Precautions (5.1) and Drug Interactions (7) .] Topiramate 5 mg At steady state with topiramate 100 mg every 12 hours and metformin 500 mg every 12 hours; AUC = AUC 0-12h 5 mg metformin 1.25 1.17 Table 6: Effect of Metformin on Coadministered Drug Systemic Exposure Coadministered Drug Dose of Coadministered Drug All metformin hydrochloride and coadministered drugs were given as single doses Dose of Metformin Hydrochloride Geometric Mean Ratio (ratio with/without metformin) No Effect = 1.00 AUC AUC = AUC inf unless otherwise noted C max No dosing adjustments required for the following: Glyburide 5 mg 850 mg glyburide 0.78 Ratio of arithmetic means, p-value of difference < 0.05 0.63 Furosemide 40 mg 850 mg furosemide 0.87 0.69 Nifedipine 10 mg 850 mg nifedipine 1.10 AUC 0-24hr reported 1.08 Propranolol 40 mg 850 mg propranolol 1.01 1.02 Ibuprofen 400 mg 850 mg ibuprofen 0.97 Ratio of arithmetic means 1.01 Cimetidine 400 mg 850 mg cimetidine 0.95 1.01

No interaction was observed in healthy subjects between midazolam and nifedipine.

Calcium Channel blockers: Diltiazem, nifedipine, verapamil Plasma concentrations may be decreased.

Antisecretory Drugs Omeprazole: In healthy volunteers receiving a single dose of 10 mg nifedipine, AUC and C max of nifedipine after pretreatment with omeprazole 20 mg q.d. Pretreatment with or co-administration of omeprazole did not impact the effect of nifedipine on blood pressure or heart rate. The impact of omeprazole on nifedipine is not likely to be of clinical relevance.

Pantoprazole: In healthy volunteers the exposure to neither drug was changed significantly in the presence of the other drug.

7.11 Calcium Channel Blockers Metabolized by CYP3A4 Posaconazole may increase the plasma concentrations of calcium channel blockers metabolized by CYP3A4 (e.g., verapamil, diltiazem, nifedipine, nicardipine, felodipine).

7.10 Antihypertensive Drugs Due to the antagonistic pharmacologic effects of phenylephrine, one of the active ingredients in Promethazine and Phenylephrine HCl and Codeine Phosphate Oral Solution, the concomitant use of Promethazine and Phenylephrine HCl and Codeine Phosphate Oral Solution with antihypertensive drugs, including alpha-adrenergic antagonists (e.g., phentolamine); mixed alpha- and beta-adrenoreceptor antagonists; calcium channel blockers (e.g., nifedipine); ACE inhibitors; and centrally acting sympatholytic agents (e.g., guanfacine, reserpine) may reduce their antihypertensive effects.

Table 4: Drug Interactions with PRIFTIN: Dosage Adjustment May be Necessary Drug Class Examples of Drugs Within Class Antiarrhythmics Disopyramide, mexiletine, quinidine, tocainide Antibiotics Chloramphenicol, clarithromycin, dapsone, doxycycline; Fluoroquinolones (such as ciprofloxacin) Oral Anticoagulants Warfarin Anticonvulsants Phenytoin Antimalarials Quinine Azole Antifungals Fluconazole, itraconazole, ketoconazole Antipsychotics Haloperidol Barbiturates Phenobarbital Benzodiazepines Diazepam Beta-Blockers Propranolol Calcium Channel Blockers Diltiazem, nifedipine, verapamil Cardiac Glycoside Preparations Digoxin Corticosteroids Prednisone Fibrates Clofibrate Oral Hypoglycemics Sulfonylureas (e.g., glyburide, glipizide) Hormonal Contraceptives/Progestins Ethinyl estradiol, levonorgestrel Immunosuppressants Cyclosporine, tacrolimus Methylxanthines Theophylline Narcotic analgesics Methadone Phosphodiesterase-5 (PDE-5) Inhibitors Sildenafil Thyroid preparations Levothyroxine Tricyclic antidepressants Amitriptyline, nortriptyline 7.5 Other Interactions The conversion of PRIFTIN to 25-desacetyl rifapentine is mediated by an esterase enzyme.

7 DRUG INTERACTIONS Table 1 Oral drugs that can be administered concomitantly with Velphoro Calcitriol Ciprofloxacin Digoxin Enalapril Furosemide HMG-CoA reductase inhibitors Hydrochlorothiazide Losartan Metoprolol Nifedipine Omeprazole Quinidine Warfarin Oral drugs that are to be separated from Velphoro Dosing Recommendations Doxycycline Acetylsalicylic acid Cephalexin Take at least 1 hour before Velphoro. Velphoro can be administered concomitantly with oral calcitriol, ciprofloxacin, digoxin, enalapril, furosemide, HMG‑CoA reductase inhibitors, hydrochlorothiazide, losartan, metoprolol, nifedipine, omeprazole, quinidine and warfarin.

7.5 Nifedipine, Atenolol, Enalapril Dosage adjustments are not necessary when tamsulosin hydrochloride capsules are administered concomitantly with nifedipine, atenolol, or enalapril [see Clinical Pharmacology (12.3)].

Drugs that have been documented not to interact with theophylline or drugs that produce no clinically significant interaction with theophylline.* albuterol, systemic and inhaled mebendazole amoxicillin medroxyprogesterone ampicillin, with or without methylprednisolone sulbactam metronidazole atenolol metoprolol azithromycin nadolol caffeine, dietary ingestion nifedipine cefaclor nizatidine co-trimoxazole (trimethoprim and sulfamethoxazole) norfloxacin ofloxacin diltiazem omeprazole dirithromycin prednisone, prednisolone enflurane ranitidine famotidine rifabutin felodipine roxithromycin finasteride Sorbitol (purgative doses do not inhibit hydrocortisone theophylline absorption) isoflurane sucralfate isoniazid terbutaline, systemic isradipine terfenadine influenza vaccine tetracycline ketoconazole tocainide lomefloxacin * Refer to PRECAUTIONS, Drug Interactions for information regarding table.

albuterol, systemic and inhaled mebendazole amoxicillin medroxyprogesterone ampicillin, with or without sulbactam methylprednisolone atenolol metronidazole azithromycin metoprolol caffeine, dietary ingestion nadolol cefaclor nifedipine co-trimoxazole (trimethoprim and sulfamethoxazole) nizatidine diltiazem norfloxacin dirithromycin ofloxacin enflurane omeprazole famotidine prednisone, prednisolone felodipine ranitidine finasteride rifabutin hydrocortisone roxithromycin isoflurane Sorbitol (purgative doses do not inhibit theophylline absorption) isoniazid sucralfate isradipine terbutaline, systemic influenza vaccine terfenadine ketoconazole tetracycline lomefloxacin tocainide

Timolol: Hypotension is more likely to occur if dihydropryridine calcium antagonists such as nifedipine are co-administered with timolol.

Other (Trandolapril Component) No clinically significant pharmacokinetic interaction has been found between trandolapril (or its metabolites) and nifedipine.

In vivo studies Nifedipine: Vardenafil 20 mg (film-coated tablets), when co-administered with slow-release nifedipine 30 mg or 60 mg once daily, did not affect the relative AUC or C max of nifedipine, a drug that is metabolized via CYP3A4. Nifedipine did not alter the plasma levels of vardenafil when taken in combination. Vardenafil orally disintegrating tablet, when co-administered with slow-release nifedipine 30 mg or 60 mg once daily in patients whose hypertension was controlled with nifedipine, produced mean additional supine systolic/diastolic blood pressure reductions of 3/4 mmHg (age group 65 to 69 years) and 5/5 mmHg (age group 70 to 80 years) compared to placebo.

In vivo studies Nifedipine: Vardenafil 20 mg, when co-administered with slow-release nifedipine 30 mg or 60 mg once daily, did not affect the AUC or C max of nifedipine, a drug that is metabolized via CYP3A4. Nifedipine did not alter the plasma levels of vardenafil hydrochloride tablets when taken in combination. In these patients whose hypertension was controlled with nifedipine, vardenafil hydrochloride tablets 20 mg produced mean additional supine systolic/diastolic blood pressure reductions of 6/5 mmHg compared to placebo.

Amlodipine Diltiazem Nifedipine Ergot Alkaloids Clinical Effect Clarithromycin is a strong CYP3A inhibitor.