Fosamprenavir

Use of colchicine in conjunction with P-gp or strong CYP3A4 inhibitors (this includes all protease inhibitors except fosamprenavir) is contraindicated in patients with renal or hepatic impairment [see Contraindications ( 4 )].

Famotidine reduces gastric acidity and may significantly reduce fosamprenavir absorption, leading to loss of efficacy.

Moderate CYP3A4 inhibitor; concomitant use is contraindicated due to increased risk of hypotension and syncope.

Concomitant use of moderate CYP3A4 inhibitors (such as amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, verapamil) has not been studied, but concomitant use with lomitapide is contraindicated since lomitapide exposure will likely increase significantly in the presence of these inhibitors.

Concomitant use is contraindicated. Rifampin decreases fosamprenavir AUC by 82%.

No drug interaction studies have been conducted with amlodipine besylate and atorvastatin calcium and other drugs, although studies have been conducted in the individual amlodipine and atorvastatin components, as described below: Amlodipine Increased Risk of Myopathy and Rhabdomyolysis ( 2 , 5.1 , 7.3 , 12.3 ) Cyclosporine, tipranavir plus ritonavir, glecaprevir plus pibrentasvir Avoid atorvastatin Clarithromycin, itraconazole, saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir, elbasvir plus grazoprevir,letermovir Do not exceed 20 mg atorvastatin daily Nelfinavir Do not exceed 40 mg atorvastatin daily Lopinavir plus ritonavir, simeprevir, fibric acid derivatives, erythromycin, azole antifungals, lipid-modifying doses of niacin, colchicine Consider the risk/benefit of concomitant use with atorvastatin Other Lipid-Lowering Medications: Increased risk of myopathy (7) . In patients taking saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir,fosamprenavir plus ritonavir, elbasvir plus grazoprevir or letermovir, do not exceed atorvastatin 20 mg. Examples: Tipranavir plus ritonavir, glecaprevir plus pibrentasvir, lopinavir plus ritonavir, simeprevir, saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir, elbasvir plus grazoprevir, letermovir, nelfinavir, and ledipasvir plus sofosbuvir.

Significantly increases atorvastatin plasma levels. Do not exceed ATORVALIQ 20 mg.

Drug Interactions Associated with Increased Risk of Myopathy/Rhabdomyolysis ( 2.6 , 5.1 , 7 , 12.3 ) Interacting Agents Prescribing Recommendations Cyclosporine, HIV protease inhibitors (tipranavir plus ritonavir), hepatitis C protease inhibitor (telaprevir) Avoid atorvastatin HIV protease inhibitor (lopinavir plus ritonavir) Use with caution and lowest dose necessary Clarithromycin, itraconazole, HIV protease inhibitors (saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir) Do not exceed 20 mg atorvastatin daily HIV protease inhibitor (nelfinavir) Hepatitis C protease inhibitor (boceprevir) Do not exceed 40 mg atorvastatin daily • Other Lipid-Lowering Medications: Use with fibrate products or lipid-modifying doses (≥ 1 g/day) of niacin increases the risk of adverse skeletal muscle effects. In patients taking the HIV protease inhibitors saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, or fosamprenavir plus ritonavir, the dose of atorvastatin should not exceed 20 mg and should be used with caution [ see Dosage and Administration ( 2.6 ) and Warnings and Precautions ( 5.1 ) ].

Co-administration results in decreased amprenavir and lopinavir concentrations with increased rate of adverse reactions. Appropriate doses have not been established.

Strong CYP3A inhibitor may increase mifepristone plasma concentrations; limit mifepristone dose to 900 mg per day when used together.

Co-administration without ritonavir is not recommended due to decreased amprenavir levels and increased nevirapine exposure.

HIV protease inhibitor that may significantly decrease plasma concentrations of norethindrone and ethinyl estradiol, potentially diminishing contraceptive effectiveness.

HIV protease inhibitor combination that decreases plasma concentrations of estrogen and/or progestin, potentially diminishing contraceptive effectiveness.

Avoid concomitant use of TALICIA with amprenavir, indinavir, lopinavir/ritonavir, saquinavir/ritonavir, ritonavir, tipranavir/ritonavir, fosamprenavir/ritonavir, or nelfinavir [see Warnings and Precautions (5.7) ] .

Interaction Drug Interaction Rifabutin, phenytoin, efavirenz, cimetidine, esomeprazole* Avoid coadministration unless the benefit outweighs the risks ( 7.6 , 7.7 , 7.8 , 7.9 ) Other drugs metabolized by CYP3A4 Consider dosage adjustment and monitor for adverse effects and toxicity ( 7.1 , 7.10 , 7.11 ) Digoxin Monitor digoxin plasma concentrations ( 7.12 ) Fosamprenavir, metoclopramide* Monitor for breakthrough fungal infections ( 7.6 , 7.13 ) *The drug interactions with esomeprazole and metoclopramide do not apply to posaconazole tablets. Fosamprenavir: Combining fosamprenavir with posaconazole may lead to decreased posaconazole plasma concentrations.

Interaction Drug Interaction Rifabutin, phenytoin, efavirenz, cimetidine Avoid coadministration unless the benefit outweighs the risks ( 7.6 , 7.7 , 7.8 , 7.9 ) Other drugs metabolized by CYP3A4 Consider dosage adjustment and monitor for adverse effects and toxicity ( 7.1 , 7.10 , 7.11 ) Digoxin Monitor digoxin plasma concentrations ( 7.12 ) Fosamprenavir Monitor for breakthrough fungal infections ( 7.6 , 7.13 ) 7.1 Immunosuppressants Metabolized by CYP3A4 Sirolimus: Concomitant administration of posaconazole with sirolimus increases the sirolimus blood concentrations by approximately 9-fold and can result in sirolimus toxicity. Fosamprenavir: Combining fosamprenavir with posaconazole may lead to decreased posaconazole plasma concentrations.

Fosamprenavir/ritonavir increases rifabutin AUC by 35% and Cmax by 36%. Reduce rifabutin dose by at least 75% (maximum 150 mg every other day or three times per week).

Co-administration increases amprenavir concentration. See complete prescribing information for fosamprenavir for dosing details.

Ritonavir increases fosamprenavir and amprenavir plasma concentrations. See complete prescribing information for fosamprenavir for co-administration details.

Moderate CYP3A4 inhibitors (e.g., erythromycin, amprenavir, aprepitant, diltiazem, fluconazole, fosamprenavir, and verapamil) would be expected to have similar effects.

Coadministration with TYBOST is not recommended because pharmacokinetic data are not available to provide appropriate dosing recommendations.

Moderate CYP3A4 Inhibitors amprenavir aprepitant diltiazem erythromycin fluconazole, fosamprenavir (prodrug of amprenavir) verapamil Significant increase in colchicine plasma concentration is anticipated.

HIV protease inhibitor that may decrease plasma concentrations of estrogen and/or progestin, potentially diminishing contraceptive effectiveness.

Protease inhibitors: Fosamprenavir/ritonavir a Tipranavir/ritonavir a ↓Dolutegravir Adjust dose of TIVICAY to twice daily for treatment-naïve and treatment-experienced, INSTI-naïve adult patients.

HIV protease inhibitor combination that may decrease plasma concentrations of etonogestrel.

Drugs That Affect Phenytoin Concentrations Interacting Agent Examples Drugs that may increase phenytoin serum levels Antiepileptic drugs Ethosuximide, felbamate, oxcarbazepine, methsuximide, topiramate Azoles Fluconazole, ketoconazole, itraconazole, miconazole, voriconazole Antineoplastic agents Capecitabine, fluorouracil Antidepressants Fluoxetine, fluvoxamine, sertraline Gastric acid reducing agents H 2 antagonists (cimetidine), omeprazole Sulfonamides Sulfamethizole, sulfaphenazole, sulfadiazine, sulfamethoxazole-trimethoprim Other Acute alcohol intake, amiodarone, chloramphenicol, chlordiazepoxide, disulfiram, estrogen, fluvastatin, isoniazid, methylphenidate, phenothiazines, salicylates, ticlopidine, tolbutamide, trazodone, warfarin Drugs that may decrease phenytoin serum levels Antineoplastic agents usually in combination Bleomycin, carboplatin, cisplatin, doxorubicin, methotrexate Antiviral agents Fosamprenavir, nelfinavir, ritonavir Antiepileptic drugs Carbamazepine, vigabatrin Other Chronic alcohol abuse, diazepam, diazoxide, folic acid, reserpine, rifampin, St. Carbamazepine, felbamate, lamotrigine, topiramate, oxcarbazepine, lacosamide Antiplatelets Ticagrelor Antilipidemic agents Atorvastatin, fluvastatin, simvastatin Antiviral agents Efavirenz, lopinavir/ritonavir, indinavir, nelfinavir, ritonavir, saquinavir Fosamprenavir: phenytoin when given with fosamprenavir alone may decrease the concentration of amprenavir, the active metabolite. 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.

Antivirals Cobicistat Darunavir (ritonavir-boosted) Elvitegravir (ritonavir-boosted) Fosamprenavir (ritonavir-boosted) Indinavira Ombitasvir/Paritaprevir/Ritonavir with or without Dasabuvir Ritonavir Saquinavir Monitor for adverse reactions.

Potent CYP3A4 inhibitor (when ritonavir-boosted) that may increase ketoconazole bioavailability. Should be used with caution and patients monitored closely.

HIV protease inhibitor (with ritonavir) may significantly decrease plasma concentrations of estrogen and/or progestin.

HIV protease inhibitor (with ritonavir) that may decrease plasma concentrations of estrogen and/or progestin.

HIV protease inhibitor that may decrease plasma concentrations of estrogen and/or progestin when used with ritonavir.

Significant decrease in systemic concentrations of norethindrone may occur.

HIV protease inhibitor that may decrease plasma concentrations of estrogen and/or progestin.

Phenytoin Decreased paroxetine exposure Fosamprenavir/Ritonavir Decreased plasma concentration of paroxetine Cimetidine Increased plasma concentration of paroxetine Use caution if co-administering paroxetine capsules with other drugs that inhibit CYP2D6 (e.g., quinidine).

Calcium carbonate, aluminum hydroxide, magnesium hydroxide Prevention or Management: Phenytoin and antacids should not be taken at the same time of day Antineoplastic agents usually in combination Bleomycin, carboplatin, cisplatin, doxorubicin, methotrexate Antiviral agents Fosamprenavir, nelfinavir, ritonavir Antiepileptic drugs Carbamazepine, vigabatrin Other Chronic alcohol abuse, diazepam, diazoxide, folic acid, reserpine, rifampin, St. Warfarin Increased and decreased PT/INR responses have been reported when phenytoin is coadministered with warfarin Other Corticosteroids, doxycycline, estrogens, furosemide, oral contraceptives, paroxetine, quinidine, rifampin, sertraline, theophylline, and vitamin D Drugs whose level is decreased by phenytoin Anticoagulants Apixaban, dabigatran, edoxaban, rivaroxaban Antiepileptic drugs The effect of phenytoin on phenobarbital, valproic acid and sodium valproate serum levels is unpredictable Carbamazepine, felbamate, lamotrigine, topiramate, oxcarbazepine, lacosamide Antilipidemic agents Atorvastatin, fluvastatin, simvastatin Antiplatelets Ticagrelor Antiviral agents Efavirenz, lopinavir/ritonavir, indinavir, nelfinavir, ritonavir, saquinavir Fosamprenavir: phenytoin when given with fosamprenavir alone may decrease the concentration of amprenavir, the active metabolite. 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.

Interacting Agent Examples Drugs that may increase phenytoin serum levels Antiepileptic drugs Ethosuximide, felbamate, oxcarbazepine, methsuximide, topiramate Azoles Fluconazole, ketoconazole, itraconazole, miconazole, voriconazole Antineoplastic agents Capecitabine, fluorouracil Antidepressants Fluoxetine, fluvoxamine, sertraline Gastric acid reducing agents H2 antagonists (cimetidine), omeprazole Sulfonamides Sulfamethizole, sulfaphenazole, sulfadiazine, sulfamethoxazole- trimethoprim Other Acute alcohol intake, amiodarone, chloramphenicol, chlordiazepoxide, disulfiram, estrogen, fluvastatin, isoniazid, methylphenidate, phenothiazines, salicylates, ticlopidine, tolbutamide, trazodone, warfarin Drugs that may decrease phenytoin serum levels Antacids a Calcium carbonate, aluminum hydroxide, magnesium hydroxide Prevention or Management: Phenytoin and antacids should not be taken at the same time of day Antineoplastic agents usually in combination Bleomycin, carboplatin, cisplatin, doxorubicin, methotrexate Antiviral agents Fosamprenavir, nelfinavir, ritonavir Antiepileptic drugs Carbamazepine, vigabatrin Other Chronic alcohol abuse, diazepam, diazoxide, folic acid, reserpine, rifampin, St. Warfarin Increased and decreased PT/INR responses have been reported when phenytoin is coadministered with warfarin Other Corticosteroids, doxycycline, estrogens, furosemide, oral contraceptives, paroxetine, quinidine, rifampin, sertraline, theophylline, and vitamin D Drugs whose level is decreased by phenytoin Anticoagulants Apixaban, dabigatran, edoxaban, rivaroxaban Antiepileptic drugs a Carbamazepine, felbamate, lamotrigine, topiramate, oxcarbazepine, lacosamide Antilipidemic agents Atorvastatin, fluvastatin, simvastatin Antiplatelets Ticagrelor Antiviral agents Efavirenz, lopinavir/ritonavir, indinavir, nelfinavir, ritonavir, saquinavir Fosamprenavir: phenytoin when given with fosamprenavir alone may decrease the concentration of amprenavir, the active metabolite. 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.

Fosamprenavir/ritonavir produces little or no change in rosuvastatin exposure. Caution should be exercised when coadministered.

HIV-1 protease inhibitor producing little or no change in rosuvastatin exposure. Caution should be exercised when coadministered.

The recommended dose of BELSOMRA is 5 mg in subjects receiving moderate CYP3A inhibitors (e.g., amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil).

Using cross-study comparisons to historical pharmacokinetic data for each interacting drug, dolutegravir did not appear to affect the pharmacokinetics of the following drugs: atazanavir, darunavir, efavirenz, etravirine, fosamprenavir, lopinavir, ritonavir, and boceprevir. Protease inhibitor: Fosamprenavir/ritonavir a Tipranavir/ritonavir a ↓Dolutegravir In adults and in pediatric patients weighing at least 25 kg , adjust dolutegravir dose to 50 mg twice daily.

This table includes potentially significant interactions, but is not all inclusive Table 5: Established and Other Potentially Significant Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction Concomitant Drug Class: Drug Name Effect Clinical Comment HIV antiviral agents Protease inhibitor: Fosamprenavir calcium ↓ amprenavir Fosamprenavir (unboosted): Appropriate doses of the combinations with respect to safety and efficacy have not been established. Fosamprenavir/ritonavir: An additional 100 mg/day (300 mg total) of ritonavir is recommended when efavirenz tablets are administered with fosamprenavir/ritonavir once daily. No change in the ritonavir dose is required when efavirenz tablets are administered with fosamprenavir plus ritonavir twice daily.

Protease inhibitor: fosamprenavir calcium ↓ amprenavir Fosamprenavir (unboosted): Appropriate doses of fosamprenavir and efavirenz, emtricitabine and tenofovir disoproxil fumarate with respect to safety and efficacy have not been established. Fosamprenavir/ritonavir: An additional 100 mg/day (300 mg total) of ritonavir is recommended when efavirenz, emtricitabine and tenofovir disoproxil fumarate is administered with fosamprenavir/ritonavir once daily. No change in the ritonavir dose is required when efavirenz, emtricitabine and tenofovir disoproxil fumarate is administered with fosamprenavir plus ritonavir twice daily.

HIV-antiviral agents: protease inhibitors (PIs) atazanavir (without ritonavir) atazanavir/ritonavir atazanavir/cobicistat darunavir/ritonavir darunavir/cobicistat fosamprenavir (without ritonavir) fosamprenavir/ritonavir indinavir (without ritonavir) lopinavir/ritonavir ↓ atazanavir ↓ atazanavir ↔ etravirine ↓ atazanavir ↓ cobicistat ↓ etravirine ↓ cobicistat darunavir: effect unknown ↑ amprenavir ↑ amprenavir ↓ indinavir ↓ etravirine Co-administration of etravirine tablets and atazanavir without low- dose ritonavir is not recommended. Concomitant use of etravirine tablets with fosamprenavir without low-dose ritonavir may cause a significant alteration in the plasma concentration of amprenavir. Co-administration of etravirine tablets and fosamprenavir without low-dose ritonavir is not recommended.

7 DRUG INTERACTIONS Coadministration of fosamprenavir calcium with drugs that induce CYP3A4 may decrease amprenavir (active metabolite) concentrations leading to potential loss of virologic activity. (7, 12.3) Coadministration of fosamprenavir calcium or fosamprenavir calcium and ritonavir may result in clinically significant interactions with drugs metabolized by CYP3A4. (7) Coadministration of fosamprenavir calcium and ritonavir may result in clinically significant interactions with drugs metabolized by CYP2D6.

Intervention Concomitant administration of ibuprofen and famotidine tablet is not recommended with dasatinib, delavirdine mesylate, cefditoren, and fosamprenavir.

Examples Antivirals (e.g., ritonavir, ritonavir-boosted darunavir, ritonavir-boosted fosamprenavir, saquinavir) Glucocorticoid and progesterone receptor antagonists (e.g., mifepristone) Strong CYP3A4 Inducers Clinical Impact May decrease plasma concentrations of levoketoconazole and reduce the efficacy of RECORLEV Prevention or Management Administration of strong enzyme inducers of CYP3A4 with RECORLEV is not recommended.

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.

Fosamprenavir/Ritonavir Clinical Impact Co-administration of fosamprenavir/ritonavir with paroxetine significantly decreased plasma levels of paroxetine.

Fosamprenavir/Ritonavir Co-administration of fosamprenavir/ritonavir with paroxetine significantly decreased plasma levels of paroxetine.

Other boosted PIs (atazanavir/ritonavir, fosamprenavir/ritonavir, saquinavir/ritonavir, tipranavir/ritonavir) ↑ rilpivirine ↔ boosted PI Concomitant use of rilpivirine tablets with boosted PIs may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). Unboosted PIs (atazanavir, fosamprenavir, indinavir, nelfinavir) ↑ rilpivirine ↔ unboosted PI Concomitant use of rilpivirine tablets with unboosted PIs may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes).

Other boosted PIs (atazanavir/ritonavir, fosamprenavir/ritonavir, saquinavir/ritonavir, tipranavir/ritonavir) ↑ rilpivirine ↔ boosted PI Concomitant use of EDURANT or EDURANT PED with boosted PIs may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). Unboosted PIs (atazanavir, fosamprenavir, indinavir, nelfinavir) ↑ rilpivirine ↔ unboosted PI Concomitant use of EDURANT or EDURANT PED with unboosted PIs may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes).

Protease Inhibitors (co-administered with 200 mg of ritonavir): Fosamprenavir ↓ Amprenavir Combining a protease inhibitor with APTIVUS/ritonavir is not recommended.

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.

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 .