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
Other HMG-CoA reductase inhibitors: e.g., atorvastatin rosuvastatin ↑ HMG-CoA reductase inhibitors Coadministration of atazanavir and TYBOST with atorvastatin is not recommended. Dosage recommendations with atorvastatin or rosuvastatin are as follows. TYBOST coadministered with atazanavir in adult patients: Rosuvastatin dosage should not exceed 10 mg TYBOST coadministered with darunavir in adult patients: Atorvastatin dosage should not exceed 20 mg Rosuvastatin dosage should not exceed 20 mg Other lipid-modifying agents: lomitapide ↑ lomitapide Coadministration with lomitapide is contraindicated due to potential for markedly increased transaminases.
Source: FDA drug label - cobicistat
Lipid Modifying Agents: HMG-CoA reductase inhibitors : lovastatin, simvastatin atorvastatin, pravastatin, rosuvastatin Other lipid modifying agents: lomitapide ↑ lovastatin ↑ simvastatin ↑ HMG-CoA reductase inhibitors ↑ lomitapide Co-administration is contraindicated due to potential for serious reactions such as myopathy including rhabdomyolysis. Titrate atorvastatin, pravastatin or rosuvastatin dose carefully and use the lowest necessary dose while monitoring for adverse events. Do not exceed atorvastatin 20 mg/day.
Source: FDA drug label - darunavir 600 mg
atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin ↑ atorvastatin ↑ fluvastatin ↑ pravastatin ↑ rosuvastatin pitavastatin: effect unknown For atorvastatin, fluvastatin, pitavastatin, pravastatin, and rosuvastatin, start with the lowest recommended dose and titrate while monitoring for safety (e.g. Dosage recommendations with atorvastatin or rosuvastatin are as follows: atorvastatin dosage should not exceed 20 mg/day rosuvastatin dosage should not exceed 20 mg/day Other lipid modifying agents: lomitapide ↑ lomitapide Co-administration is contraindicated due to potential for markedly increased transaminases associated with increased plasma concentrations of lomitapide.
Source: FDA drug label - darunavir ethanolate and cobicistat
HMG-CoA Reductase Inhibitors: Lovastatin Simvastatin Contraindicated Lovastatin, Simvastatin, Atorvastatin, Pravastatin, Fluvastatin : (see CONTRAINDICATIONS , WARNINGS ). Atorvastatin Pravastatin Use With Caution Fluvastatin No Dose Adjustment Hypoglycemic Agents: Nateglinide Pioglitazone Repaglinide Rosiglitazone Use With Caution Nateglinide, Pioglitazone, Repaglinide, Rosiglitazone: (see WARNINGS , ADVERSE REACTIONS ).
Source: FDA drug label - lansoprazole, amoxicillin, clarithromycin
7 DRUG INTERACTIONS Consult approved product labeling for drugs that are substrates of CYP3A4, P-gp, OCT2, and MATE prior to initiating RECORLEV ( 7.1 ) Sensitive CYP3A4 or CYP3A4 and P-gp Substrates : Concomitant use of RECORLEV with these substrates is contraindicated or not recommended ( 7.1 ) Atorvastatin : Use lowest atorvastatin dose possible and monitor for adverse reactions for dosages exceeding 20 mg daily ( 7.1 ) Metformin : Monitor glycemia, kidney function, and vitamin B12 and adjust metformin dosage as needed ( 7.1 ) Strong CYP3A4 Inhibitors or Inducers : Avoid use of these drugs 2 weeks before and during RECORLEV treatment ( 7.2 ) Gastric Acid Modulators : See Full Prescribing Information for recommendations regarding concomitant use with RECORLEV ( 7.2 ) 7.1 Effect of RECORLEV on Other Drugs Levoketoconazole is a strong CYP3A4 inhibitor, as well as an inhibitor of the drug transporters P-gp, OCT2, and MATE1 in vivo. It also includes the clinical impact and management recommendations for concomitant use of RECORLEV with atorvastatin and metformin. CYP3A4 Substrate Atorvastatin c Clinical Impact Increases plasma concentration of atorvastatin c and may increase the risk of atorvastatin-associated myopathy and rhabdomyolysis [see Clinical Pharmacology ( 12.3 )] .
Source: FDA drug label - levoketoconazole
Prevention or Management HMG CoA reductase inhibitors (“Statins”) Coadministration of ZOKINVY with lovastatin, simvastatin, or atorvastatin is contraindicated [see Contraindications ( 4 )] . As noted above, use with lovastatin, simvastatin, or atorvastatin, and midazolam is contraindicated [see Contraindications ( 4 )] ).
Source: FDA drug label - lonafarnib
Lipid-modifying agents HMG-CoA Reductase Inhibitors: lovastatin simvastatin atorvastatin rosuvastatin Microsomal triglyceride transfer protein (MTTP) Inhibitor: lomitapide ↑ lovastatin ↑ simvastatin ↑ atorvastatin ↑ rosuvastatin ↑ lomitapide Contraindicated due to potential for myopathy including rhabdomyolysis [see Contraindications (4)]. Use atorvastatin with caution and at the lowest necessary dose.
Source: FDA drug label - lopinavir and ritonavir
Prevention or Management Atorvastatin, Lovastatin, Simvastatin Concomitant use with posaconazole is contraindicated.
Source: FDA drug label - posaconazole
Proton Pump Inhibitors: e.g., esomeprazole lansoprazole omeprazole pantoprazole rabeprazole ↓ rilpivirine Coadministration is contraindicated with rilpivirine tablets [see Contraindications (4) ] In addition to the drugs included in Table 6, the interaction between rilpivirine tablets and the following drugs was evaluated in clinical studies and no dose adjustment is needed for either drug [see Clinical Pharmacology ( 12.3 )] : acetaminophen, atorvastatin, chlorzoxazone, cabotegravir, ethinylestradiol, norethindrone, raltegravir, sildenafil, simeprevir and tenofovir disoproxil fumarate.
Source: FDA drug label - rilpivirine
Lipid-modifying agents HMG-CoA Reductase Inhibitor: lovastatin simvastatin atorvastatin rosuvastatin Microsomal triglyceride transfer protein (MTTP) Inhibitor: lomitapide ↑ lovastatin ↑ simvastatin ↑ atorvastatin ↑ rosuvastatin ↑ lomitapide Contraindicated due to potential for myopathy including rhabdomyolysis [see Contraindications (4) ]. Titrate atorvastatin and rosuvastatin dose carefully and use the lowest necessary dose. If ritonavir is used with another protease inhibitor, see the complete prescribing information for the concomitant protease inhibitor for details on co- administration with atorvastatin and rosuvastatin.
Source: FDA drug label - ritonavir
Lipid-modifying agents HMG-CoA Reductase Inhibitor: lovastatin simvastatin atorvastatin rosuvastatin Microsomal triglyceride transfer protein (MTTP) Inhibitor: lomitapide ↑ lovastatin ↑ simvastatin ↑ atorvastatin ↑ rosuvastatin ↑ lomitapide Contraindicated due to potential for myopathy including rhabdomyolysis [see Contraindications ( 4 )] . Titrate atorvastatin and rosuvastatin dose carefully and use the lowest necessary dose. If ritonavir is used with another protease inhibitor, see the complete prescribing information for the concomitant protease inhibitor for details on co-administration with atorvastatin and rosuvastatin.
Source: FDA drug label - ritonavir 100 mg
Other Potentially Significant Drug Interactions Concomitant Drug Class or Food Noted or Anticipated Outcome Clinical Comment HMG-CoA Reductase Inhibitors: atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin Pharmacokinetic and/or pharmacodynamic interaction: the addition of one drug to a stable long-term regimen of the other has resulted in myopathy and rhabdomyolysis (including a fatality) Weigh the potential benefits and risks and carefully monitor patients for any signs or symptoms of muscle pain, tenderness, or weakness, particularly during initial therapy; monitoring CPK (creatine phosphokinase) will not necessarily prevent the occurrence of severe myopathy.
Source: FDA drug label - colchicine
HMG-CoA Reductase Inhibitors: Atorvastatin Rosuvastatin ↑ Atorvastatin ↓ Hydroxy-atorvastatin metabolites ↑ Rosuvastatin Avoid co-administration with atorvastatin.
Source: FDA drug label - tipranavir
7.2 Transporters Use caution when concomitantly administering eltrombopag and drugs that are substrates of OATP1B1 (e.g., atorvastatin, bosentan, ezetimibe, fluvastatin, glyburide, olmesartan, pitavastatin, pravastatin, rosuvastatin, repaglinide, rifampin, simvastatin acid, SN-38 [active metabolite of irinotecan], valsartan) or breast cancer resistance protein (BCRP) (e.g., imatinib, irinotecan, lapatinib, methotrexate, mitoxantrone, rosuvastatin, sulfasalazine, topotecan).
Source: FDA drug label - eltrombopag
7.2 Transporters Use caution when concomitantly administering PROMACTA and drugs that are substrates of OATP1B1 (e.g., atorvastatin, bosentan, ezetimibe, fluvastatin, glyburide, olmesartan, pitavastatin, pravastatin, rosuvastatin, repaglinide, rifampin, simvastatin acid, SN-38 [active metabolite of irinotecan], valsartan) or breast cancer resistance protein (BCRP) (e.g., imatinib, irinotecan, lapatinib, methotrexate, mitoxantrone, rosuvastatin, sulfasalazine, topotecan).
Source: FDA drug label - eltrombopag olamine
Statins: Rosuvastatin b Atorvastatin Fluvastatin Pitavastatin Simvastatin ↑Rosuvastatin ↑Atorvastatin ↑Fluvastatin ↑Pitavastatin ↑Simvastatin Use the lowest possible starting dose for statins and monitor for statin-associated adverse events.
Source: FDA drug label - fostemsavir tromethamine
atorvastatin ↑ atorvastatin Coadministration of HARVONI with atorvastatin may be associated with increased risk of myopathy, including rhabdomyolysis.
Source: FDA drug label - ledipasvir and sofosbuvir
For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking leflunomide [see Clinical Pharmacology (12.3) ].
Source: FDA drug label - leflunomide
For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG- Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking leflunomide tablets [see Clinical Pharmacology (12.3)].
Source: FDA drug label - leflunomide and diclofenac sodium gel
HMG-CoA Reductase Inhibitors – When single 40 mg doses of simvastatin or atorvastatin, both substrates of CYP3A4, were given to healthy adult volunteers who had received nefazodone hydrochloride, 200 mg BID for 6 days, approximately 20 fold increases in plasma concentrations of simvastatin and simvastatin acid and 3 to 4 fold increases in plasma concentrations of atorvastatin and atorvastatin lactone were seen. Caution should be used if nefazodone is administered in combination with HMG-CoA reductase inhibitors that are metabolized by CYP3A4, such as simvastatin, atorvastatin, and lovastatin, and dosage adjustments of these HMG-CoA reductase inhibitors are recommended. This is consistent with the interactions observed between nefazodone and triazolam, alprazolam, buspirone, atorvastatin, and simvastatin, drugs metabolized by this isozyme.
Source: FDA drug label - nefazodone hydrochloride
Exercise caution when co-administering KEVZARA with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc.
Source: FDA drug label - sarilumab
Exercise caution when SYLVANT is co-administered with CYP3A4 substrate drugs where a decrease in effectiveness would be undesirable (e.g., oral contraceptives, lovastatin, atorvastatin).
Source: FDA drug label - siltuximab
For other substrates of BCRP (e.g., mitoxantrone) and drugs in the OATP family (e.g., methotrexate, rifampin), especially HMG-Co reductase inhibitors (e.g., atorvastatin, nateglinide, pravastatin, repaglinide, and simvastatin), consider reducing the dose of these drugs and monitor patients closely for signs and symptoms of increased exposures to the drugs while patients are taking teriflunomide tablets [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - teriflunomide
Exercise caution when coadministering TOFIDENCE with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc.
Source: FDA drug label - tocilizumab
Exercise caution when coadministering TYENNE with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc.
Source: FDA drug label - tocilizumab-aazg
atorvastatin ↑ atorvastatin Coadministration of EPCLUSA with atorvastatin may be associated with increased risk of myopathy, including rhabdomyolysis.
Source: FDA drug label - velpatasvir and sofosbuvir
Lovastatin Simvastatin Atorvastatin Use VOQUEZNA TRIPLE PAK with caution. In situations where the concomitant use of VOQUEZNA TRIPLE PAK with atorvastatin or pravastatin cannot be avoided, atorvastatin dose should not exceed 20 mg daily and pravastatin dose should not exceed 40 mg daily.
Source: FDA drug label - vonoprazan fumarate and amoxicillin
HMG-CoA Reductase Inhibitors simvastatin, lovastatin, atorvastatin Increased plasma concentration of HMG-CoA reductase inhibitor.
Source: FDA drug label - amiodarone hydrochloride
7 DRUG INTERACTIONS Data from a drug-drug interaction study involving 10 mg of amlodipine and 80 mg of atorvastatin in healthy subjects indicate that the pharmacokinetics of amlodipine are not altered when the drugs are co-administered. The effect of amlodipine on the pharmacokinetics of atorvastatin showed no effect on the C max : 91% (90% confidence interval: 80 to 103%), but the AUC of atorvastatin increased by 18% (90% confidence interval: 109 to 127%) in the presence of amlodipine, which is not clinically meaningful. No drug interaction studies have been conducted with amlodipine and atorvastatin and other drugs, although studies have been conducted in the individual amlodipine and atorvastatin components, as described below: Amlodipine See full prescribing information for details regarding concomitant use of amlodipine and atorvastatin tablets with other drugs or grapefruit juice that increase the risk of myopathy and rhabdomyolysis (2.5, 7.3 ).
Source: FDA drug label - amlodipine and atorvastatin
Impact of Amlodipine on Other Drugs Coadministered amlodipine does not affect the exposure to atorvastatin, digoxin, ethanol and the warfarin prothrombin response time.
Source: FDA drug label - amlodipine and valsartan
7.6 Atorvastatin Co-administration of multiple 10 mg doses of amlodipine with 80 mg of atorvastatin resulted in no significant change in the steady-state pharmacokinetic parameters of atorvastatin.
Source: FDA drug label - amlodipine besylate
atorvastatin, rosuvastatin ↑ atorvastatin ↑ rosuvastatin Titrate atorvastatin dose carefully and use the lowest necessary dose.
Source: FDA drug label - atazanavir
Other HMG-CoA reductase inhibitors: atorvastatin, fluvastatin, pravastatin, rosuvastatin ↑ HMG-CoA reductase inhibitors Coadministration of EVOTAZ with atorvastatin is not recommended.
Source: FDA drug label - atazanavir and cobicistat
atorvastatin, rosuvastatin ↑ atorvastatin ↑ rosuvastatin Titrate atorvastatin dose carefully and use the lowest necessary dose.
Source: FDA drug label - atazanavir sulfate
• Rifampin: May reduce atorvastatin plasma concentrations. 7.1 Drug Interactions that may Increase the Risk of Myopathy and Rhabdomyolysis with ATORVALIQ Atorvastatin is a substrate of CYP3A4 and transporters (e.g., OATP1B1/1B3, P-gp, or BCRP). Atorvastatin plasma levels can be significantly increased with concomitant administration of inhibitors of CYP3A4 and transporters.
Source: FDA drug label - atorvaliq
7 DRUG INTERACTIONS See full prescribing information for details regarding concomitant use of atorvastatin calcium with other drugs or grapefruit juice that increase the risk of myopathy and rhabdomyolysis ( 2.5 , 7.1 ). Rifampin: May reduce atorvastatin plasma concentrations. Administer simultaneously with atorvastatin calcium ( 7.2 ).
Source: FDA drug label - atorvastatin calcium
Atorvastatin: Bexarotene concentrations were not affected by concomitant atorvastatin administration. Atorvastatin: The exposure (AUC) to atorvastatin (a substrate for CYP3A4) decreased by half when atorvastatin was co-administered with bexarotene capsules (400 mg/m 2 orally once daily).
Source: FDA drug label - bexarotene
Rilpivirine Based on drug interaction study results, the following drugs can be coadministered with rilpivirine (non-antiretrovirals and cabotegravir) or given after discontinuation of rilpivirine (antiretrovirals and non-antiretrovirals): acetaminophen, atorvastatin, cabotegravir, chlorzoxazone, dolutegravir, ethinyl estradiol, norethindrone, raltegravir, ritonavir-boosted atazanavir, ritonavir-boosted darunavir, sildenafil, tenofovir alafenamide, and tenofovir disoproxil fumarate [see Clinical Pharmacology ( 12.3 )] .
Source: FDA drug label - cabotegravir and rilpivirine
7.3 Atorvastatin Concomitant administration of bazedoxifene (40 mg daily) and atorvastatin (20 mg, single-dose) to healthy postmenopausal women did not affect the pharmacokinetics of bazedoxifene, atorvastatin or its active metabolites.
Source: FDA drug label - conjugated estrogens/bazedoxifene
HMG-CoA reductase inhibitors (statins) Literature and postmarketing cases of myotoxicity, including muscle pain and weakness, myositis, and rhabdomyolysis, have been reported with concomitant administration of cyclosporine with lovastatin, simvastatin, atorvastatin, pravastatin, and, rarely fluvastatin.
Source: FDA drug label - cyclosporine
Impact of Dabigatran on Other Drugs In clinical studies exploring CYP3A4, CYP2C9, P-gp and other pathways, dabigatran did not meaningfully alter the pharmacokinetics of amiodarone, atorvastatin, clarithromycin, diclofenac, clopidogrel, digoxin, pantoprazole, or ranitidine.
Source: FDA drug label - dabigatran etexilate
The risk of myopathy and rhabdomyolysis is increased by concomitant administration of danazol with statins such as simvastatin, atorvastatin and lovastatin.
Source: FDA drug label - danazol
atorvastatin, pravastatin, rosuvastatin ↑ HMG-CoA reductase inhibitors Co-administration of darunavir/ritonavir with HMG-CoA reductase inhibitors may lead to adverse events such as myopathy. Titrate atorvastatin, pravastatin or rosuvastatin dose carefully and use the lowest necessary dose while monitoring for adverse events. Do not exceed atorvastatin 20 mg/day.
Source: FDA drug label - darunavir
Substances increasing the plasma concentrations of COCs Co-administration of atorvastatin or rosuvastatin and certain COCs containing EE increase AUC values for EE by approximately 20 to 25%.
Source: FDA drug label - desogestrel and ethinyl estradiol
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
7.2 Effect of PIFELTRO on Other Drugs No clinically significant changes in concentration were observed for the following agents when co-administered with doravirine: dolutegravir, lamivudine, TDF, elbasvir and grazoprevir, ledipasvir and sofosbuvir, atorvastatin, an oral contraceptive containing ethinyl estradiol and levonorgestrel, metformin, methadone, and midazolam [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - doravirine
7.3 Effect of DELSTRIGO on Other Drugs No clinically significant changes in concentration were observed for the following agents when co-administered with doravirine: lamivudine, TDF, elbasvir and grazoprevir, ledipasvir and sofosbuvir, atorvastatin, an oral contraceptive containing ethinyl estradiol and levonorgestrel, metformin, methadone, or midazolam.
Source: FDA drug label - doravirine, lamivudine, and tenofovir disoproxil fumarate
Substances increasing the plasma concentrations of COCs: Co-administration of atorvastatin and certain COCs containing EE increase AUC values for EE by approximately 20%. Substances increasing the plasma concentrations of COCs: Co-administration of atorvastatin and certain COCs containing EE increase AUC values for EE by approximately 20%.
Source: FDA drug label - drospirenone and ethinyl estradiol
Substances increasing the plasma concentrations of COCs: Co-administration of atorvastatin with certain COCs containing EE increase AUC values for EE by approximately 20%.
Source: FDA drug label - drospirenone, ethinyl estradiol and levomefolate calcium and levomefolate calcium
Substances increasing the plasma concentrations of COCs: Co-administration of atorvastatin and certain COCs containing EE increase AUC values for EE by approximately 20%.
Source: FDA drug label - drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
HMG-CoA reductase inhibitors: Atorvastatin Pravastatin Simvastatin ↓ atorvastatin * ↓ pravastatin * ↓ simvastatin * Plasma concentrations of atorvastatin, pravastatin, and simvastatin decreased.
Source: FDA drug label - efavirenz
HMG-CoA reductase inhibitors: atorvastatin pravastatin simvastatin ↓ atorvastatin ↓ pravastatin ↓ simvastatin Plasma concentrations of atorvastatin, pravastatin, and simvastatin decreased with EFV.
Source: FDA drug label - efavirenz, emtricitabine and tenofovir disoproxil fumarate
HMG-CoA reductase inhibitors: Atorvastatin Pravastatin Simvastatin ↓atorvastatin* ↓pravastatin* ↓simvastatin* Plasma concentrations of atorvastatin, pravastatin, and simvastatin decreased.
Source: FDA drug label - efavirenz, lamivudine and tenofovir disoproxil fumarate
: Atorvastatin ↑ atorvastatin The dose of atorvastatin should not exceed a daily dose of 20 mg when co-administered with ZEPATIER.
Source: FDA drug label - elbasvir and grazoprevir
atorvastatin ↑ atorvastatin Initiate atorvastatin with the lowest starting dose of atorvastatin and titrate carefully while monitoring for safety (e.g., myopathy). Do not exceed a dosage of atorvastatin 20 mg daily.
Source: FDA drug label - elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide
No clinically significant drug interactions have been observed between RPV and the following medications: acetaminophen, atorvastatin, chlorzoxazone, ethinyl estradiol, ledipasvir/sofosbuvir, norethindrone, sildenafil, simeprevir, sofosbuvir, sofosbuvir/velpatasvir, sofosbuvir/velpatasvir/voxilaprevir, or TDF.
Source: FDA drug label - emtricitabine, rilpivirine and tenofovir disoproxil fumarate
7.8 Drugs Without Clinically Significant Interactions with ODEFSEY Based on drug interaction studies conducted with the fixed dose combination or components of ODEFSEY, no clinically significant drug interactions have been observed when ODEFSEY is combined with the following drugs: acetaminophen, atorvastatin, chlorzoxazone, digoxin, ethinyl estradiol, ledipasvir, metformin, midazolam, norethindrone, norgestimate, sildenafil, simeprevir, sofosbuvir, velpatasvir, and voxilaprevir.
Source: FDA drug label - emtricitabine, rilpivirine hydrochloride, and tenofovir alafenamide
No clinically significant drug interactions have been observed between RPV and the following medications: acetaminophen, atorvastatin, chlorzoxazone, ethinyl estradiol, ledipasvir/sofosbuvir, norethindrone, sildenafil, simeprevir, sofosbuvir, sofosbuvir/velpatasvir, sofosbuvir/velpatasvir/voxilaprevir, or TDF.
Source: FDA drug label - emtricitabine, rilpivirine, tenofovir disoproxil fumarate
These include colchicine toxicity with colchicine; rhabdomyolysis with simvastatin, lovastatin and atorvastatin; and hypotension with calcium channel blockers metabolized by CYP3A4 (e.g., verapamil, amlodipine, diltiazem) (see PRECAUTIONS - Drug Interactions ).
Source: FDA drug label - erythromycin
Substances increasing the plasma concentrations of CHCs Co-administration of atorvastatin and certain CHCs containing ethinyl estradiol increase AUC values for ethinyl estradiol by approximately 20-25%.
Source: FDA drug label - etonogestrel and ethinyl estradiol
Substances increasing the plasma concentrations of CHCs Co-administration of atorvastatin and certain CHCs containing ethinyl estradiol increase AUC values for ethinyl estradiol by approximately 20-25%.
Source: FDA drug label - etonogestrel and ethinyl estradiol vaginal
HMG-CoA reductase inhibitors : atorvastatin ↔ etravirine ↓ atorvastatin ↑ 2-OH-atorvastatin The combination of etravirine tablets and atorvastatin can be given without dose adjustments, however, the dose of atorvastatin may need to be altered based on clinical response. HMG-CoA reductase inhibitors : atorvastatin ↔ etravirine ↓ atorvastatin ↑ 2-OH-atorvastatin The combination of etravirine tablets and atorvastatin can be given without dose adjustments, however, the dose of atorvastatin may need to be altered based on clinical response.
Source: FDA drug label - etravirine
7.6 Atorvastatin (CYP3A4 Substrate) and Pravastatin (P-gp Substrate) Single-dose administration of everolimus with either atorvastatin or pravastatin to healthy subjects did not influence the pharmacokinetics of atorvastatin, pravastatin and everolimus, as well as total HMG-CoA reductase bioreactivity in plasma to a clinically relevant extent.
Source: FDA drug label - everolimus
7.6 Atorvastatin (CYP3A4 Substrate) and Pravastatin (P-gp Substrate) Single-dose administration of everolimus with either atorvastatin or pravastatin to healthy subjects did not influence the pharmacokinetics of atorvastatin, pravastatin and everolimus, as well as total HMG-CoA reductase bioreactivity in plasma to a clinically relevant extent.
Source: FDA drug label - everolimus tablets
7 DRUG INTERACTIONS Table 2: Oral drugs that can be administered concomitantly with ferric citrate Amlodipine Aspirin Atorvastatin Calcitriol Clopidogrel Digoxin Diltiazem Doxercalciferol Enalapril Fluvastatin Glimepiride Levofloxacin Losartan Metoprolol Pravastatin Propranolol Sitagliptin Warfarin Oral drugs that have to be separated from ferric citrate and meals Dosing Recommendations Doxycycline Take at least 1 hour before ferric citrate Ciprofloxacin Take at least 2 hours before or after ferric citrate Oral medications not listed in Table 2.
Source: FDA drug label - ferric citrate
HMG-CoA reductase inhibitors : The risk of myopathy and rhabdomyolysis increases when fluconazole is coadministered with HMG-CoA reductase inhibitors metabolized through CYP3A4, such as atorvastatin and simvastatin, or through CYP2C9, such as fluvastatin.
Source: FDA drug label - fluconazole
Lipid Modifying Agents: HMG-CoA reductase inhibitors : Atorvastatin a Lovastatin, simvastatin Other lipid modifying agents : Lomitapide ↑Atorvastatin ↑Lovastatin ↑Simvastatin ↑Lomitapide Titrate atorvastatin dose carefully and use the lowest necessary dose; do not exceed atorvastatin 20 mg/day.
Source: FDA drug label - fosamprenavir calcium
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.
Source: FDA drug label - fosphenytoin sodium
(D) OATP1B1 substrates: Gemfibrozil is an inhibitor of OATP1B1 transporter and may increase exposure of drugs that are substrates of OATP1B1 (e.g., atrasentan, atorvastatin, bosentan, ezetimibe, fluvastatin, glyburide, SN-38 [active metabolite of irinotecan], rosuvastatin, pitavastatin, pravastatin, rifampin, valsartan, olmesartan).
Source: FDA drug label - gemfibrozil
HMG-CoA Reductase Inhibitors: Atorvastatin Lovastatin Simvastatin ↑ atorvastatin ↑ lovastatin ↑ simvastatin Coadministration may increase the concentration of atorvastatin, lovastatin, and simvastatin.
Source: FDA drug label - glecaprevir and pibrentasvir
7.2 Effect of NOURIANZ on Other Drugs CYP3A4 Substrates Coadministration of NOURIANZ 20 mg with a CYP3A4 substrate (midazolam) did not affect the CYP3A4 substrate exposure, while concomitant administration of NOURIANZ 40 mg increased the CYP3A4 substrate (atorvastatin) C max and AUC inf by 1.5-fold [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - istradefylline
Immunosuppres sants everolimus, temsirolimus budesonide, ciclesonide, cyclosporine, dexamethasone, fluticasone, methylprednisolone, rapamycin (also known as sirolimus), tacrolimus Lipid Regulating Drugs lovastatin, simvastatin atorvastatin The potential increase in plasma concentrations of atorvastatin, lovastatin, and simvastatin when coadministered with itraconazole may increase the risk of skeletal muscle toxicity, including rhabdomyolysis.
Source: FDA drug label - itraconazole
Lipid Regulating Drugs lovastatin, simvastatin atorvastatin The potential increase in plasma concentrations of atorvastatin, lovastatin and simvastatin when coadministered with ketoconazole tablets may increase the risk of skeletal Muscle toxicity, including rhabdomyolysis.
Source: FDA drug label - ketoconazole
7.3 Drugs without Clinically Significant Interactions with YEZTUGO Based on drug interaction studies conducted with YEZTUGO, no clinically significant drug interactions have been observed with: atorvastatin, famotidine, pitavastatin, rosuvastatin, tenofovir alafenamide, and voriconazole.
Source: FDA drug label - lenacapavir sodium
HMG-CoA Reductase Inhibitors atorvastatin ↑ atorvastatin When PREVYMIS is co-administered with atorvastatin, do not exceed an atorvastatin dosage of 20 mg daily . When PREVYMIS is co-administered with cyclosporine, use of atorvastatin is not recommended.
Source: FDA drug label - letermovir
Substances increasing the systemic exposure of COCs: Co-administration of atorvastatin or rosuvastatin and certain COCs containing ethinyl estradiol (EE) increase AUC values for EE by approximately 20 to 25%.
Source: FDA drug label - levonorgestrel and ethinyl estradiol
Substances Increasing the Plasma Concentrations of COCs Co-administration of atorvastatin or rosuvastatin and certain COCs containing EE increase AUC values for EE by approximately 20 to 25%.
Source: FDA drug label - levonorgestrel and ethinyl estradiol and ethinyl estradiol tablets
Substances increasing the plasma concentrations of COCs: Co-administration of atorvastatin or rosuvastatin and certain COCs containing EE increase AUC values for EE by approximately 20 to 25%.
Source: FDA drug label - levonorgestrel and ethinyl estradiol and ferrous fumarate
7.2 Weak CYP3A4 Inhibitors Weak CYP3A4 inhibitors (such as alprazolam, amiodarone, amlodipine, atorvastatin, bicalutamide, cilostazol, cimetidine, cyclosporine, fluoxetine, fluvoxamine, ginkgo, goldenseal, isoniazid, lapatinib, nilotinib, pazopanib, ranitidine, ranolazine, ticagrelor, zileuton) can increase lomitapide exposure approximately 2-fold [see Clinical Pharmacology (12.3) ] .
Source: FDA drug label - lomitapide mesylate
HMG-CoA REDUCTASE INHIBITORS Atorvastatin Rosuvastatin ↑ atorvastatin ↑ rosuvastatin Titrate atorvastatin dose carefully and use the lowest necessary dose; do not exceed atorvastatin 40 mg/day.
Source: FDA drug label - nelfinavir mesylate
Lower starting and maintenance doses of other CYP3A4 substrates (e.g., atorvastatin) may be required as amiodarone may increase the plasma concentration of these drugs.
Source: FDA drug label - nexterone (amiodarone hci)
HMG-CoA reductase inhibitors atorvastatin ↑ atorvastatin Consider temporary discontinuation of atorvastatin during treatment with PAXLOVID. Atorvastatin does not need to be withheld prior to or after completing PAXLOVID.
Source: FDA drug label - nirmatrelvir and ritonavir
Substances Increasing the Plasma Concentrations of CHCs Co-administration of atorvastatin or rosuvastatin and certain CHCs containing EE increase AUC values for EE by approximately 20% to 25%.
Source: FDA drug label - norelgestromin and ethinyl estradiol
Substances increasing the plasma concentrations of COCs: Co-administration of atorvastatin and certain COCs containing ethinyl estradiol increase AUC values for ethinyl estradiol by approximately 20%.
Source: FDA drug label - norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets
Substances Increasing the Plasma Concentrations of COCs Co-administration of atorvastatin or rosuvastatin and certain COCs containing ethinyl estradiol (EE) increase AUC values for EE by approximately 20 to 25%.
Source: FDA drug label - norethindrone acetate/ethinyl estradiol
Substances increasing the plasma concentrations of COCs Co-administration of atorvastatin or rosuvastatin and certain COCs containing EE increase AUC values for EE by approximately 20-25%.
Source: FDA drug label - norethindrone and ethinyl estradiol
Substances increasing the plasma concentrations of COCs Coadministration of atorvastatin or rosuvastatin and certain COCs containing ethinyl estradiol (EE) increase AUC values for EE by approximately 20 to 25%.
Source: FDA drug label - norgestimate and ethinyl estradiol
Table 3: No observed clinically important drug interactions of Veltassa Angiotensin-converting enzyme (ACE) inhibitors Benazepril, captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril Angiotensin II receptor blockers (ARB) Azilsartan, candesartan, irbesartan, losartan, olmesartan, valsartan β-adrenoceptor blockers (β-blocker) Metoprolol Loop diuretics Furosemide, bumetanide, torasemide Mineralocorticoid receptor antagonists (MRA) Eplerenone, finerenone, spironolactone Neprilysin inhibitors Sacubitril Sodium-glucose cotransporter-2 (SGLT-2) inhibitors Canagliflozin, dapagliflozin, empagliflozin Antibiotics Trimethoprim, amoxicillin, cephalexin Anticoagulants Warfarin, apixaban, rivaroxaban Anti-parathyroid agents and Thyroid preparations Cinacalcet Antithrombotic agents Clopidogrel, acetylsalicylic acid Blood glucose lowering drugs Glipizide Calcium channel blockers Amlodipine, verapamil Immunosuppressants Tacrolimus Others Lithium, allopurinol, atorvastatin, digoxin, phenytoin, riboflavin, sevelamer
Source: FDA drug label - patiromer
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, lacosamide, lamotrigine, topiramate, oxcarbazepine 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.
Source: FDA drug label - phenytoin
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 Antiepileptic drugs a Carbamazepine, felbamate, lamotrigine, topiramate, oxcarbazepine 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.
Source: FDA drug label - phenytoin sodium
Statins Atorvastatin (80 mg daily), a drug metabolized by CYP450 3A4, did not alter the pharmacokinetics of prasugrel’s active metabolite or its inhibition of platelet aggregation [see Drug Interactions (7.4) ] .
Source: FDA drug label - prasugrel
• Co-administration of multiple 10 mg doses of atorvastatin with 80 mg of quinapril resulted in no significant change in the steady-state pharmacokinetic parameters of atorvastatin.
Source: FDA drug label - quinapril
• Co-administration of multiple 10 mg doses of atorvastatin with 80 mg of quinapril hydrochloride resulted in no significant change in the steady-state pharmacokinetic parameters of atorvastatin.
Source: FDA drug label - quinapril hydrochloride
Atorvastatin (CYP3A4 Substrate) Rhabdomyolysis with acute renal failure secondary to myoglobinuria was reported in a patient taking atorvastatin administered with a single dose of quinine. Quinine may increase plasma concentrations of atorvastatin, thereby increasing the risk of myopathy or rhabdomyolysis. Thus, clinicians considering combined therapy of quinine sulfate with atorvastatin or other HMG-CoA reductase inhibitors ("statins") that are CYP3A4 substrates (e.g., simvastatin, lovastatin) should carefully weigh the potential benefits and risks of each medication.
Source: FDA drug label - quinine sulfate
methotrexate, fluvastatin, atorvastatin).
Source: FDA drug label - regorafenib
In addition to the drugs included in Table 6, the interaction between EDURANT and the following drugs was evaluated in clinical studies and no dose adjustment is needed for either drug [see Clinical Pharmacology (12.3) ] : acetaminophen, atorvastatin, chlorzoxazone, cabotegravir, ethinylestradiol, norethindrone, raltegravir, sildenafil, simeprevir and tenofovir disoproxil fumarate.
Source: FDA drug label - rilpivirine hydrochloride
However, there was an increase in systemic exposure to weak acids such as furosemide and atorvastatin, and a decrease in systemic exposure to weak bases such as dabigatran when co-administered with LOKELMA, as shown in Figure 2.
Source: FDA drug label - sodium zirconium cyclosilicate
atorvastatin fluvastatin lovastatin simvastatin ↑ atorvastatin ↑ fluvastatin ↑ lovastatin ↑ simvastatin Coadministration with VOSEVI may increase the concentrations of atorvastatin, fluvastatin, lovastatin, and simvastatin.
Source: FDA drug label - sofosbuvir, velpatasvir, and voxilaprevir
Amlodipine has no clinically relevant effects on the pharmacokinetics or pharmacodynamics of the following: atorvastatin, digoxin, warfarin.
Source: FDA drug label - telmisartan and amlodipine
Lower starting and maintenance doses of other CYP3A4 substrates (e.g., atorvastatin) may be required as verapamil may increase the plasma concentration of these drugs.
Source: FDA drug label - verapamil 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
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