Drug Interaction Report
12 potential interactions and/or warnings found for the following 2 drugs:
- deutivacaftor / tezacaftor / vanzacaftor
- efavirenz / lamivudine / tenofovir disoproxil
Interactions between your drugs
efavirenz tezacaftor
Applies to: efavirenz / lamivudine / tenofovir disoproxil, deutivacaftor / tezacaftor / vanzacaftor
GENERALLY AVOID: Coadministration with potent or moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of vanzacaftor, tezacaftor, and deutivacaftor, drugs primarily metabolized by the isoenzyme. Physiologically based pharmacokinetic (PBPK) simulations suggest that coadministration with the potent CYP450 3A4 inducer rifampin may decrease vanzacaftor peak plasma concentration (Cmax) and systemic exposure (AUC) by 78% and 82%, respectively, and may decrease deutivacaftor Cmax and AUC by 80% and 90%, respectively. Similarly, the moderate CYP450 3A4 inducer efavirenz is predicted to decrease vanzacaftor Cmax and AUC by 65% and 69%, respectively; and may decrease deutivacaftor Cmax and AUC by 56% and 73%, respectively. No pharmacokinetic data are available for tezacaftor, but decreased exposures are expected according to prescribing information.
MANAGEMENT: Concomitant use of vanzacaftor, tezacaftor, and deutivacaftor containing medications with potent CYP450 3A4 inducers is not recommended.
References (1)
- (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
efavirenz vanzacaftor
Applies to: efavirenz / lamivudine / tenofovir disoproxil, deutivacaftor / tezacaftor / vanzacaftor
GENERALLY AVOID: Coadministration with potent or moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of vanzacaftor, tezacaftor, and deutivacaftor, drugs primarily metabolized by the isoenzyme. Physiologically based pharmacokinetic (PBPK) simulations suggest that coadministration with the potent CYP450 3A4 inducer rifampin may decrease vanzacaftor peak plasma concentration (Cmax) and systemic exposure (AUC) by 78% and 82%, respectively, and may decrease deutivacaftor Cmax and AUC by 80% and 90%, respectively. Similarly, the moderate CYP450 3A4 inducer efavirenz is predicted to decrease vanzacaftor Cmax and AUC by 65% and 69%, respectively; and may decrease deutivacaftor Cmax and AUC by 56% and 73%, respectively. No pharmacokinetic data are available for tezacaftor, but decreased exposures are expected according to prescribing information.
MANAGEMENT: Concomitant use of vanzacaftor, tezacaftor, and deutivacaftor containing medications with potent CYP450 3A4 inducers is not recommended.
References (1)
- (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
efavirenz deutivacaftor
Applies to: efavirenz / lamivudine / tenofovir disoproxil, deutivacaftor / tezacaftor / vanzacaftor
GENERALLY AVOID: Coadministration with potent or moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of vanzacaftor, tezacaftor, and deutivacaftor, drugs primarily metabolized by the isoenzyme. Physiologically based pharmacokinetic (PBPK) simulations suggest that coadministration with the potent CYP450 3A4 inducer rifampin may decrease vanzacaftor peak plasma concentration (Cmax) and systemic exposure (AUC) by 78% and 82%, respectively, and may decrease deutivacaftor Cmax and AUC by 80% and 90%, respectively. Similarly, the moderate CYP450 3A4 inducer efavirenz is predicted to decrease vanzacaftor Cmax and AUC by 65% and 69%, respectively; and may decrease deutivacaftor Cmax and AUC by 56% and 73%, respectively. No pharmacokinetic data are available for tezacaftor, but decreased exposures are expected according to prescribing information.
MANAGEMENT: Concomitant use of vanzacaftor, tezacaftor, and deutivacaftor containing medications with potent CYP450 3A4 inducers is not recommended.
References (1)
- (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
lamiVUDine efavirenz
Applies to: efavirenz / lamivudine / tenofovir disoproxil, efavirenz / lamivudine / tenofovir disoproxil
MONITOR: Coadministration of efavirenz with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Efavirenz has been associated with hepatotoxicity during postmarketing use. Among reported cases of hepatic failure, a few occurred in patients with no preexisting hepatic disease or other identifiable risk factors.
MANAGEMENT: The risk of hepatic injury should be considered when efavirenz is used in combination with other agents that are potentially hepatotoxic (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; other HIV reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Monitoring of liver function tests should occur before and during treatment, especially in patients with underlying hepatic disease (including hepatitis B or C coinfection) or marked transaminase elevations. The benefit of continued therapy with efavirenz should be considered against the unknown risks of significant liver toxicity in patients who develop persistent elevations of serum transaminases greater than five times the upper limit of normal.
References (2)
- (2001) "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals
- Elsharkawy AM, Schwab U, McCarron B, et al. (2013) "Efavirenz induced acute liver failure requiring liver transplantation in a slow drug metaboliser." J Clin Virol, 58, p. 331-3
efavirenz tenofovir
Applies to: efavirenz / lamivudine / tenofovir disoproxil, efavirenz / lamivudine / tenofovir disoproxil
MONITOR: Coadministration of efavirenz with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Efavirenz has been associated with hepatotoxicity during postmarketing use. Among reported cases of hepatic failure, a few occurred in patients with no preexisting hepatic disease or other identifiable risk factors.
MANAGEMENT: The risk of hepatic injury should be considered when efavirenz is used in combination with other agents that are potentially hepatotoxic (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; other HIV reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Monitoring of liver function tests should occur before and during treatment, especially in patients with underlying hepatic disease (including hepatitis B or C coinfection) or marked transaminase elevations. The benefit of continued therapy with efavirenz should be considered against the unknown risks of significant liver toxicity in patients who develop persistent elevations of serum transaminases greater than five times the upper limit of normal.
References (2)
- (2001) "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals
- Elsharkawy AM, Schwab U, McCarron B, et al. (2013) "Efavirenz induced acute liver failure requiring liver transplantation in a slow drug metaboliser." J Clin Virol, 58, p. 331-3
tenofovir tezacaftor
Applies to: efavirenz / lamivudine / tenofovir disoproxil, deutivacaftor / tezacaftor / vanzacaftor
MONITOR: Coadministration with tezacaftor and/or deutivacaftor may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) efflux transporter. The mechanism is decreased clearance via inhibition of the transporter by tezacaftor and/or deutivacaftor. In study subjects, digoxin (single 0.5 mg dose) systemic exposure (AUC) increased by 1.3-fold when it was administered with tezacaftor 25 mg and ivacaftor 50 mg daily. No pharmacokinetic data are available for deutivacaftor, but increased exposures of certain P-gp substrates are expected according to prescribing information.
MANAGEMENT: Caution is advised when tezacaftor and/or deutivacaftor are used with drugs that are P-gp substrates, particularly those where minimal concentration changes may lead to serious adverse reactions.
References (6)
- (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
- (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
- (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
- (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
tenofovir deutivacaftor
Applies to: efavirenz / lamivudine / tenofovir disoproxil, deutivacaftor / tezacaftor / vanzacaftor
MONITOR: Coadministration with tezacaftor and/or deutivacaftor may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) efflux transporter. The mechanism is decreased clearance via inhibition of the transporter by tezacaftor and/or deutivacaftor. In study subjects, digoxin (single 0.5 mg dose) systemic exposure (AUC) increased by 1.3-fold when it was administered with tezacaftor 25 mg and ivacaftor 50 mg daily. No pharmacokinetic data are available for deutivacaftor, but increased exposures of certain P-gp substrates are expected according to prescribing information.
MANAGEMENT: Caution is advised when tezacaftor and/or deutivacaftor are used with drugs that are P-gp substrates, particularly those where minimal concentration changes may lead to serious adverse reactions.
References (6)
- (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
- (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
- (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
- (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
Drug and food interactions
efavirenz food
Applies to: efavirenz / lamivudine / tenofovir disoproxil
ADJUST DOSING INTERVAL: Administration with food increases the plasma concentrations of efavirenz and may increase the frequency of adverse reactions. According to the product labeling, administration of efavirenz capsules (600 mg single dose) with a high-fat/high-caloric meal (894 kcal, 54 g fat, 54% calories from fat) or a reduced-fat/normal-caloric meal (440 kcal, 2 g fat, 4% calories from fat) was associated with mean increases of 39% and 51% in efavirenz peak plasma concentration (Cmax) and 22% and 17% in systemic exposure (AUC), respectively, compared to administration under fasted conditions. For efavirenz tablets, administration of a single 600 mg dose with a high-fat/high-caloric meal (approximately 1000 kcal, 500-600 kcal from fat) resulted in a 79% increase in mean Cmax and a 28% increase in mean AUC of efavirenz relative to administration under fasted conditions.
GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of efavirenz. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.
MANAGEMENT: Efavirenz should be taken on an empty stomach, preferably at bedtime. Dosing at bedtime may improve the tolerability of nervous system symptoms such as dizziness, insomnia, impaired concentration, somnolence, abnormal dreams and hallucinations, although they often resolve on their own after the first 2 to 4 weeks of therapy . Patients should be advised of the potential for additive central nervous system effects when efavirenz is used concomitantly with alcohol or psychoactive drugs, and to avoid driving or operating hazardous machinery until they know how the medication affects them.
References (4)
- (2001) "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals
- (2023) "Product Information. Sustiva (efavirenz)." Bristol-Myers Squibb, SUPPL-59/47
- (2024) "Product Information. Stocrin (efavirenz)." Merck Sharp & Dohme (Australia) Pty Ltd
- (2024) "Product Information. Efavirenz (efavirenz)." Viatris UK Healthcare Ltd
tezacaftor food
Applies to: deutivacaftor / tezacaftor / vanzacaftor
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of tezacaftor, deutivacaftor, and vanzacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In general, the effect of grapefruit juice is concentration-, dose- and preparation- dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. The risk and/or severity of serious side effects such as liver damage may be increased.
ADJUST DOSING INTERVAL: Administration with fat-containing food may increase the oral bioavailability of vanzacaftor and deutivacaftor. Administration with a fat containing meal increased vanzacaftor systemic exposure (AUC) by 4- (low-fat meal) to 6- (high-fat meal) fold. While deutivacaftor AUC increased approximately 3- (low-fat meal) to 4- (high-fat meal) fold, relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.
MANAGEMENT: Patients treated with tezacaftor, deutivacaftor, vanzacaftor -containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit. To improve absorption, patients should be advised to take vanzacaftor and/or deutivacaftor containing medications with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products at approximately the same time of the day. A typical cystic fibrosis diet will satisfy this requirement.
References (6)
- (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
- (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
- (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
- (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
vanzacaftor food
Applies to: deutivacaftor / tezacaftor / vanzacaftor
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of tezacaftor, deutivacaftor, and vanzacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In general, the effect of grapefruit juice is concentration-, dose- and preparation- dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. The risk and/or severity of serious side effects such as liver damage may be increased.
ADJUST DOSING INTERVAL: Administration with fat-containing food may increase the oral bioavailability of vanzacaftor and deutivacaftor. Administration with a fat containing meal increased vanzacaftor systemic exposure (AUC) by 4- (low-fat meal) to 6- (high-fat meal) fold. While deutivacaftor AUC increased approximately 3- (low-fat meal) to 4- (high-fat meal) fold, relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.
MANAGEMENT: Patients treated with tezacaftor, deutivacaftor, vanzacaftor -containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit. To improve absorption, patients should be advised to take vanzacaftor and/or deutivacaftor containing medications with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products at approximately the same time of the day. A typical cystic fibrosis diet will satisfy this requirement.
References (6)
- (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
- (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
- (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
- (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
deutivacaftor food
Applies to: deutivacaftor / tezacaftor / vanzacaftor
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of tezacaftor, deutivacaftor, and vanzacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In general, the effect of grapefruit juice is concentration-, dose- and preparation- dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. The risk and/or severity of serious side effects such as liver damage may be increased.
ADJUST DOSING INTERVAL: Administration with fat-containing food may increase the oral bioavailability of vanzacaftor and deutivacaftor. Administration with a fat containing meal increased vanzacaftor systemic exposure (AUC) by 4- (low-fat meal) to 6- (high-fat meal) fold. While deutivacaftor AUC increased approximately 3- (low-fat meal) to 4- (high-fat meal) fold, relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.
MANAGEMENT: Patients treated with tezacaftor, deutivacaftor, vanzacaftor -containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit. To improve absorption, patients should be advised to take vanzacaftor and/or deutivacaftor containing medications with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products at approximately the same time of the day. A typical cystic fibrosis diet will satisfy this requirement.
References (6)
- (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
- (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
- (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
- (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
tenofovir food
Applies to: efavirenz / lamivudine / tenofovir disoproxil
Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.
References (1)
- (2001) "Product Information. Viread (tenofovir)." Gilead Sciences
Therapeutic duplication warnings
No duplication warnings were found for your selected drugs.
Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
| No interaction information available. |
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