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Drug Interactions between Atripla and itraconazole

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

itraconazole efavirenz

Applies to: itraconazole and Atripla (efavirenz / emtricitabine / tenofovir)

GENERALLY AVOID: Coadministration with efavirenz can reduce the plasma concentrations and therapeutic efficacy of itraconazole. The mechanism is efavirenz induction of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of itraconazole. When efavirenz (600 mg orally daily for 14 days) was administered with itraconazole (200 mg orally every 12 hours for 28 days) in 18 study subjects, the systemic exposure (AUC) of itraconazole decreased by 39%, and the maximum and minimum plasma concentrations decreased by 37% and 44%, respectively. Plasma concentrations of hydroxyitraconazole were similarly reduced. In contrast, itraconazole had no significant effect on the pharmacokinetics of efavirenz.

MANAGEMENT: Coadministration of itraconazole with efavirenz should generally be avoided. Some authorities recommend avoiding concomitant use from 2 weeks before and during treatment with itraconazole. No dosage recommendations for itraconazole are available when used in combination with efavirenz. The manufacturer of efavirenz recommends use of other antifungal agents.

References

  1. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  2. (2001) "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals
  3. Cerner Multum, Inc. "Australian Product Information."

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Moderate

efavirenz tenofovir

Applies to: Atripla (efavirenz / emtricitabine / tenofovir) and Atripla (efavirenz / emtricitabine / tenofovir)

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

  1. (2001) "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals
  2. 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

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Moderate

efavirenz emtricitabine

Applies to: Atripla (efavirenz / emtricitabine / tenofovir) and Atripla (efavirenz / emtricitabine / tenofovir)

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

  1. (2001) "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals
  2. 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

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Drug and food interactions

Moderate

itraconazole food

Applies to: itraconazole

ADJUST DOSING INTERVAL: Food increases the absorption of itraconazole capsules but decreases the absorption of itraconazole oral solution. Cola beverages may increase the bioavailability of itraconazole capsules. Itraconazole capsules require an acidic gastric pH for adequate dissolution and subsequent absorption. Cola beverages help lower gastric pH and improve absorption.

GENERALLY AVOID: Grapefruit juice may impair the absorption of itraconazole capsules, resulting in decreased antifungal effects. In a small, randomized, crossover study, the administration of itraconazole capsules with double-strength grapefruit juice (compared to water) was associated with significantly decreased (43%) plasma concentrations of itraconazole and its pharmacologically active hydroxy metabolite, as well as delayed times to reach peak concentrations of both. The exact mechanism of interaction is unknown but may involve reduced absorption of itraconazole secondary to enhanced activity of intestinal P-glycoprotein drug efflux pumps and delayed gastric emptying induced by certain compounds present in grapefruits. Another study reported no pharmacokinetic changes with single-strength grapefruit juice. Whether or not these observations apply to itraconazole oral solution is unknown.

MANAGEMENT: The manufacturer recommends that the capsules be taken immediately after a full meal and the solution be taken on an empty stomach to ensure maximal absorption. Cola beverages may help increase the bioavailability of itraconazole capsules, particularly in patients with hypochlorhydria or those treated concomitantly with gastric acid suppressants. Until more information is available, it may be advisable to avoid the consumption of grapefruits and grapefruit juice during itraconazole therapy.

References

  1. Van Peer A, Woestenborghs R, Heykants J, et al. (1989) "The effects of food and dose on the oral systemic availability of itraconazole in healthy subjects." Eur J Clin Pharmacol, 36, p. 423-6
  2. Wishart JM (1987) "The influence of food on the pharmacokinetics of itraconazole in patients with superficial fungal infection." J Am Acad Dermatol, 17, p. 220-3
  3. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  4. Barone JA, Koh JG, Bierman RH, Colaizzi JL, Swanson KA, Gaffar MC, Moskovitz BL, Mechlinski W, Van de Velde V (1993) "Food interaction and steady-state pharmacokinetics of itraconazole capsules in healthy male volunteers." Antimicrob Agents Chemother, 37, p. 778-84
  5. Zimmermann T, Yeates RA, Albrecht M, Laufen H, Wildfeuer A (1994) "Influence of concomitant food intake on the gastrointestinal absorption of fluconazole and itraconazole in japanese subjects." Int J Clin Pharmacol Res, 14, p. 87-93
  6. (2022) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  7. Kawakami M, Suzuki K, Ishizuka T, Hidaka T, Matsuki Y, Nakamura H (1998) "Effect of grapefruit juice on pharmacokinetics of itraconazole in healthy subjects." Int J Clin Pharmacol Ther, 36, p. 306-8
  8. Barone JA, Moskotitz BL, Guarnieri J, Hassell AE, Colaizzi JL, Bierman RH, Jessen L (1998) "Food interaction and steady-state pharmacokinetics of itraconazole oral solution in healthy volunteers." Pharmacotherapy, 18, p. 295-301
  9. Penzak SR, Gubbins PO, Gurley BJ, Wang PL, Saccente M (1999) "Grapefruit juice decreases the systemic availability of itraconazole capsules in healthy volunteers." Ther Drug Monit, 21, p. 304-9
  10. Katz HI (1999) "Drug interactions of the newer oral antifungal agents." Br J Dermatol, 141, p. 26-32
View all 10 references

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Moderate

efavirenz food

Applies to: Atripla (efavirenz / emtricitabine / tenofovir)

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.

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

  1. (2001) "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals

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Minor

tenofovir food

Applies to: Atripla (efavirenz / emtricitabine / tenofovir)

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

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Therapeutic duplication warnings

No 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.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor 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.
Unknown No interaction information available.

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