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Drug Interactions between naloxegol and voriconazole

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

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Interactions between your drugs

Major

voriconazole naloxegol

Applies to: voriconazole and naloxegol

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of naloxegol, which is primarily metabolized by the isoenzyme. When a single 25 mg dose of naloxegol was administered during multiple dosing of 400 mg once daily ketoconazole, a potent CYP450 3A4 inhibitor, naloxegol peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 9.6- and 12.9-fold, respectively. Increased exposure to naloxegol may precipitate opioid withdrawal symptoms such as hyperhidrosis, lacrimation, rhinorrhea, chills, diarrhea, abdominal pain, anxiety, insomnia, irritability, restlessness, and yawning.

MANAGEMENT: Concomitant use of naloxegol with potent CYP450 3A4 inhibitors such as clarithromycin, telithromycin, itraconazole, ketoconazole, posaconazole, voriconazole, conivaptan, idelalisib, nefazodone, cobicistat, delavirdine, and protease inhibitors is considered contraindicated. Some authorities consider concomitant administration of naloxegol and itraconazole to be contraindicated during and for 2 weeks after treatment with itraconazole.

References (4)
  1. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Cerner Multum, Inc. "Australian Product Information."
  4. (2014) "Product Information. Movantik (naloxegol)." Astra-Zeneca Pharmaceuticals

Drug and food interactions

Major

naloxegol food

Applies to: naloxegol

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of naloxegol. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In pharmacokinetic studies, naloxegol systemic exposure (AUC) was increased approximately 3.5-fold by the moderate CYP450 3A4 inhibitor diltiazem and nearly 13-fold by the potent inhibitor ketoconazole. The interaction has not been studied with grapefruit juice. 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. Increased exposure to naloxegol may precipitate opioid withdrawal symptoms such as hyperhidrosis, lacrimation, rhinorrhea, chills, diarrhea, abdominal pain, anxiety, insomnia, irritability, restlessness, and yawning.

ADJUST DOSING INTERVAL: Food may increase the rate and extent of naloxegol absorption. When administered with a high-fat meal, naloxegol peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 30% and 45%, respectively. In clinical trials, naloxegol was given on an empty stomach approximately 1 hour prior to the first meal in the morning.

MANAGEMENT: Patients treated with naloxegol should avoid consumption of grapefruit and grapefruit juice. Naloxegol should be taken on an empty stomach at least 1 hour prior to the first meal of the day or 2 hours after the meal.

References (1)
  1. (2014) "Product Information. Movantik (naloxegol)." Astra-Zeneca Pharmaceuticals
Moderate

voriconazole food

Applies to: voriconazole

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.

References (2)
  1. (2002) "Product Information. VFEND (voriconazole)." Pfizer U.S. Pharmaceuticals
  2. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67

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.

Further information

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