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Drug Interactions between Crixivan and Extendryl HC

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

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Interactions between your drugs

Major

HYDROcodone indinavir

Applies to: Extendryl HC (guaifenesin / hydrocodone) and Crixivan (indinavir)

MONITOR CLOSELY: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of hydrocodone, which is substantially metabolized by the isoenzyme. Increased hydrocodone concentrations could conceivably increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. Because hydrocodone is also partially metabolized by CYP450 2D6, the magnitude of interaction may be even greater with concomitant use of a CYP450 3A4 and a CYP450 2D6 inhibitor, or concomitant use of a drug that is a dual inhibitor of both isoenzymes.

MANAGEMENT: Extreme caution is advised if hydrocodone is prescribed with CYP450 3A4 inhibitors, particularly potent and moderate inhibitors (e.g., azole antifungal agents, protease inhibitors, aprepitant, ceritinib, ciprofloxacin, chloramphenicol, clarithromycin, cobicistat, conivaptan, crizotinib, delavirdine, diltiazem, dronedarone, erythromycin, fusidic acid, idelalisib, imatinib, letermovir, mibefradil, mifepristone, nefazodone, netupitant, quinupristin-dalfopristin, telithromycin, verapamil) or weak inhibitors that also inhibit CYP450 2D6 (e.g., abiraterone, amiodarone, cimetidine, pazopanib, ranolazine). A fatal overdose may occur following the initiation of a CYP450 3A4 inhibitor in patients already receiving hydrocodone. Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension. Following discontinuation of the CYP450 3A4 inhibitor, patients should be monitored for reduced efficacy of hydrocodone or development of withdrawal symptoms due to reduced plasma hydrocodone levels.

References

  1. Hutchinson MR, Menelaou A, Foster DJ, Coller JK, Somogyi AA "CYP2D6 and CYP3A4 involvement in the primary oxidative metabolism of hydrocodone by human liver microsomes." Br J Clin Pharmacol 57 (2004): 287-97
  2. "Product Information. Zohydro ER (hydrocodone)." Zogenix, Inc (2013):

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Drug and food interactions

Major

HYDROcodone food

Applies to: Extendryl HC (guaifenesin / hydrocodone)

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including hydrocodone. 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.

GENERALLY AVOID: Consumption of alcohol while taking some sustained-release formulations of hydrocodone may cause rapid release of the drug, resulting in high systemic levels of hydrocodone that may be potentially lethal. Alcohol apparently can disrupt the release mechanism of some sustained-release formulations. In study subjects, the rate of absorption of hydrocodone from an extended-release formulation was found to be affected by coadministration with 40% alcohol in the fasted state, as demonstrated by an average 2.4-fold (up to 3.9-fold in one subject) increase in hydrocodone peak plasma concentration and a decrease in the time to peak concentration. Alcohol also increased the extent of absorption by an average of 1.2-fold (up to 1.7-fold in one subject).

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of hydrocodone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of hydrocodone by certain compounds present in grapefruit. Increased hydrocodone concentrations could conceivably increase or prolong adverse drug effects and may cause potentially fatal respiratory depression.

MANAGEMENT: Patients taking sustained-release formulations of hydrocodone should not consume alcohol or use medications that contain alcohol. In general, potent narcotics such as hydrocodone should not be combined with alcohol. Patients should also avoid consumption of grapefruit or grapefruit juice during treatment with hydrocodone.

References

  1. "Product Information. Zohydro ER (hydrocodone)." Zogenix, Inc (2013):

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Moderate

indinavir food

Applies to: Crixivan (indinavir)

ADJUST DOSING INTERVAL: According to the manufacturer, coadministration with a meal high in calories, fat, and protein reduces the absorption of indinavir. In ten patients given indinavir in this manner, the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of indinavir decreased by an average of 84% and 77%, respectively. In contrast, grapefruit juice may have only minor effects on the oral bioavailability of indinavir. The manufacturer's package labeling states that administration of a single 400 mg dose of indinavir with 8 oz. of grapefruit juice decreased indinavir AUC by an average of 26%. Likewise, a study consisting of 14 HIV-infected subjects found no uniform nor significant changes in steady-state indinavir AUC during administration with double-strength grapefruit juice compared to water. There was, however, a delay in absorption (Tmax) due to grapefruit juice that is unlikely to be of clinical significance.

MANAGEMENT: To ensure maximal oral absorption, indinavir should be administered without food but with water 1 hour before or 2 hours after a meal. Alternatively, indinavir may be administered with other liquids such as skim milk, juice, coffee, or tea, or with a light meal (e.g., dry toast with jelly, juice, and coffee with skim milk and sugar; corn flakes, skim milk and sugar).

References

  1. "Product Information. Crixivan (indinavir)." Merck & Co., Inc PROD (2001):
  2. Yeh KC, Deutsch PJ, Haddix H, Hesney M, Hoagland V, Ju WD, Justice SJ, Osborne B, Sterrett AT, Stone JA, Woolf E, Waldman S "Single-dose pharmacokinetics of indinavir and the effect of food." Antimicrob Agents Chemother 42 (1998): 332-8
  3. Shelton MJ, Wynn HE, Newitt RG, DiFrancesco R "Effects of grapefruit juice on pharmacokinetic exposure to indinavir in HIV-positive subjects." J Clin Pharmacol 41 (2001): 435-42

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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.

See also

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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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