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Drug Interactions between Crixivan and ziprasidone

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

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Interactions between your drugs

Minor

indinavir ziprasidone

Applies to: Crixivan (indinavir) and ziprasidone

Coadministration with inhibitors of CYP450 3A4 may only modestly increase the plasma concentrations of ziprasidone, as less than 1/3 of ziprasidone metabolic clearance occurs via oxidation mediated by CYP450 3A4. In 14 healthy subjects, coadministration with the potent CYP450 3A4 inhibitor ketoconazole (400 mg orally once a day for 5 days) increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of ziprasidone (40 mg single oral dose) by approximately 1/3 compared to placebo. These changes, although statistically significant, were not considered clinically important. There were also no serious adverse events, laboratory or ECG abnormalities, or clinically significant alterations in vital signs throughout the study. Likewise, in 10 healthy subjects, the nonspecific CYP450 inhibitor cimetidine (800 mg orally once a day for 3 days) increased the AUC of ziprasidone (40 mg single oral dose) by just 6% compared to when ziprasidone was administered alone. These findings suggest that ziprasidone dose modifications are unlikely to be necessary in patients receiving potent CYP450 3A4 inhibitors.

References (4)
  1. (2001) "Product Information. Geodon (ziprasidone)." Pfizer U.S. Pharmaceuticals
  2. Miceli JJ, Smith M, Robarge L, Morse T, Laurent A (2000) "The effects of ketoconazole on ziprasidone pharmacokinetics--a placebo-controlled crossover study in healthy volunteers." Br J Clin Pharmacol, 49(suppl 1), s71-6
  3. Prakash C, Kamel A, Cui D, Whalen RD, Miceli JJ, Tweedie D (2000) "Identification of the major human liver cytochrome P450 isoform(s) responsible for the formation of the primary metabolites of ziprasidone and prediction of possible drug interactions." Br J Clin Pharmacol, 49(Suppl 1), 35S-42S
  4. Wilner KD, Hansen RA, Folger CJ, Geoffroy P (2000) "The pharmacokinetics of ziprasidone in healthy volunteers treated with cimetidine or antacid." Br J Clin Pharmacol, 49(Suppl 1), 57S-60S

Drug and food interactions

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 (3)
  1. (2001) "Product Information. Crixivan (indinavir)." Merck & Co., Inc
  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 (1998) "Single-dose pharmacokinetics of indinavir and the effect of food." Antimicrob Agents Chemother, 42, p. 332-8
  3. Shelton MJ, Wynn HE, Newitt RG, DiFrancesco R (2001) "Effects of grapefruit juice on pharmacokinetic exposure to indinavir in HIV-positive subjects." J Clin Pharmacol, 41, p. 435-42
Moderate

ziprasidone food

Applies to: ziprasidone

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc

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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