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Drug Interactions between Agenerase and Geodon

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

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Interactions between your drugs

Minor

amprenavir ziprasidone

Applies to: Agenerase (amprenavir) and Geodon (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

  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
View all 4 references

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Drug and food interactions

Moderate

amprenavir food

Applies to: Agenerase (amprenavir)

GENERALLY AVOID: Administration with a high-fat meal may decrease the oral bioavailability of amprenavir. The mechanism is unknown. In healthy volunteers, consumption of a standardized high-fat meal decreased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amprenavir (1200 mg single oral dose) by 36% and 21%, respectively, compared to administration in the fasted state. The time to reach Cmax (Tmax) was increased 44% following a high-fat meal.

Grapefruit juice does not appear to significantly affect the pharmacokinetics of amprenavir. In 12 healthy volunteers, administration with grapefruit juice (200 mL) decreased the mean peak plasma concentration (Cmax) of amprenavir (1200 mg single oral dose) by 22% compared to water. The median time to reach Cmax (Tmax) was prolonged from 0.75 to 1.13 hours. These pharmacokinetic changes are not thought to be clinically significant, since antiretroviral response is more closely associated with systemic exposure (AUC) and trough plasma concentration (Cmin), which were not affected in the study.

MANAGEMENT: Amprenavir may be taken with or without food, but should not be taken with a high-fat meal.

References

  1. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  2. Demarles D, Gillotin C, Bonaventure-Paci S, Vincent I, Fosse S, Taburet AM (2002) "Single-dose pharmacokinetics of amprenavir coadministered with grapefruit juice." Antimicrob Agents Chemother, 46, p. 1589-1590

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Moderate

ziprasidone food

Applies to: Geodon (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

  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
View all 4 references

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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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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