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Drug Interactions between ritonavir and ziprasidone

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

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Interactions between your drugs

Minor

ritonavir ziprasidone

Applies to: ritonavir 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

  1. "Product Information. Geodon (ziprasidone)." Pfizer U.S. Pharmaceuticals PROD (2001):
  2. Miceli JJ, Smith M, Robarge L, Morse T, Laurent A "The effects of ketoconazole on ziprasidone pharmacokinetics--a placebo-controlled crossover study in healthy volunteers." Br J Clin Pharmacol 49(suppl 1) (2000): s71-6
  3. Prakash C, Kamel A, Cui D, Whalen RD, Miceli JJ, Tweedie D "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) (2000): 35S-42S
  4. Wilner KD, Hansen RA, Folger CJ, Geoffroy P "The pharmacokinetics of ziprasidone in healthy volunteers treated with cimetidine or antacid." Br J Clin Pharmacol 49(Suppl 1) (2000): 57S-60S
View all 4 references

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Drug and food interactions

Moderate

ritonavir food

Applies to: ritonavir

ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.

References

  1. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):

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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

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