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Drug Interactions between Norvir and pravastatin

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

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Interactions between your drugs

Moderate

pravastatin ritonavir

Applies to: pravastatin and Norvir (ritonavir)

MONITOR: Coadministration with ritonavir may decrease the plasma concentrations of pravastatin. The proposed mechanism is ritonavir induction of pravastatin metabolism via glucuronosyl transferase. In 13 healthy volunteers, the combination of ritonavir (300 mg twice a day for 3 days, then 400 mg twice a day) and saquinavir (soft gelatin capsule 400 mg twice a day) given for 14 days decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of pravastatin (40 mg once a day for 4 days) by 42% and 50%, respectively. The clinical relevance of these changes is unknown. Pravastatin appeared to have no significant effect on the plasma levels of ritonavir and saquinavir based on comparison with historical controls. It is not known to what extent, if any, the interaction may occur when ritonavir is used in lower dosages as a pharmacokinetic booster. No interaction was observed when pravastatin was given with lopinavir-ritonavir in drug interaction studies.

MANAGEMENT: Pravastatin appears to be safe when coadministered with ritonavir, although the potential for diminished hypolipidemic efficacy should be considered when antiretroviral dosages of ritonavir is prescribed. Pharmacologic response to pravastatin should be monitored more closely whenever ritonavir is added to or withdrawn from therapy, and the pravastatin dosage adjusted as necessary.

References

  1. Everett DW, Chando TJ, Didonato GC, Singhvi SM, Pan HY, Weinstein SH (1991) "Biotransformation of pravastatin sodium in humans." Drug Metab Dispos, 19, p. 740-8
  2. (2001) "Product Information. Kaletra (lopinavir-ritonavir)." Abbott Pharmaceutical
  3. Fichtenbaum CJ, Gerber JG, Rosenkranz SL, et al. (2002) "Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047." AIDS, 16, p. 569-577

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Drug and food interactions

Moderate

ritonavir food

Applies to: Norvir (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. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical

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Moderate

pravastatin food

Applies to: pravastatin

MONITOR: Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury. Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Active liver disease or unexplained transaminase elevations are contraindications to statin use.

MANAGEMENT: Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.

References

  1. (2001) "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb
  2. (2001) "Product Information. Zocor (simvastatin)." Merck & Co., Inc
  3. (2001) "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals
  4. (2001) "Product Information. Lipitor (atorvastatin)." Parke-Davis
  5. (2002) "Product Information. Altocor (lovastatin)." Andrx Pharmaceuticals
  6. (2003) "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc
  7. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  8. Cerner Multum, Inc. "Australian Product Information."
  9. (2010) "Product Information. Livalo (pitavastatin)." Kowa Pharmaceuticals America (formerly ProEthic)
View all 9 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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