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Drug Interactions between Clinagen LA 40 and Norvir

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

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Interactions between your drugs

Moderate

estradiol ritonavir

Applies to: Clinagen LA 40 (estradiol) and Norvir (ritonavir)

MONITOR: Coadministration of conjugated estrogens with ritonavir or nelfinavir may lead to decreased plasma concentrations of conjugated estrogens. The proposed mechanism may involve induction of the CYP450 3A4-mediated metabolism of conjugated estrogens by ritonavir and nelfinavir. Increased metabolism of estrogens may lead to decreased efficacy of the hormone replacement therapy. Ritonavir is a known CYP450 3A4 substrate and inhibitor; however, it has also been shown to reduce plasma concentrations of contraceptive hormones via a possible mechanism involving induction of glucuronosyltransferase and/or CYP450 hydroxylation. In addition, along with being a strong CYP450 3A4 inhibitor, nelfinavir has also been shown to possess CYP450 3A4-inducing properties.

MANAGEMENT: Dosage adjustments as well as increased clinical and laboratory monitoring should be considered whenever ritonavir or nelfinavir is added to or withdrawn from therapy with conjugated estrogens.

References

  1. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):
  2. Ouellet D, Qian J, Locke CS, Eason CJ, Cavanaugh JH "Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers." Br J Clin Pharmacol 46 (1998): 111-6
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. Dixit V, Hariparsad N, Li F, Desai P, Thummel KE, Unadkat JD "Cytochrome P450 enzymes and transporters induced by anti-human immunodeficiency virus protease inhibitors in human hepatocytes: implications for predicting clinical drug interactions." Drug Metab Dispos 35 (2007): 1853-9
  5. Cerner Multum, Inc. "Australian Product Information." O 0
  6. Faculty of Sexual & Reproductive Healthcare "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception. file:///C:/Users/df033684/Downloads/ceuguidancedruginteractionshormonal.pdf" (2016):
View all 6 references

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

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Minor

estradiol food

Applies to: Clinagen LA 40 (estradiol)

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.

References

  1. Weber A, Jager R, Borner A, et al. "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception 53 (1996): 41-7
  2. Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T "Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol." Eur J Drug Metab Pharmacokinet 20 (1995): 219-24

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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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