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Drug Interactions between cabazitaxel and Paxlovid

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

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Interactions between your drugs

Major

ritonavir cabazitaxel

Applies to: Paxlovid (nirmatrelvir / ritonavir) and cabazitaxel

GENERALLY AVOID: Coadministration with potent CYP450 3A4 inhibitors may significantly increase the plasma concentrations and toxicity of cabazitaxel, which is primarily metabolized via the isoenzyme. A drug interaction study of cabazitaxel in patients with advanced cancers (n=23), revealed that repeated administration of the potent CYP450 3A4 inhibitor ketoconazole (400 mg orally once daily), decreased the clearance and increased the systemic exposure (AUC) of cabazitaxel (5 mg/m2 intravenous) by 20% and 25%, respectively. However, one case report reviewing the coadministration of cabazitaxel (22.5 mg/m2 intravenous every 3 weeks) with lower doses of a different potent CYP450 3A4 inhibitor, clarithromycin (400 mg daily) in a 75-year-old male with castration-resistant prostate cancer did not reveal a significant change in cabazitaxel's plasma concentrations when compared to previously reported levels. This patient did experience an increase in cabazitaxel toxicity (general malaise, anorexia, dehydration), but investigators ultimately felt that this resulted from a decrease in the patient's ability to tolerate cabazitaxel.

MANAGEMENT: Given the narrow therapeutic index of cabazitaxel, concomitant use with potent CYP450 3A4 inhibitors should generally be avoided. If coadministration is clinically necessary, a 25% reduction in cabazitaxel's dose should be considered. Some authorities also recommend close monitoring for toxicity (e.g., bone marrow suppression, nausea, vomiting, severe diarrhea, peripheral neuropathy, cystitis, renal failure, pneumonitis) during coadministration. On the other hand, one publication indicated that doses of clarithromycin which result in trough concentrations around 70 ng/mL may not significantly affect cabazitaxel's plasma concentrations. Limitations such as this being a single-patient case report, lack of serial blood sampling, and unusual dosing for clarithromycin should be taken into consideration when evaluating this interaction in practice. The labeling of the inhibitor should be consulted as some inhibitors may continue to have effects on CYP450 3A4 even after the agent has been discontinued. For example, some manufacturers of itraconazole recommend avoiding concomitant use of cabazitaxel during and for 2 weeks after itraconazole treatment.

References (6)
  1. (2023) "Product Information. CABAZitaxel (Accord) (CABAZitaxel)." Accord Healthcare Pty Ltd, 2.0
  2. (2023) "Product Information. Cabazitaxel (cabazitaxel)." Dr. Reddy's Laboratories Canada Inc.
  3. (2024) "Product Information. Cabazitaxel (cabazitaxel)." Genus Pharmaceuticals Ltd
  4. (2024) "Product Information. CABAZITAXEL DR. REDDYS (cabazitaxel)." REDDY PHARMA IBERIA S.A.
  5. (2023) "Product Information. Jevtana (cabazitaxel)." sanofi-aventis
  6. Katsumi S, araki t, Yashima H, Miyazawa Y, Suzuki K, Yamamoto K (2023) "Blood concentration of cabazitaxel in a patient whose general condition worsened with concomitant use of clarithromycin." Case Rep Onc, 16, p. 503-9

Drug and food interactions

Moderate

ritonavir food

Applies to: Paxlovid (nirmatrelvir / 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)
  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical

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.


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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.