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Drug Interactions between Carnexiv and Norvir

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

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Interactions between your drugs

Moderate

carBAMazepine ritonavir

Applies to: Carnexiv (carbamazepine) and Norvir (ritonavir)

MONITOR: Coadministration with ritonavir may significantly increase the plasma concentrations and pharmacologic effects of carbamazepine. The proposed mechanism is ritonavir inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of carbamazepine. There have been case reports of patients stabilized on carbamazepine therapy who developed ataxia, disorientation, vertigo, vomiting, and transient liver dysfunction following the addition of ritonavir, subsequently requiring discontinuation of ritonavir or substantial reductions of carbamazepine dosage. The effect of carbamazepine on ritonavir clearance has not been reported. Theoretically, ritonavir plasma levels may decrease due to carbamazepine induction of CYP450 3A4, which also metabolizes ritonavir.

MANAGEMENT: Given its narrow therapeutic index, caution is advised if carbamazepine must be used concomitantly with ritonavir. Carbamazepine levels and pharmacologic effects should be closely monitored and the dosage adjusted accordingly, particularly following initiation or discontinuation of ritonavir in patients who are stabilized on their anticonvulsant regimen. Patients should be advised to contact their physician if they develop signs of carbamazepine toxicity such as ataxia, dizziness, nausea, vomiting, and visual disturbances. In addition, it may be appropriate to monitor patients for potentially reduced antiretroviral response due to decreased plasma levels of ritonavir and other antiretroviral agents induced by carbamazepine.

References

  1. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):
  2. Spina E, Pisani F, Perucca E "Clinically significant pharmacokinetic drug interactions with carbamazepine - an update." Clin Pharmacokinet 31 (1996): 198-214
  3. Michalets EL "Update: clinically significant cytochrome P-450 drug interactions." Pharmacotherapy 18 (1998): 84-112
  4. Brooks J, Daily J, Schwamm L "Protease inhibitors and anticonvulsants." AIDS Clin Care 9 (1997): 87,90
  5. Barry M, Gibbons S, Back D, Mulcahy F "Protease inhibitors in patients with HIV disease. Clinically important pharmacokinetic considerations." Clin Pharmacokinet 32 (1997): 194-209
  6. Sommadossi JP "HIV protease inhibitors: pharmacologic and metabolic distinctions." AIDS 13 (1999): s29-40
  7. Dresser GK, Spence JD, Bailey DG "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet 38 (2000): 41-57
  8. Kato Y, Fujii T, Mizoguchi N, et al. "Potential interaction between ritonavir and carbamazepine." Pharmacotherapy 20 (2000): 851-4
  9. Durant J, Clevenbergh P, Garraffo R, Halfon P, Icard S, DelGiudice P, Montagne N, Schapiro JM, Dellamonica P "Importance of protease inhibitor plasma levels in HIV-infected patients treated with genotypic-guided therapy: pharmacological data from the Viradapt Study." Aids 14 (2000): 1333-9
  10. Burman W, Orr L "Carbamazepine toxicity after starting combination antiretroviral therapy including ritonavir and efavirenz." Aids 14 (2000): 2793-4
  11. Mateu-de Antonio J, Grau S, Gimeno-Bayon JL, Carmona A "Ritonavir-induced carbamazepine toxicity." Ann Pharmacother 35 (2001): 125-6
  12. Garcia AB, Ibarra AL, Etessam JP, et al. "Protease inhibitor-induced carbamazepine toxicity." Clin Neuropharmacol 23 (2000): 216-8
  13. Liedtke MD, Lockhart SM, Rathbun RC "Anticonvulsant and antiretroviral interactions." Ann Pharmacother 38 (2004): 482-9
  14. Bates DE, Herman RJ "Carbamazepine toxicity induced by lopinavir/ritonavir and nelfinavir." Ann Pharmacother 40 (2006): 1190-5
View all 14 references

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Drug and food interactions

Moderate

carBAMazepine food

Applies to: Carnexiv (carbamazepine)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.

References

  1. "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals PROD (2002):
  2. Garg SK, Kumar N, Bhargava VK, Prabhakar SK "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther 64 (1998): 286-8
  3. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77

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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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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

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