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Drug Interactions between Carnexiv and propoxyphene

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

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Interactions between your drugs

Major

carBAMazepine propoxyphene

Applies to: Carnexiv (carbamazepine) and propoxyphene

GENERALLY AVOID: Coadministration with propoxyphene may significantly increase the plasma concentrations of carbamazepine. The proposed mechanism is propoxyphene inhibition of carbamazepine metabolism via hepatic CYP450 microsomal enzymes. In a study of six patients maintained on carbamazepine monotherapy, serum carbamazepine levels increased by an average of 66% after the initiation of propoxyphene 65 mg three times daily for six days. A further increase was seen in three of the patients after an additional week of propoxyphene. One patient developed clinical signs of carbamazepine toxicity and had to discontinue taking propoxyphene. There have also been case reports of toxicity attributed to the interaction, with increases in serum carbamazepine level by up to nearly 8-fold following initiation of propoxyphene. A few cases have resulted in hospitalization, coma, and even death. Elderly patients may be particularly susceptible. In a group of Swedish elderly patients who were part of a drug-dispensing program, the dosages of carbamazepine and propoxyphene were lower among patients who used the combination compared to those who used only one of the drugs. However, despite the carbamazepine dosage being approximately one-third lower in the combination group, the mean serum carbamazepine level was 25% higher and the incidence of adverse effects was also significantly higher.

MANAGEMENT: Given the availability of alternative analgesics, the use of propoxyphene in combination with carbamazepine should generally be avoided. A dose adjustment of carbamazepine may be required if concomitant use is necessary, and serum carbamazepine levels should be closely monitored. Patients should be advised to seek medical attention if they develop potential signs and symptoms of carbamazepine toxicity such as headache, nausea, dizziness, slurred speech, nystagmus, visual disturbances, tremors, and ataxia.

References

  1. Oles KS, Mirza W, Penry JK "Catastrophic neurologic signs due to drug interaction: Tegretol and Darvon." Surg Neurol 32 (1989): 144-51
  2. Dam M, Christiansen J "Interaction of propoxyphene with carbamazepine." Lancet 2 (1977): 509
  3. Hansen BS, Dam M, Brandt J, et al. "Influence of dextropropoxyphene on steady state serum levels and protein binding of three anti-epileptic drugs in man." Acta Neurol Scand 61 (1980): 357-67
  4. Kubacka RT, Ferrante JA "Carbamazepine-propoxyphene interaction." Clin Pharm 2 (1983): 104
  5. Yu YL, Huang CY, Chin D, et al. "Interaction between carbamazepine and dextropropoxyphene." Postgrad Med J 62 (1986): 231-3
  6. Dam M, Kristensen CB, Hansen BS, Christiansen J "Interaction between carbamazepine and propoxyphene in man." Acta Neurol Scand 56 (1977): 603-7
  7. Baciewicz AM "Carbamazepine drug interactions." Ther Drug Monit 8 (1986): 305-17
  8. Allen S "Cerebellar dysfunction following dextropropoxyphene-induced carbamazepine toxicity." Postgrad Med J 70 (1994): 764
  9. Bergendal L, Friberg A, Schaffrath A "Potential drug-drug interactions in 5,125 mostly elderly out-patients in gothenburg, sweden." Pharm World Sci 17 (1995): 152-7
  10. Spina E, Pisani F, Perucca E "Clinically significant pharmacokinetic drug interactions with carbamazepine - an update." Clin Pharmacokinet 31 (1996): 198-214
  11. "True allergy or other symptom?" ISMP Medication Safety Alert! 14 (2009): 3
View all 11 references

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Drug and food interactions

Major

propoxyphene food

Applies to: propoxyphene

GENERALLY AVOID: Alcohol may have additive CNS- and/or respiratory-depressant effects with propoxyphene. Misuse of propoxyphene, either alone or in combination with other CNS depressants, has been a major cause of drug-related deaths, particularly in patients with a history of emotional disturbances, suicidal ideation, or alcohol and drug abuse.

MANAGEMENT: The use of alcohol during propoxyphene therapy should be avoided. Patients should be warned not to exceed the recommended dosage of propoxyphene and to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company PROD (2001):

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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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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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