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Drug Interactions between Carbatrol and Trycet

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: Carbatrol (carbamazepine) and Trycet (acetaminophen / 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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Moderate

acetaminophen carBAMazepine

Applies to: Trycet (acetaminophen / propoxyphene) and Carbatrol (carbamazepine)

MONITOR: Limited data suggest that carbamazepine may increase the potential hepatotoxicity of acetaminophen and decrease its pharmacologic effects. The mechanism may be related to accelerated CYP450 metabolism of acetaminophen with consequent increase of hepatotoxic metabolites. This interaction is of greatest concern in cases of acetaminophen overdose.

MANAGEMENT: Until more information is available, the use of this combination over a prolonged period of time should probably be avoided. Monitoring for clinical and laboratory evidence of hepatotoxicity is recommended.

References

  1. Miners JO, Attwood J, Birkett DJ "Determinants of acetaminophen metabolism: effect of inducers and inhibitors of drug metabolism on acetaminophen's metabolic pathways." Clin Pharmacol Ther 35 (1984): 480-6
  2. Perucca E, Richens A "Paracetamol disposition in normal subjects and in patients treated with antiepileptic drugs." Br J Clin Pharmacol 7 (1979): 201-6
  3. Smith JA, Hine ID, Beck P, Routledge PA "Paracetamol toxicity: is enzyme induction important?" Hum Toxicol 5 (1986): 383-5

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Drug and food interactions

Major

propoxyphene food

Applies to: Trycet (acetaminophen / 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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Major

acetaminophen food

Applies to: Trycet (acetaminophen / propoxyphene)

GENERALLY AVOID: Chronic, excessive consumption of alcohol may increase the risk of acetaminophen-induced hepatotoxicity, which has included rare cases of fatal hepatitis and frank hepatic failure requiring liver transplantation. The proposed mechanism is induction of hepatic microsomal enzymes during chronic alcohol use, which may result in accelerated metabolism of acetaminophen and increased production of potentially hepatotoxic metabolites.

MANAGEMENT: In general, chronic alcoholics should avoid regular or excessive use of acetaminophen. Alternative analgesic/antipyretic therapy may be appropriate in patients who consume three or more alcoholic drinks per day. However, if acetaminophen is used, these patients should be cautioned not to exceed the recommended dosage (maximum 4 g/day in adults and children 12 years of age or older).

References

  1. Kaysen GA, Pond SM, Roper MH, Menke DJ, Marrama MA "Combined hepatic and renal injury in alcoholics during therapeutic use of acetaminophen." Arch Intern Med 145 (1985): 2019-23
  2. O'Dell JR, Zetterman RK, Burnett DA "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA 255 (1986): 2636-7
  3. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med 104 (1986): 399-404
  4. Thummel KE, Slattery JT, Nelson SD "Mechanism by which ethanol diminishes the hepatotoxicity of acetaminophen." J Pharmacol Exp Ther 245 (1988): 129-36
  5. McClain CJ, Kromhout JP, Peterson FJ, Holtzman JL "Potentiation of acetaminophen hepatotoxicity by alcohol." JAMA 244 (1980): 251-3
  6. Kartsonis A, Reddy KR, Schiff ER "Alcohol, acetaminophen, and hepatic necrosis." Ann Intern Med 105 (1986): 138-9
  7. Prescott LF, Critchley JA "Drug interactions affecting analgesic toxicity." Am J Med 75 (1983): 113-6
  8. "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical PROD (2002):
  9. Whitcomb DC, Block GD "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA 272 (1994): 1845-50
  10. Bonkovsky HL "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  11. Nelson EB, Temple AR "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  12. Zimmerman HJ, Maddrey WC "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology 22 (1995): 767-73
View all 12 references

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Moderate

carBAMazepine food

Applies to: Carbatrol (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

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