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Drug Interactions between Capacet and Carnexiv

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

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Interactions between your drugs

Moderate

acetaminophen carBAMazepine

Applies to: Capacet (acetaminophen / butalbital / caffeine) and Carnexiv (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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Moderate

acetaminophen butalbital

Applies to: Capacet (acetaminophen / butalbital / caffeine) and Capacet (acetaminophen / butalbital / caffeine)

MONITOR: Barbiturates may increase the hepatotoxic potential of acetaminophen and decrease its therapeutic effects. The mechanism may be related to accelerated CYP450 metabolism of acetaminophen with consequent increase in hepatotoxic metabolites. This interaction is of greatest concern in cases of acetaminophen overdose.

MANAGEMENT: Monitoring for altered efficacy and safety is recommended. Prolonged use or high doses of acetaminophen should be avoided by patients on barbiturate therapy.

References

  1. Pirotte JH "Apparent potentiation by phenobarbital of hepatotoxicity from small doses of acetaminophen." Ann Intern Med 101 (1984): 403
  2. Douidar SM, Ahmed AE "A novel mechanism for the enhancement of acetaminophen hepatotoxicity by phenobarbital." J Pharmacol Exp Ther 240 (1987): 578-83
  3. Wright N, Prescott LF "Potentiation by previous drug therapy of hepatotoxicity following paracetamol overdose." Scott Med J 18 (1973): 56-8
  4. Bock KW, Wiltfang J, Blume R, Ullrich D, Bircher J "Paracetamol as a test drug to determine glucuronide formation in man: effects of inducers and of smoking." Eur J Clin Pharmacol 31 (1987): 677-83
View all 4 references

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Minor

carBAMazepine butalbital

Applies to: Carnexiv (carbamazepine) and Capacet (acetaminophen / butalbital / caffeine)

Coadministration with a barbiturate may decrease the plasma concentrations of carbamazepine and increase concentrations of its active 10,11-epoxide metabolite. The mechanism is barbiturate induction of CYP450 3A4, the isoenzyme responsible for the metabolism of carbamazepine to carbamazepine-10,11-epoxide (CBZ-E). In clinical and pharmacokinetic studies, carbamazepine levels were typically lower when the drug was administered with phenobarbital than when administered alone, and CBZ-E levels generally higher. However, one study reported an increased clearance and reduced half-life of single-dose CBZ-E in six epileptic patients who were receiving phenobarbital compared to six drug-free healthy volunteers, which would seem to suggest an induction of CBZ-E metabolism also. The clinical significance of these changes are unknown, particularly since the anticonvulsant activity of CBZ-E relative to the parent compound has not been established. Until more data are available, it may be reasonable to monitor serum carbamazepine levels more closely whenever a barbiturate (if used for more than a few days) is added to or withdrawn from therapy.

References

  1. Dam M, Jensen A, Christiansen J "Plasma level and effect of carbamazepine in grand mal and psychomotor epilepsy." Acta Neurol Scand S75 (1975): 33-8
  2. Eichelbaum M, Kothe KW, Hoffmann F, von Unruh GE "Kinetics and metabolism of carbamazepine during combined antiepileptic drug therapy." Clin Pharmacol Ther 26 (1979): 366-71
  3. Ramsay RE, McManus DQ, Guterman A, et al. "Carbamazepine metabolism in humans: effect of concurrent anticonvulsant therapy." Ther Drug Monit 12 (1990): 235-41
  4. Cereghino JJ, Brock JT, Van Meter JC, et al. "The efficacy of carbamazepine combinations in epilepsy." Clin Pharmacol Ther 18 (1975): 733-41
  5. Spina E, Martines C, Fazio A, Trio R, Pisani F, Tomson T "Effect of phenobarbital on the pharmacokinetics of carbamazepine-10, 11-epoxide, an active metabolite of carbamazepine." Ther Drug Monit 13 (1991): 109-12
  6. "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals PROD (2002):
  7. Tomson T, Spina E, Wedlund JE "Minor additive inducing effects of phenobarbital on carbamazepine clearance in patients on combined carbamazepine-phenytoin therapy." Ther Drug Monit 9 (1987): 117-9
  8. Benetello P, Furlanut M "Primidone-carbamazepine interaction: clinical consequences." Int J Clin Pharmacol Res 7 (1987): 165-8
  9. Liu H, Delgado MR "Interactions of phenobarbital and phenytoin with carbamazepine and its metabolites' concentrations, concentration ratios, and level dose ratios in epileptic children." Epilepsia 36 (1995): 249-54
View all 9 references

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Drug and food interactions

Major

acetaminophen food

Applies to: Capacet (acetaminophen / butalbital / caffeine)

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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Major

butalbital food

Applies to: Capacet (acetaminophen / butalbital / caffeine)

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

References

  1. Gupta RC, Kofoed J "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J 94 (1966): 863-5
  2. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med 51 (1971): 346-51
  3. Saario I, Linnoila M "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh) 38 (1976): 382-92
  4. Stead AH, Moffat AC "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol 2 (1983): 5-14
  5. Seixas FA "Drug/alcohol interactions: avert potential dangers." Geriatrics 34 (1979): 89-102
View all 5 references

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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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Minor

caffeine food

Applies to: Capacet (acetaminophen / butalbital / caffeine)

The effect of grapefruit juice on the pharmacologic activity of caffeine is controversial. One report suggests that grapefruit juice increases the effect of caffeine. The proposed mechanism is inhibition of cytochrome P-450 metabolism of caffeine. However, a well-conducted pharmacokinetic/pharmacodynamic study did not demonstrate this effect. The clinical significance of this potential interaction is unknown.

References

  1. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
  2. Maish WA, Hampton EM, Whitsett TL, Shepard JD, Lovallo WR "Influence of grapefruit juice on caffeine pharmacokinetics and pharmacodynamics." Pharmacotherapy 16 (1996): 1046-52

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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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