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Drug Interactions between acetaminophen / butalbital / caffeine and delavirdine

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

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Interactions between your drugs

Moderate

acetaminophen butalbital

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

butalbital delavirdine

Applies to: acetaminophen / butalbital / caffeine and delavirdine

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of delavirdine, which is primarily metabolized by the isoenzyme. In seven HIV-infected subjects, administration of delavirdine (400 mg three times a day for 30 days) in combination with the potent CYP450 3A4 inducer rifampin (600 mg once daily on days 16 thru 30) decreased mean delavirdine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by approximately 92%, 97% and 100%, respectively, compared to administration of delavirdine alone. Oral clearance of delavirdine also increased by nearly 27-fold in the presence of rifampin. When delavirdine (400 mg three times a day for 30 days) was given with rifabutin (300 mg once daily on days 16 thru 30) in seven HIV-positive subjects, mean delavirdine Cmax, AUC and Cmin decreased by about 75%, 84% and 95%, respectively, and oral clearance increased by approximately 5-fold. Likewise, population pharmacokinetic data from efficacy studies showed that delavirdine Cmin was reduced by approximately 90% in patients (n=8) treated with various dosages of phenytoin, phenobarbital, and/or carbamazepine who were given delavirdine 300 to 400 mg three times a day.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, caution is advised when delavirdine is used with CYP450 3A4 inducers. Pharmacologic response to the antiretroviral regimen should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the antiretroviral dosage(s) adjusted as necessary.

References (2)
  1. Borin MT, Chambers JH, Carel BJ, Gagnon S, Freimuth WW (1997) "Pharmacokinetic study of the interaction between rifampin and delavirdine mesylate." Clin Pharmacol Ther, 61, p. 544-53
  2. (2001) "Product Information. Rescriptor (delavirdine)." Pharmacia and Upjohn

Drug and food interactions

Major

acetaminophen food

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

butalbital food

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

acetaminophen food

Applies to: acetaminophen / butalbital / caffeine

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.

References (4)
  1. (2024) "Product Information. Cytisine (cytisinicline)." Consilient Health Ltd
  2. jeong sh, Newcombe D, sheridan j, Tingle M (2015) "Pharmacokinetics of cytisine, an a4 b2 nicotinic receptor partial agonist, in healthy smokers following a single dose." Drug Test Anal, 7, p. 475-82
  3. Vaughan DP, Beckett AH, Robbie DS (1976) "The influence of smoking on the intersubject variation in pentazocine elimination." Br J Clin Pharmacol, 3, p. 279-83
  4. Zevin S, Benowitz NL (1999) "Drug interactions with tobacco smoking: an update" Clin Pharmacokinet, 36, p. 425-38
Minor

caffeine food

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

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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