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Drug Interactions between conjugated estrogens and Fioricet

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

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Moderate

acetaminophen butalbital

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

conjugated estrogens butalbital

Applies to: conjugated estrogens and Fioricet (acetaminophen / butalbital / caffeine)

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of estrogens and progestins. Estrogens have been shown in in vitro and in vivo studies to be partially metabolized by CYP450 3A4, and other steroids including progestins are also believed to undergo metabolism by this isoenzyme. The interaction has been reported primarily with oral contraceptives. There have been case reports of menstrual breakthrough bleeding or unwanted pregnancy in women receiving low-dose oral contraceptives following the addition of known CYP450 3A4 inducers such as carbamazepine, phenobarbital, phenytoin, rifampin, and St. John's wort. Inadequate response to estrogen replacement therapy has also been reported in a patient treated with phenytoin. Aminoglutethimide, a CYP450 3A4 inducer, has been shown to decrease medroxyprogesterone and megestrol serum levels by 74% in six patients stabilized on their progestin regimen.

MANAGEMENT: Pharmacologic response to estrogens and progestins should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the hormone dosage adjusted as necessary. For patients receiving hormonal contraceptives, additional or alternative non-hormonal birth control may be advisable during concomitant therapy with CYP450 3A4 inducers. Additional or alternative non-hormonal birth control may be recommended beyond discontinuation of the CYP450 3A4 inducer(s). Individual product labeling should be consulted for specific time frames. Intrauterine systems are unlikely to be significantly affected because of their local action. Input from a gynecologist or similar expert on adequate contraception, including emergency contraception, should be sought as needed. Patients using replacement therapy should be advised to notify their physician if they experience inadequate control of symptoms associated with estrogen deficiency (e.g., nocturnal sweating, vasomotor disturbances, atrophic vaginitis) or changes in the uterine bleeding profile.

References (47)
  1. Crawford P, Chadwick DJ, Martin C, et al. (1990) "The interaction of phenytoin and carbamazepine with combined oral contraceptive steroids." Br J Clin Pharmacol, 30, p. 892-6
  2. Venkatesan K (1992) "Pharmacokinetic drug interactions with rifampicin." Clin Pharmacokinet, 22, p. 47-65
  3. Borcherding SM, Baciewicz AM, Self TH (1992) "Update on rifampin drug interactions." Arch Intern Med, 152, p. 711-6
  4. Weber JC (1984) "Interaction between oral contraceptives and griseofulvin." Br Med J, 288, p. 1125-6
  5. McDaniel PA, Caldroney RD (1986) "Oral contraceptives and griseofulvin interaction." Drug Intell Clin Pharm, 20, p. 384
  6. Cote J (1990) "Interaction of griseofulvin and oral contraceptives." J Am Acad Dermatol, 22, p. 124-5
  7. Baciewicz AM (1985) "Oral contraceptive drug interactions." Ther Drug Monit, 7, p. 26-35
  8. Skolnick JL, Stoler BS, Katz DB, Anderson WH (1976) "Rifampin, oral contraceptives, and pregnancy." JAMA, 236, p. 1382
  9. Lundgren S, Lonning PE, Aakvaag A, Kvinnsland S, Lnning PE (1990) "Influence of aminoglutethimide on the metabolism of medroxyprogesterone acetate and megestrol acetate in postmenopausal patients with advanced breast cancer." Cancer Chemother Pharmacol, 27, p. 101-5
  10. Halpenny O, Bye A, Cranny A, Feely J, Daly PA (1990) "Influence of aminoglutethimide on plasma levels of medroxyprogesterone acetate." Med Oncol Tumor Pharmacother, 7, p. 241-7
  11. Mumford JP (1974) "Letter: Drugs affecting oral contraceptives." Br Med J, 2, p. 333-4
  12. Back DJ, Bates M, Bowden A, et al. (1980) "The interaction of phenobarbital and other anticonvulsants with oral contraceptive steroid therapy." Contraception, 22, p. 495-503
  13. Dossetor J (1975) "Drug interactions with oral contraceptives." Br Med J, 4, p. 467-8
  14. Baciewicz AM, Self TH (1984) "Rifampin drug interactions." Arch Intern Med, 144, p. 1667-71
  15. Nocke-finck L (1973) "Effects of rifampicin on menstral cycle and on estrogen excretion in patients taking oral contraceptives." JAMA, 226, p. 378
  16. Bolt HM, Bolt M, Kappus H (1977) "Interaction of rifampicin treatment with pharmacokinetics and metabolism of ethinyloestradiol in man." Acta Endocrinol (Copenh), 85, p. 189-97
  17. Back DJ, Breckenridge AM, Crawford FE, et al. (1980) "The effect of rifampicin on the pharmacokinetics of ethynylestradiol in women." Contraception, 21, p. 135-43
  18. Furlan AJ, Rothner AD (1974) "Anti-epileptic drugs and failure of oral contraceptives." Lancet, 1, p. 1113
  19. Coulam CB, Annegers JF (1979) "Do anticonvulsants reduce the efficacy of oral contraceptives?" Epilepsia, 20, p. 519-26
  20. Szoka PR, Edgren RA (1988) "Drug interactions with oral contraceptives: compilation and analysis of an adverse experience report database." Fertil Steril, 49, s31-8
  21. Mattson RH, Cramer JA, Darney PD, Naftolin F (1986) "Use of oral contraceptives by women with epilepsy." JAMA, 256, p. 238-40
  22. van Dijke CP, Weber JC (1984) "Interaction between oral contraceptives and griseofulvin." Br Med J (Clin Res Ed), 288, p. 1125-6
  23. Laengner H, Detering K (1974) "Letter: Anti-epileptic drugs and failure of oral contraceptives." Lancet, 2, p. 600
  24. Janz D, Schmidt D (1974) "Letter: Anti-epileptic drugs and failure of oral contraceptives." Lancet, 1, p. 1113
  25. Curran MA (1986) "Drug interactions with the pill." Med J Aust, 144, p. 670-1
  26. Back DJ, Orme ML (1990) "Pharmacokinetic drug interactions with oral contraceptives." Clin Pharmacokinet, 18, p. 472-84
  27. D'Arcy PF (1986) "Drug interactions with oral contraceptives." Drug Intell Clin Pharm, 20, p. 353-62
  28. Notelovitz M, Tjapkes J, Ware M (1981) "Interaction between estrogen and dilantin in a menopausal woman." N Engl J Med, 304, p. 788-9
  29. (2001) "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories
  30. Strayhorn VA, Baciewicz AM, Self TH (1997) "Update on rifampin drug interactions, III." Arch Intern Med, 157, p. 2453-8
  31. Michalets EL (1998) "Update: clinically significant cytochrome P-450 drug interactions." Pharmacotherapy, 18, p. 84-112
  32. Back DJ, Breckenridge AM, Crawford FE, MacIver M, Orne ML, Rowe PH (1981) "Interindividual variation and drug interactions with hormonal steroid contraceptives." Drugs, 21, p. 46-61
  33. LeBel M, Masson E, Guilbert E, Colborn D, Paquet F, Allard S, Vallee F, Narang PK (1998) "Effects of rifabutin and rifampicin on the pharmacokinetics of ethinylestradiol and norethindrone." J Clin Pharmacol, 38, p. 1042-50
  34. Barditch-Crovo P, Trapnell CB, Ette E, et al. (1999) "The effects of rifampin and rifabutin on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive." Clin Pharmacol Ther, 65, p. 428-38
  35. Weisberg E (1999) "Interactions between oral contraceptives and antifungals antibacterials - Is contraceptive failure the result?." Clin Pharmacokinet, 36, p. 309-13
  36. Klosterskov Jensen P, Saano V, Haring P, Svenstrup B, Menge GP (1992) "Possible interaction between oxcarbazepine and an oral contraceptive." Epilepsia, 33, p. 1149-52
  37. Wilbur K, Ensom MHH (2000) "Pharmacokinetic drug interactions between oral contraceptives and second-generation anticonvulsants." Clin Pharmacokinet, 38, p. 355-65
  38. Durr D, Stieger B, KullakUblick GA, Rentsch KM, Steinert HC, Meier PJ, Fattinger K (2000) "St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4." Clin Pharmacol Ther, 68, p. 598-604
  39. Weaver K, Glasier A (1999) "Interaction between broad-spectrum antibiotics and the combined oral contraceptive pill: a literature review." Contraception, 59, p. 71-8
  40. Zachariassen RD (1994) "Loss of oral contraceptive efficacy by concurrent antibiotic administration." Women Health, 22, p. 17-26
  41. Dickinson BD, Altman RD, Nielsen NH, Sterling ML (2001) "Drug interactions between oral contraceptives and antibiotics." Obstet Gynecol, 98(5 Pt 1), p. 853-60
  42. (2003) "Unwanted pregnancy on self-medication with St John's wort despite hormonal contraception." Br J Clin Pharmacol, 55, p. 112-113
  43. Pfrunder A, Schiesser M, Gerber S, Haschke M, Bitzer J, Drewe J (2003) "Interaction of St John's wort with low-dose oral contraceptive therapy: a randomized controlled trial." Br J Clin Pharmacol, 56, p. 683-90
  44. Hall SD, Wang Z, Huang SM, et al. (2003) "The interaction between St John's wort and an oral contraceptive." Clin Pharmacol Ther, 74, p. 525-35
  45. Gorski JC, Hamman MA, Wang Z, Vasvada N, Huang S, Hall SD (2002) "The effect of St. John's wort on the efficacy of oral contraception." Clin Pharmacol Ther, 71, P25
  46. Schwarz UI, Buschel B, Kirch W (2001) "Failure of oral contraceptives because of St. John's wort." Eur J Clin Pharmacol, 57, A25
  47. Faculty of Sexual & Reproductive Healthcare (2016) "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception. file:///C:/Users/df033684/Downloads/ceuguidancedruginteractionshormonal.pdf"

Drug and food interactions

Major

acetaminophen food

Applies to: Fioricet (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: Fioricet (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: Fioricet (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

conjugated estrogens food

Applies to: conjugated estrogens

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.

References (2)
  1. Weber A, Jager R, Borner A, et al. (1996) "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception, 53, p. 41-7
  2. Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T (1995) "Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol." Eur J Drug Metab Pharmacokinet, 20, p. 219-24
Minor

caffeine food

Applies to: Fioricet (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.

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