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Drug Interactions between ethinyl estradiol / ethynodiol and Farbital

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

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Moderate

ethinyl estradiol butalbital

Applies to: ethinyl estradiol / ethynodiol and Farbital (aspirin / butalbital / caffeine)

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with a barbiturate may reduce the efficacy of contraceptive hormones. There have been numerous case reports of menstrual abnormalities (e.g., breakthrough bleeding, amenorrhea, irregular menses) and unintended pregnancy occurring in women who received oral contraceptives with phenobarbital. In a study of four women treated chronically with a contraceptive pill containing 50 mcg of ethinyl estradiol, coadministration with phenobarbital (30 mg twice a day) was associated with breakthrough bleeding and a greater than 60% reduction in plasma ethinyl estradiol concentration in two of the women. The interaction stems from accelerated clearance of contraceptive hormones as well as decreased plasma concentrations of unbound (active) hormones due to induction of hepatic CYP450 enzymatic activity and enhancement of hormone-binding globulin capacity by phenobarbital. Since all barbiturates are believed to possess enzyme-inducing capabilities, the interaction should be expected with agents in the class other than phenobarbital.

MANAGEMENT: Women using hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with barbiturates. Alternative or additional methods of birth control should be used during and for at least one week after short-term and 4 weeks after long-term (greater than 4 weeks) barbiturate therapy. No precautions or recommendations are available for women using hormone-releasing intrauterine systems, but a significant interaction with these systems is thought to be unlikely due to their local action. Injectable progestin-only contraceptives are also thought to be unaffected by barbiturates. Input from a gynecologist or similar expert on adequate contraception, including emergency contraception, should be sought as needed.

References

  1. Baciewicz AM "Oral contraceptive drug interactions." Ther Drug Monit 7 (1985): 26-35
  2. Mumford JP "Letter: Drugs affecting oral contraceptives." Br Med J 2 (1974): 333-4
  3. Back DJ, Bates M, Bowden A, et al. "The interaction of phenobarbital and other anticonvulsants with oral contraceptive steroid therapy." Contraception 22 (1980): 495-503
  4. Dossetor J "Drug interactions with oral contraceptives." Br Med J 4 (1975): 467-8
  5. Furlan AJ, Rothner AD "Anti-epileptic drugs and failure of oral contraceptives." Lancet 1 (1974): 1113
  6. Coulam CB, Annegers JF "Do anticonvulsants reduce the efficacy of oral contraceptives?" Epilepsia 20 (1979): 519-26
  7. Szoka PR, Edgren RA "Drug interactions with oral contraceptives: compilation and analysis of an adverse experience report database." Fertil Steril 49 (1988): s31-8
  8. Mattson RH, Cramer JA, Darney PD, Naftolin F "Use of oral contraceptives by women with epilepsy." JAMA 256 (1986): 238-40
  9. Laengner H, Detering K "Letter: Anti-epileptic drugs and failure of oral contraceptives." Lancet 2 (1974): 600
  10. Curran MA "Drug interactions with the pill." Med J Aust 144 (1986): 670-1
  11. Back DJ, Orme ML "Pharmacokinetic drug interactions with oral contraceptives." Clin Pharmacokinet 18 (1990): 472-84
  12. D'Arcy PF "Drug interactions with oral contraceptives." Drug Intell Clin Pharm 20 (1986): 353-62
  13. Kleier DJ, Tucker JE "Oral contraceptive failure secondary to dentally prescribed drugs: fact or fiction?" J Colo Dent Assoc 66 (1987): 5-6
  14. Back DJ, Breckenridge AM, Crawford FE, MacIver M, Orne ML, Rowe PH "Interindividual variation and drug interactions with hormonal steroid contraceptives." Drugs 21 (1981): 46-61
  15. Shane-McWorter L, Cerveny JD, MacFarlane LL, Osborn C "Enhanced metabolism of levonorgestrel during phenobarbital treatment and resultant pregnancy." Pharmacotherapy 18 (1998): 1360-4
  16. Haukkamaa M "Contraception by Norplant subdermal capsules is not reliable in epileptic patients on anticonvulsant treatment." Contraception 33 (1986): 559-65
  17. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories PROD (2001):
  18. Back DJ, Grimmer SF, Orme ML, Proudlove D, Mann RD, Breckenridge AM "Evaluation of Committee on Safety of Medicines yellow card reports on oral contraceptive-drug interactions with anticonvulsants and antibiotics." Br J Clin Pharmacol 25 (1988): 527-32
  19. O'Brien MD, Guillebaud J "Contraception for women with epilepsy." Epilepsia 47 (2006): 1419-22
  20. Faculty of Sexual & Reproductive Healthcare "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception. file:///C:/Users/df033684/Downloads/ceuguidancedruginteractionshormonal.pdf" (2016):
View all 20 references

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Moderate

butalbital ethynodiol

Applies to: Farbital (aspirin / butalbital / caffeine) and ethinyl estradiol / ethynodiol

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with a barbiturate may reduce the efficacy of contraceptive hormones. There have been numerous case reports of menstrual abnormalities (e.g., breakthrough bleeding, amenorrhea, irregular menses) and unintended pregnancy occurring in women who received oral contraceptives with phenobarbital. In a study of four women treated chronically with a contraceptive pill containing 50 mcg of ethinyl estradiol, coadministration with phenobarbital (30 mg twice a day) was associated with breakthrough bleeding and a greater than 60% reduction in plasma ethinyl estradiol concentration in two of the women. The interaction stems from accelerated clearance of contraceptive hormones as well as decreased plasma concentrations of unbound (active) hormones due to induction of hepatic CYP450 enzymatic activity and enhancement of hormone-binding globulin capacity by phenobarbital. Since all barbiturates are believed to possess enzyme-inducing capabilities, the interaction should be expected with agents in the class other than phenobarbital.

MANAGEMENT: Women using hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with barbiturates. Alternative or additional methods of birth control should be used during and for at least one week after short-term and 4 weeks after long-term (greater than 4 weeks) barbiturate therapy. No precautions or recommendations are available for women using hormone-releasing intrauterine systems, but a significant interaction with these systems is thought to be unlikely due to their local action. Injectable progestin-only contraceptives are also thought to be unaffected by barbiturates. Input from a gynecologist or similar expert on adequate contraception, including emergency contraception, should be sought as needed.

References

  1. Baciewicz AM "Oral contraceptive drug interactions." Ther Drug Monit 7 (1985): 26-35
  2. Mumford JP "Letter: Drugs affecting oral contraceptives." Br Med J 2 (1974): 333-4
  3. Back DJ, Bates M, Bowden A, et al. "The interaction of phenobarbital and other anticonvulsants with oral contraceptive steroid therapy." Contraception 22 (1980): 495-503
  4. Dossetor J "Drug interactions with oral contraceptives." Br Med J 4 (1975): 467-8
  5. Furlan AJ, Rothner AD "Anti-epileptic drugs and failure of oral contraceptives." Lancet 1 (1974): 1113
  6. Coulam CB, Annegers JF "Do anticonvulsants reduce the efficacy of oral contraceptives?" Epilepsia 20 (1979): 519-26
  7. Szoka PR, Edgren RA "Drug interactions with oral contraceptives: compilation and analysis of an adverse experience report database." Fertil Steril 49 (1988): s31-8
  8. Mattson RH, Cramer JA, Darney PD, Naftolin F "Use of oral contraceptives by women with epilepsy." JAMA 256 (1986): 238-40
  9. Laengner H, Detering K "Letter: Anti-epileptic drugs and failure of oral contraceptives." Lancet 2 (1974): 600
  10. Curran MA "Drug interactions with the pill." Med J Aust 144 (1986): 670-1
  11. Back DJ, Orme ML "Pharmacokinetic drug interactions with oral contraceptives." Clin Pharmacokinet 18 (1990): 472-84
  12. D'Arcy PF "Drug interactions with oral contraceptives." Drug Intell Clin Pharm 20 (1986): 353-62
  13. Kleier DJ, Tucker JE "Oral contraceptive failure secondary to dentally prescribed drugs: fact or fiction?" J Colo Dent Assoc 66 (1987): 5-6
  14. Back DJ, Breckenridge AM, Crawford FE, MacIver M, Orne ML, Rowe PH "Interindividual variation and drug interactions with hormonal steroid contraceptives." Drugs 21 (1981): 46-61
  15. Shane-McWorter L, Cerveny JD, MacFarlane LL, Osborn C "Enhanced metabolism of levonorgestrel during phenobarbital treatment and resultant pregnancy." Pharmacotherapy 18 (1998): 1360-4
  16. Haukkamaa M "Contraception by Norplant subdermal capsules is not reliable in epileptic patients on anticonvulsant treatment." Contraception 33 (1986): 559-65
  17. "Product Information. Norplant System (levonorgestrel)." Wyeth-Ayerst Laboratories PROD (2001):
  18. Back DJ, Grimmer SF, Orme ML, Proudlove D, Mann RD, Breckenridge AM "Evaluation of Committee on Safety of Medicines yellow card reports on oral contraceptive-drug interactions with anticonvulsants and antibiotics." Br J Clin Pharmacol 25 (1988): 527-32
  19. O'Brien MD, Guillebaud J "Contraception for women with epilepsy." Epilepsia 47 (2006): 1419-22
  20. Faculty of Sexual & Reproductive Healthcare "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception. file:///C:/Users/df033684/Downloads/ceuguidancedruginteractionshormonal.pdf" (2016):
View all 20 references

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Minor

aspirin caffeine

Applies to: Farbital (aspirin / butalbital / caffeine) and Farbital (aspirin / butalbital / caffeine)

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

References

  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet 11 (1986): 71-6

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Drug and food interactions

Major

butalbital food

Applies to: Farbital (aspirin / 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

aspirin food

Applies to: Farbital (aspirin / butalbital / caffeine)

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

References

  1. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn PROD (2002):

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Minor

ethinyl estradiol food

Applies to: ethinyl estradiol / ethynodiol

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

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

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Minor

caffeine food

Applies to: Farbital (aspirin / 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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Minor

ethinyl estradiol food

Applies to: ethinyl estradiol / ethynodiol

The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition. Consider counseling women about this interaction which is unpredictable.

References

  1. Hobbes J, Boutagy J, Shenfield GM "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther 38 (1985): 371-80

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Minor

ethynodiol food

Applies to: ethinyl estradiol / ethynodiol

The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition. Consider counseling women about this interaction which is unpredictable.

References

  1. Hobbes J, Boutagy J, Shenfield GM "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther 38 (1985): 371-80

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Minor

aspirin food

Applies to: Farbital (aspirin / butalbital / caffeine)

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.

References

  1. Yoovathaworn KC, Sriwatanakul K, Thithapandha A "Influence of caffeine on aspirin pharmacokinetics." Eur J Drug Metab Pharmacokinet 11 (1986): 71-6

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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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