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Drug Interactions between Estradot and Lufyllin-EPG

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

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Moderate

PHENobarbital estradiol

Applies to: Lufyllin-EPG (dyphylline / ephedrine / guaifenesin / phenobarbital) and Estradot (estradiol)

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response to estrogens and progestins should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the hormone dosage adjusted as necessary.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 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

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

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Minor

ePHEDrine dyphylline

Applies to: Lufyllin-EPG (dyphylline / ephedrine / guaifenesin / phenobarbital) and Lufyllin-EPG (dyphylline / ephedrine / guaifenesin / phenobarbital)

Ephedrine-methylxanthine combinations are used for the treatment of asthma but the efficacy of the combination has been questioned. This combination may lead to increased xanthine side effects. The mechanism is unknown, but may be related to synergistic pharmacologic effects. Patients using this combination should be closely monitored for side effects such as nausea, vomiting, tachycardia, nervousness, or insomnia. If side effects are noted, the dosage of the xanthine may need to be decreased.

References

  1. Weinberger M, Bronsky E, Bensch GW, Bock GN, Yecies JJ "Interaction of ephedrine and theophylline." Clin Pharmacol Ther 17 (1975): 585-92
  2. Sims JA, doPico GA, Reed CE "Bronchodilating effect of oral theophylline-ephedrine combination." J Allergy Clin Immunol 62 (1978): 15-21
  3. Tinkelman DG, Avner SE "Ephedrine therapy in asthmatic children. Clinical tolerance and absence of side effects." JAMA 237 (1977): 553-7
  4. Weinberger MM, Brousky EA "Evaluation of oral bronchodilator therapy in asthmatic children: bronchodilators in asthmatic children." J Pediatr 84 (1974): 421-7
  5. Badiei B, Faciane J, Sly M "Effect of throphylline, ephedrine and theri combination upon exercise-induced airway obstruction." Ann Allergy 35 (1975): 32-6
View all 5 references

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Drug and food interactions

Major

PHENobarbital food

Applies to: Lufyllin-EPG (dyphylline / ephedrine / guaifenesin / phenobarbital)

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

ePHEDrine food

Applies to: Lufyllin-EPG (dyphylline / ephedrine / guaifenesin / phenobarbital)

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

References

  1. Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res 1 (1979): 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther 11 (1970): 656
  3. "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc PROD (2001):
  4. "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals PROD (2001):
  5. "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals PROD (2001):
  6. "Product Information. Focalin (dexmethylphenidate)." Mikart Inc (2001):
  7. "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company (2002):
View all 7 references

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Minor

estradiol food

Applies to: Estradot (estradiol)

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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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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Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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