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Drug Interactions between ethinyl estradiol / ethynodiol and pioglitazone

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

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Interactions between your drugs

Minor

ethinyl estradiol pioglitazone

Applies to: ethinyl estradiol / ethynodiol and pioglitazone

Coadministration with another thiazolidinedione, troglitazone, has been shown to decrease the plasma concentrations of contraceptive hormones. The proposed mechanism is induction of hormone metabolism via CYP450 3A4. In 15 healthy female subjects, troglitazone (60 mg once daily for 3 weeks) decreased the mean steady-state peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of ethinyl estradiol and norethindrone (35 mcg-1 mg) by approximately 30% each compared to administration of the contraceptive alone. Four subjects experienced breakthrough bleeding during the cycle with troglitazone. There are no data on the use of contraceptive hormones with pioglitazone. Because pioglitazone may be a weak inducer of CYP450 3A4, product labeling recommends additional caution in women requiring contraception. However, some studies have reported no significant effect of pioglitazone on CYP450 3A4. Rosiglitazone labeling states that the drug given in a dosage of 4 mg twice daily had no clinically relevant effect on the pharmacokinetics of oral contraceptives (ethinyl estradiol and norethindrone). Intrauterine systems are unlikely to be significantly affected because of their local action.

References

  1. (2001) "Product Information. Avandia (rosiglitazone)." SmithKline Beecham
  2. (2001) "Product Information. Actos (pioglitazone)." Takeda Pharmaceuticals America
  3. Loi CM, Stern R, Koup JR, Vassos AB, Knowlton P, Sedman AJ (1999) "Effect of troglitazone on the pharmacokinetics of an oral contraceptive agent." J Clin Pharmacol, 39, p. 410-7
  4. Glazer NB, Cheatham WW (2001) "Thiazolidinediones for type 2 diabetes - No evidence exists that pioglitazone induces hepatic cytochrome P450 isoform CYP3A4." Br Med J, 322, p. 235-6
  5. Nowak SN, Edwards DJ, Clarke A, Anderson GD, Jaber LA (2002) "Pioglitazone: effect on CYP3A4 activity." J Clin Pharmacol, 42, p. 1299-302
View all 5 references

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Minor

ethynodiol pioglitazone

Applies to: ethinyl estradiol / ethynodiol and pioglitazone

Coadministration with another thiazolidinedione, troglitazone, has been shown to decrease the plasma concentrations of contraceptive hormones. The proposed mechanism is induction of hormone metabolism via CYP450 3A4. In 15 healthy female subjects, troglitazone (60 mg once daily for 3 weeks) decreased the mean steady-state peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of ethinyl estradiol and norethindrone (35 mcg-1 mg) by approximately 30% each compared to administration of the contraceptive alone. Four subjects experienced breakthrough bleeding during the cycle with troglitazone. There are no data on the use of contraceptive hormones with pioglitazone. Because pioglitazone may be a weak inducer of CYP450 3A4, product labeling recommends additional caution in women requiring contraception. However, some studies have reported no significant effect of pioglitazone on CYP450 3A4. Rosiglitazone labeling states that the drug given in a dosage of 4 mg twice daily had no clinically relevant effect on the pharmacokinetics of oral contraceptives (ethinyl estradiol and norethindrone). Intrauterine systems are unlikely to be significantly affected because of their local action.

References

  1. (2001) "Product Information. Avandia (rosiglitazone)." SmithKline Beecham
  2. (2001) "Product Information. Actos (pioglitazone)." Takeda Pharmaceuticals America
  3. Loi CM, Stern R, Koup JR, Vassos AB, Knowlton P, Sedman AJ (1999) "Effect of troglitazone on the pharmacokinetics of an oral contraceptive agent." J Clin Pharmacol, 39, p. 410-7
  4. Glazer NB, Cheatham WW (2001) "Thiazolidinediones for type 2 diabetes - No evidence exists that pioglitazone induces hepatic cytochrome P450 isoform CYP3A4." Br Med J, 322, p. 235-6
  5. Nowak SN, Edwards DJ, Clarke A, Anderson GD, Jaber LA (2002) "Pioglitazone: effect on CYP3A4 activity." J Clin Pharmacol, 42, p. 1299-302
View all 5 references

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Drug and food interactions

Moderate

pioglitazone food

Applies to: pioglitazone

GENERALLY AVOID: Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes. Hypoglycemia most frequently occurs during acute consumption of alcohol. Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise. The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia. Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion. By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia. Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes. A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

MANAGEMENT: Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis. Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan. Alcohol should not be consumed on an empty stomach or following exercise.

References

  1. Jerntorp P, Almer LO (1981) "Chlorpropamide-alcohol flushing in relation to macroangiopathy and peripheral neuropathy in non-insulin dependent diabetes." Acta Med Scand, 656, p. 33-6
  2. Jerntorp P, Almer LO, Holin H, et al. (1983) "Plasma chlorpropamide: a critical factor in chlorpropamide-alcohol flush." Eur J Clin Pharmacol, 24, p. 237-42
  3. Barnett AH, Spiliopoulos AJ, Pyke DA, et al. (1983) "Metabolic studies in chlorpropamide-alcohol flush positive and negative type 2 (non-insulin dependent) diabetic patients with and without retinopathy." Diabetologia, 24, p. 213-5
  4. Hartling SG, Faber OK, Wegmann ML, Wahlin-Boll E, Melander A (1987) "Interaction of ethanol and glipizide in humans." Diabetes Care, 10, p. 683-6
  5. (2002) "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals
  6. (2002) "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals
  7. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  8. Skillman TG, Feldman JM (1981) "The pharmacology of sulfonylureas." Am J Med, 70, p. 361-72
  9. (2002) "Position Statement: evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes related complications. American Diabetes Association." Diabetes Care, 25(Suppl 1), S50-S60
  10. Cerner Multum, Inc. "UK Summary of Product Characteristics."
View all 10 references

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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. (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

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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 (1985) "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther, 38, p. 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 (1985) "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther, 38, p. 371-80

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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.

Further information

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

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