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Drug Interactions between metoprolol and Zovia 1/50E

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

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Interactions between your drugs

Moderate

metoprolol ethinyl estradiol

Applies to: metoprolol and Zovia 1 / 50E (ethinyl estradiol / ethynodiol)

MONITOR: Oral contraceptives containing ethinyl estradiol may interfere with the first-pass metabolism of certain beta-blockers and increase their plasma concentrations. In one study, young, healthy female subjects receiving a low-dose ethinyl estradiol oral contraceptive (OC) demonstrated higher plasma levels of metoprolol (100 mg), oxprenolol (80 mg), and propranolol (80 mg) following single-dose administration than control subjects who were not receiving an OC. Specifically, mean metoprolol peak plasma concentration (Cmax) and systemic exposure (AUC) were 36% and 71% higher, respectively, in OC users (n=12) than in non-users (n=11); mean oxprenolol Cmax and AUC were 6% and 26% higher, respectively, in OC users (n=7) than in non-users (n=8); and mean propranolol Cmax and AUC were 19% and 42% higher, respectively, in OC users (n=7) than in non-users (n=8). Only the difference in metoprolol AUC reached statistical significance, although the difference in propranolol AUC failed to reach significance by only a narrow margin.

MANAGEMENT: Pharmacologic effects including blood pressure and heart rate changes should be monitored more closely when metoprolol, oxprenolol, and propranolol are coadministered with ethinyl estradiol oral contraceptives, and dosage adjustments made as necessary.

References

  1. Kendall MJ, Quarterman CP, Jack DB, Beeley L (1982) "Metoprolol pharmacokinetics and the oral contraceptive pill." Br J Clin Pharmacol, 14, p. 120-2
  2. Kendall MJ, Jack DB, Quarterman CP, Smith SR, Zaman R (1984) "Beta-adrenoceptor blocker pharmacokinetics and the oral contraceptive pill." Br J Clin Pharmacol, 17, s87-9
  3. Jack DB, Quarterman CP, Zaman R, Kendall MJ (1982) "Variability of beta-blocker pharmacokinetics in young volunteers." Eur J Clin Pharmacol, 23, p. 37-42
  4. (2002) "Product Information. Tenormin (atenolol)." ICN Pharmaceuticals Inc
  5. (2002) "Product Information. Corgard (nadolol)." Bristol-Myers Squibb
  6. (2001) "Product Information. Cartrol (carteolol)." Abbott Pharmaceutical
  7. (2001) "Product Information. Betapace (sotalol)." Berlex Laboratories
  8. Seffart G ed. (1991) "Drug Dosage in Renal Insufficiency." Dordrecht, South Holland, : Kluwer Academic Publishers
View all 8 references

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Drug and food interactions

Moderate

metoprolol food

Applies to: metoprolol

ADJUST DOSING INTERVAL: The bioavailability of metoprolol may be enhanced by food.

MANAGEMENT: Patients may be instructed to take metoprolol at the same time each day, preferably with or immediately following meals.

References

  1. (2001) "Product Information. Lopressor (metoprolol)." Novartis Pharmaceuticals
  2. Darcy PF (1995) "Nutrient-drug interactions." Adverse Drug React Toxicol Rev, 14, p. 233-54

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Moderate

metoprolol food

Applies to: metoprolol

ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers. The exact mechanism of interaction is unknown. In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively. The elimination half-life increased by 44%. Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone. However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments. The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.

MANAGEMENT: It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours. Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.

References

  1. Kirch W, Schafer-Korting M, Axthelm T, Kohler H, Mutschler E (1981) "Interaction of atenolol with furosemide and calcium and aluminum salts." Clin Pharmacol Ther, 30, p. 429-35

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Minor

ethinyl estradiol food

Applies to: Zovia 1 / 50E (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: Zovia 1 / 50E (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: Zovia 1 / 50E (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

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