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Drug Interactions between Dep Gynogen and Tagamet

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

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Interactions between your drugs

Minor

cimetidine estradiol

Applies to: Tagamet (cimetidine) and Dep Gynogen (estradiol)

Theoretically, pharmacologic effects of estrogens may be enhanced during treatment with cimetidine due to increased serum concentrations of endogenous estradiol. The mechanism is cimetidine inhibition of the 2-hydroxylation of estradiol. In nine healthy male volunteers, the mean percentage of estradiol 2-hydroxylation decreased by 25% during a cimetidine infusion (300 mg once followed by 50 mg/hr) and by nearly 40% following two weeks of oral cimetidine (800 mg twice a day), the latter accompanied by a 20% increase in serum estradiol concentration. The interaction was also demonstrated with a lower dosage of cimetidine (400 mg orally twice a day for one week). In another study, estradiol 2-hydroxylation decreased by nearly 30% in nine premenopausal women after one month of cimetidine (800 mg orally twice a day), but there was no change in serum estradiol levels (follicular phase). In contrast, estradiol 2-hydroxylation decreased by one-half and serum estradiol levels doubled in five postmenopausal women after one month of cimetidine treatment (600 mg orally twice a day for 2 weeks, followed by 1200 mg twice a day). The clinical significance of these changes is unknown. Ranitidine (150 mg twice a day) has been shown to have no effect on estradiol metabolism or serum levels.

References

  1. Galbraith RA, Michnovicz JJ "The oxidative metabolism of estradiol: inhibition by cimetidine." Trans Assoc Am Physicians 102 (1989): 44-54
  2. Galbraith RA, Michnovicz JJ "The effects of cimetidine on the oxidative metabolism of estradiol." N Engl J Med 321 (1989): 269-74
  3. Michnovicz JJ, Galbraith RA "Cimetidine inhibits catechol estrogen metabolism in women." Metabolism 40 (1991): 170-4

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Drug and food interactions

Minor

estradiol food

Applies to: Dep Gynogen (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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Minor

cimetidine food

Applies to: Tagamet (cimetidine)

Concurrent use of cimetidine and ethanol may result in increased ethanol concentrations. The mechanism appears to be due to inhibition of gastric alcohol dehydrogenase by cimetidine, leading to increased bioavailability of the alcohol and inhibition of hepatic metabolism of alcohol. The clinical significance of this interaction is limited. More importantly, patients requiring cimetidine for gastrointestinal disease should be counseled to avoid alcohol to prevent worsening of their disease. The other H-2 receptor antagonists appear to have minimal effects on the concentrations of alcohol.

References

  1. Feely J, Wood AJ "Effects of cimetidine on the elimination and actions of ethanol." JAMA 247 (1982): 2819-21
  2. Hansten PD "Effects of H2-receptor antagonists on blood alcohol levels." JAMA 267 (1992): 2469

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Minor

cimetidine food

Applies to: Tagamet (cimetidine)

Caffeine effects may be increased in patients also taking cimetidine. The mechanism may be due to decreased caffeine metabolism induced by cimetidine. Although adequate clinical data are lacking, a reduction in dose or elimination of caffeine may be needed if excess CNS stimulation is observed.

References

  1. "Product Information. Tagamet (cimetidine)." SmithKline Beecham PROD (2001):
  2. Broughton LJ, Rodgers HJ "Decreased systenuc clearance of caffeine due to cimetidine." Br J Clin Pharmacol 12 (1981): 155-9

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Minor

cimetidine food

Applies to: Tagamet (cimetidine)

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.

References

  1. Bendayan R, Sullivan JT, Shaw C, Frecker RC, Sellers EM "Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans." Eur J Clin Pharmacol 38 (1990): 165-9

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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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