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Drug Interactions between Estinyl and Zanaflex

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

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Interactions between your drugs

Major

ethinyl estradiol tiZANidine

Applies to: Estinyl (ethinyl estradiol) and Zanaflex (tizanidine)

GENERALLY AVOID: Coadministration with oral contraceptives may significantly increase the plasma concentrations and pharmacologic effects of tizanidine. The proposed mechanism is inhibition of tizanidine metabolism via CYP450 1A2. Retrospective evaluation of population pharmacokinetic data following single- and multiple-dose administration of tizanidine revealed an approximately 50% decrease in the clearance of tizanidine in women receiving oral contraceptives compared to women not receiving oral contraceptives. In a study of 30 healthy volunteers administered a single 4 mg dose of tizanidine, mean peak plasma concentration (Cmax) of tizanidine was 3.0 times higher and mean area under the plasma concentration-time curve (AUC) was 3.9 times greater in women using an oral contraceptive containing ethinyl estradiol and gestodene than in women not on the contraceptive. In one contraceptive user, the tizanidine AUC exceeded the mean AUC of the control subjects by nearly 20 times. There were no significant differences in the elimination half-life or time to peak concentration in plasma (Tmax) of tizanidine between the groups. Tizanidine to metabolite ratios in plasma and urine were 2 to 10 times higher in the contraceptive users than in control subjects, and the excretion of unchanged tizanidine into urine was on average 3.8 times greater in the contraceptive group. In addition, both the systolic and diastolic blood pressures were lowered by tizanidine more in the contraceptive users (29 mmHg and 21 mm Hg, respectively) than in the control subjects (17 mmHg and 13 mmHg, respectively). The interaction has also been reported with other CYP450 1A2 inhibitors such as fluvoxamine, ciprofloxacin, and rofecoxib.

MANAGEMENT: The use of tizanidine in combination with oral contraceptives or other CYP450 1A2 inhibitors should generally be avoided. Caution is advised if concurrent use is clinically necessary. Dosage adjustments may be required in patients who experience excessive adverse effects of tizanidine such as drowsiness, dizziness, lightheadedness, hypotension, bradycardia, or syncope.

References

  1. (2001) "Product Information. Zanaflex (tizanidine)." Acorda Therapeutics
  2. (2001) "Product Information. Vioxx (rofecoxib)." Merck & Co., Inc
  3. Granfors MT, Backman JT, Laitila J, Neuvonen PJ (2004) "Tizanidine is mainly metabolized by cytochrome P450 1A2 in vitro." Br J Clin Pharmacol, 57, p. 349-53
  4. Granfors MT, Backman JT, Neuvonen M, Ahonen J, Neuvonen PJ (2004) "Fluvoxamine drastically increases concentrations and effects of tizanidine: A potentially hazardous interaction." Clin Pharmacol Ther, 75, p. 331-41
  5. Momo K, Doki K, Hosono H, Homma M, Kohda Y (2004) "Drug interaction of tizanidine and fluvoxamine." Clin Pharmacol Ther, 76, p. 509-10
  6. Granfors MT, Backman JT, Neuvonen M, Neuvonen PJ (2004) "Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism." Clin Pharmacol Ther, 76, p. 598-606
  7. Granfors MT, Backman JT, Laitila J, Neuvonen PJ (2005) "Oral contraceptives containing ethinyl estradiol and gestodene markedly increase plasma concentrations and effects of tizanidine by inhibiting cytochrome P450 1A2." Clin Pharmacol Ther, 78, p. 400-11
View all 7 references

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Drug and food interactions

Minor

ethinyl estradiol food

Applies to: Estinyl (ethinyl 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. (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: Estinyl (ethinyl estradiol)

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.