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Drug Interactions between Femsept and SGard

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

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Interactions between your drugs

Moderate

estradiol melatonin

Applies to: Femsept (estradiol) and SGard (melatonin)

MONITOR: Coadministration with inhibitors of CYP450 1A2 may substantially increase the plasma concentrations of melatonin. Data from available studies suggest that melatonin is primarily metabolized by CYP450 1A2, with possible contribution from CYP450 2C19 and 2C9. Coadministration of fluvoxamine, a potent CYP450 1A2 inhibitor that also inhibits CYP450 2C19 and 2C9, increased melatonin systemic exposure (AUC) by 17-fold and maximum plasma concentration (Cmax) by 12-fold. Contraceptives containing ethinyl estradiol, which can inhibit CYP450 1A2, may lead to a 4- to 5-fold increase in melatonin concentration. The risk of this interaction may be less likely to occur with estrogen products that have limited systemic absorption (e.g., vaginal, topical products).

MANAGEMENT: Caution is advised when melatonin is used concomitantly with CYP450 1A2 inhibitors. Patients should be monitored closely for adverse effects such as excessive drowsiness, headache, lethargy, dizziness, irritability, nervousness, restlessness, anxiety, abdominal pain, and dyspepsia.

References

  1. Cerner Multum, Inc. "Australian Product Information." O 0
  2. "Product Information. Melatonin (ARX) (melatonin)." Apotex Pty Ltd (2023):

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Drug and food interactions

Moderate

melatonin food

Applies to: SGard (melatonin)

MONITOR: Oral caffeine may significantly increase the bioavailability of melatonin. The proposed mechanism is inhibition of CYP450 1A2 first-pass metabolism. After administration of melatonin 6 mg and caffeine 200 mg orally (approximately equivalent to 1 large cup of coffee) to 12 healthy subjects, the mean peak plasma concentration (Cmax) of melatonin increased by 137% and the area under the concentration-time curve (AUC) increased by 120%. The metabolic inhibition was greater in nonsmokers (n=6) than in smokers (n=6). The greatest effect was seen in subjects with the *1F/*1F genotype (n=7), whose melatonin Cmax increased by 202%. The half-life did not change significantly. The clinical significance of this interaction is unknown.

According to some authorities, alcohol may reduce the effect of melatonin on sleep. The mechanism of this interaction is not fully understood.

In addition, CYP450 1A2 inducers like cigarette smoking may reduce exogenous melatonin plasma levels. In a small clinical trial (n=8), habitual smokers had their melatonin plasma levels measured two times, each after a single oral dose of 25 mg of melatonin. They had smoked prior to the first measurement but had not smoked for 7 days prior to the second. Cigarette smoking significantly reduced melatonin plasma exposure (AUC) as compared to melatonin levels after 7 days of smoking abstinence (7.34 +/- 1.85 versus 21.07 +/- 7.28 nmol/L*h, respectively).

MANAGEMENT: Caution and monitoring are recommended if melatonin is used with inhibitors of CYP450 1A2 like caffeine or inducers of CYP450 1A2 like cigarette smoking. Consumption of alcohol should be avoided when taking melatonin.

References

  1. Hartter S, Nordmark A, Rose DM, Bertilsson L, Tybring G, Laine K "Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity." Br J Clin Pharmacol 56 (2003): 679-682
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Ursing C, Bahr CV, Brismar K, Rojdmark S "Influence of cigarette smoking on melatonin levels in man" Eur J Clin Pharmacol 61 (2005): 197-201

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Minor

estradiol food

Applies to: Femsept (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.

See also

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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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