Chemical formula: C₂₀H₂₅NO₂ Molecular mass: 311.425 g/mol PubChem compound: 68861
Dienogest interacts in the following cases:
Substances increasing the clearance of sex hormones (diminished efficacy by enzyme-induction), e.g.: phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin, and products containing St. John’s wort (Hypericum perforatum).
Enzyme induction can already be observed after a few days of treatment. Maximum enzyme induction is generally seen within a few weeks After cessation of drug therapy enzyme induction may be sustained for about 4 weeks.
The effect of the CYP 3A4 inducer rifampicin was studied in healthy postmenopausal women. Coadministration of rifampicin with estradiol valerate/dienogest tablets led to significant decreases in steady state concentrations and systemic exposures of dienogest and estradiol. The systemic exposure of dienogest and estradiol at steady state, measured by AUC, were decreased by 83% and 44%, respectively.
Dienogest is a substrate of cytochrome P450 (CYP) 3A4.
Concomitant administration of strong CYP3A4 inhibitors can increase plasma concentrations of dienogest.
Coadministration with the strong CYP3A4 enzyme inhibitor ketoconazole resulted in a 2.9-fold increase of AUC (0-24h) at steady state for dienogest. Concomitant administration of the moderate inhibitor erythromycin increased the AUC (0-24h) of dienogest at steady state by 1.6-fold.
When co-administered with sex hormones, many combinations of HIV protease inhibitors and nonnucleoside reverse transcriptase inhibitors, including combinations with HCV inhibitors can increase or decrease plasma concentrations of the progestin. The net effect of these changes may be clinically relevant in some cases.
Based on the available data, ovulation is inhibited in the majority of patients during treatment with dienogest. However, dienogest is not a contraceptive.
If contraception is required a non-hormonal method should be used.
Based on available data, the menstrual cycle returns to normal within 2 months after cessation of treatment with dienogest.
Patients who have a history of depression should be carefully observed and the drug should be discontinued if the depression recurs to a serious degree.
Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation whilst taking dienogest.
Dienogest generally does not appear to affect blood pressure in normotensive women. However, if a sustained clinically significant hypertension develops during the use of dienogest, it is advisable to withdraw dienogest and treat the hypertension.
Recurrence of cholestatic jaundice and/or pruritus which occurred first during pregnancy or previous use of sex steroids necessitates the discontinuation of dienogest.
The use of dienogest in adolescents (12 to <18 years) over a treatment period of 12 months was associated with a decrease in bone mineral density (BMD) in the lumbar spine (L2-L4). The mean relative change in BMD from baseline to the end of treatment (EOT) was -1.2% with a range between -6% and 5% (IC 95%: -1.70% and -0.78%, n=103. Repeated measurement at 6 months after the EOT in a subgroup with decreased BMD values showed a trend towards recovery. (Mean relative change from baseline: -2.3% at EOT and -0.6% at 6 months after EOT with a range between -9% and 6% (IC 95%: -1.20% and 0.06% (n=60) Loss of BMD is of particular concern during adolescence and early adulthood, a critical period of bone accretion. It is unknown if BMD decrease in this population will reduce peak bone mass and increase the risk for fracture in later life.
In patients who are at an increased risk of osteoporosis a careful risk-benefit assessment should be performed before starting dienogest because endogenous estrogen levels are moderately decreased during treatment with dienogest.
Adequate intake of calcium and vitamin D, whether from the diet or from supplements, is important for bone health in women of all ages.
Dienogest may have a slight effect on peripheral insulin resistance and glucose tolerance. Diabetic women, especially those with a history of gestational diabetes mellitus, should be carefully observed while taking dienogest.
There is limited data from the use of dienogest in pregnant women.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.
Dienogest must not be administered to pregnant women because there is no need to treat endometriosis during pregnancy.
Treatment with dienogest during lactation is not recommended.
It is unknown wheter dienogest is excreted in human milk. Data in animals have shown excretion of dienogest in rat milk.
A decision must be made whether to discontinue breast-feeding or to abstain from dienogest therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Based on the available data, ovulation is inhibited in the majority of patients during treatment with dienogest. However, dienogest is not a contraceptive.
If contraception is required a non-hormonal method should be used.
Based on available data, the menstrual cycle returns to normal within 2 months after cessation of treatment with dienogest.
No effects on the ability to drive and use machines have been observed in users of products containing dienogest.
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