DIENOSIS TABLET

Indications

• Endometriosis
• Management of symptoms associated with female sex hormone-responsive conditions
• Treatment of conditions related to excessive androgen activity, such as acne and hirsutism

Dosage

Adults: The recommended adult

Mechanism of action

Dienogest acts as an agonist at the progesterone receptor (PR) with a weak affinity comparable to that of progesterone, yet it exhibits a potent progestagenic effect within the endometrium, inducing endometrial atrophy with prolonged use. It reduces endogenous oestradiol production, thereby suppressing its trophic effects on both eutopic and ectopic endometrium. Additionally, dienogest displays antagonistic activity at androgen receptors, which helps improve symptoms of androgen excess.

Pharmacodynamics

Dienogest exhibits a strong progestagenic effect that leads to endometrial atrophy after extended use. It mediates antiandrogenic effects equivalent to about one third of cyproterone acetate's potency. A dose of 2 mg can inhibit ovarian follicle growth and maintain low progesterone levels, while also directly inhibiting ovulation at a dose of 1 mg/kg. Clinical trials have demonstrated its efficacy in reducing symptoms and lesions associated with endometriosis. Dienogest does not possess antiestrogenic activity and instead induces hypoestrogenic effects by decreasing the expression of estrogen receptors.

Pharmacokinetics

Dienogest is well absorbed after oral administration. It undergoes extensive hepatic metabolism, primarily via cytochrome P450 enzymes. The drug's half-life is approximately 9 to 10 hours, allowing for once-daily dosing. It is eliminated in urine and feces, with a significant portion being excreted as metabolites. The pharmacokinetics may be affected by co-administration with certain drugs, which can either increase or decrease its exposure.

Contra-indications

• Known hypersensitivity to dienogest or any of its components
• Active venous thromboembolism
• History of severe liver disease
• Hormone-dependent malignant tumors

Adverse effects

• Alopecia
• Breast abnormalities
• Dizziness
• Fatigue
• Gastrointestinal discomfort
• Headaches
• Nausea
• Pelvic pain
• Skin reactions
• Uterine disorders
• Vulvovaginal disorders
• Weight changes

Interactions

• Dronedarone: Unknown (increases exposure)
• Cobicistat: Unknown (increases exposure)
• Crizotinib: Unknown (increases exposure)
• Idelalisib: Unknown (increases exposure)
• Imatinib: Unknown (increases exposure)
• Letermovir: Unknown (increases exposure)
• Mitotane: Unknown (decreases exposure)
• Nilotinib: Unknown (increases exposure)
• Erythromycin: Unknown (increases exposure)
• Rifampicin: Unknown (decreases exposure)

Precautions

• Consider alternative therapies in patients with a history of thromboembolic disorders
• Monitor for signs of liver dysfunction
• Assess risk factors for hormone-dependent tumors

Pregnancy

Dienogest is contraindicated during pregnancy as it may adversely affect fetal development.

Breast-feeding

Dienogest is excreted in breast milk; caution is advised when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Tablets
• Capsules

Mechanism of action

Dienogest acts as an agonist at the progesterone receptor (PR) with weak affinity that is comparable to that of progesterone but has a very potent progestagenic effect in the endometrium, causing endometrial atrophy after prolonged use. It promotes antiproliferative, immunologic and antiangiogenic effects on endometrial tissue. Dienogest reduces the level of endogenous production of oestradiol and thereby suppressing the trophic effects of oestradiol on both the eutopic and ectopic endometrium. Continous administration of dienogest results in hyperprogestogenic and moderately hypoestrogenic endocrine environment, which causes initial decidualization of endometrial tissue. It is an antagonist at androgen receptors, improve androgenic symptoms such as acne and hirsutism.

Pharmacodynamics

Dienogest exhibits a very potent progestagenic effect in the endometrium, and causes endometrial atrophy after prolonged use . It also mediates an antiandrogenic effect that is equivalent to approximately one third that of cyproterone acetate. A dose of 2 mg inhibits the growth of ovarian follicles at 10 mm and maintains the concentration of progesterone at a low level, but has a weak inhibitory effect on FSH and LH. 1mg/kg of dienogest also directly inhibits ovulation. In clinical trials composing of patients with endometriosis, dienogest therapy effectively reduced painful symptoms and endometriotic lesions associated with the disorder. Dienogest displays no antiestrogenic activity as it activate neither estrogen receptor (ER) α nor ERβ, and causes hypoestrogenic effects instead as it is shown to decrease the relative expressions of ERβ and ERα. It has no glucocorticoid or mineralocorticoid effects. In combined oral contraceptive pills (COCP) with ethinyloestradiol, dienogest conjuction therapy effectively reduces the symptoms of acne and hirsutism, as well as improving excessively heavy or prolonged menstrual bleeding.