Dienogest is indicated for the treatment of endometriosis. It belongs to the class of medicines known as progestins. Progestins reduce the effects of estrogen on tissues such as the endometrium and breast tissue. By suppressing the growth-promoting effect of estrogen on the endometrium, Dienogest helps reduce pelvic pain associated with endometriosis.

Dienogest acts as an agonist at the progesterone receptor (PR) with relatively weak binding affinity similar to progesterone, but it exerts a strong progestogenic effect on the endometrium. Prolonged use can lead to endometrial atrophy. It has antiproliferative, immunologic, and antiangiogenic effects on endometrial tissue. Dienogest reduces endogenous estradiol production, thereby suppressing the trophic effects of estradiol on both eutopic and ectopic endometrium. Continuous administration creates a hyperprogestogenic and moderately hypoestrogenic endocrine environment, which initially causes decidualization of endometrial tissue. Dienogest also acts as an antagonist at androgen receptors and may improve androgen-related symptoms such as acne and hirsutism.

Tablet-taking can be started on any day of the menstrual cycle. The dosage of Dienogest is 2 mg daily without any break, taken preferably at the same time each day with some liquid as needed. Tablet must be taken continuously without regard to vaginal bleeding. When a pack is finished, the next one should be started without interruption.

In the event of missed tablet(s), the woman should take 2 mg only, as soon as she remembers, and should then continue the next day to take the tablet at her usual time. A tablet not absorbed due to vomiting or diarrhea should likewise be replaced by 2 mg.

Progestogens including Dienogest are mainly metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme system. Therefore, medications that induce or inhibit CYP3A4 may alter the metabolism of Dienogest. Known CYP3A4 inhibitors such as azole antifungals (e.g. ketoconazole, itraconazole, fluconazole), cimetidine, verapamil, macrolide antibiotics (e.g. erythromycin, clarithromycin, roxithromycin), diltiazem, protease inhibitors (e.g. ritonavir, saquinavir, indinavir, nelfinavir), and antidepressants (e.g. nefazodone, fluvoxamine, fluoxetine) may increase plasma concentrations of progestogens and increase the risk of adverse reactions.

Dienogest should not be used in patients with hypersensitivity to Dienogest or any of its excipients. It is contraindicated in the following conditions:

• Active venous thromboembolic disorders
• Arterial and cardiovascular diseases such as myocardial infarction, cerebrovascular accident, or ischemic heart disease
• Diabetes mellitus with vascular complications
• Severe hepatic disease while liver function has not returned to normal
• Current or previous liver tumors (benign or malignant)
• Known or suspected sex hormone-dependent malignancies
• Undiagnosed vaginal bleeding

Undesirable effects are more commonly observed during the first few months of Dienogest therapy and usually decrease over time. Frequently reported adverse reactions include breast discomfort (5.4%), depressed mood (5.1%), and acne (5.1%).

• Nervous System Disorders: Headache, migraine
• Cardiac Disorders: Uncommon – circulatory disorders, palpitations
• Vascular Disorders: Uncommon – hypotension
• Gastrointestinal Disorders: Nausea, abdominal pain, flatulence
• Metabolism and Nutrition Disorders: Weight gain (3.6%)
• Psychiatric Disorders: Depressed mood, irritability, nervousness, mood alterations

There is limited information regarding the use of Dienogest during pregnancy. Available animal studies and human data do not indicate significant risks to pregnancy or fetal development. However, Dienogest is generally not recommended during pregnancy because treatment of endometriosis is unnecessary at that time.

Use during lactation is also not recommended. Animal data suggest that Dienogest may pass into breast milk. A decision should be made whether to discontinue breastfeeding or stop therapy, considering the benefits to both the mother and child.

Pregnancy should be excluded before initiating Dienogest therapy. During treatment, patients are advised to use non-hormonal contraceptive methods such as barrier methods if contraception is needed.

As Dienogest is a progestogen-only preparation, precautions applicable to other progestogen therapies should also be considered:

• Changes in Bleeding Pattern: Menstrual bleeding patterns may change in many women during treatment
• Hepatic Impairment: Dienogest is contraindicated in patients with severe liver disease, whether current or past
• Impairment of Fertility: Ovulation may be suppressed during therapy; however, Dienogest is not a contraceptive. Non-hormonal contraceptive methods should be used if pregnancy prevention is desired

Use in Children: Dienogest is not indicated before menarche. Safety and efficacy in adolescents under 18 years have not been established.

Use in the Elderly: There is no relevant indication for Dienogest use in geriatric patients.

Acute toxicity studies have not shown a significant risk of serious adverse effects following accidental overdose. No specific antidote is available. Dienogest doses of 20–30 mg/day for over 24 weeks have generally been well tolerated.

Female Sex hormones

Store below 30°C, protected from light and moisture. Keep out of reach of children.