Neogest2 mg

Established Use

Neogest (2 mg oral tablet) is indicated for the treatment of endometriosis, specifically for the relief of endometriosis-associated pelvic pain. It is approved in many countries (including markets in Europe, Japan, Canada, and Bangladesh) as a stand-alone progestin therapy for this indication.

Combination-Therapy Use

Neogest is also used, in combination with an estrogen (estradiol valerate), as an active ingredient of certain combined oral contraceptive products. In that combined-hormone context it is used for pregnancy prevention and for management of heavy menstrual bleeding without organic cause; this monograph, however, describes Neogest used alone (monotherapy) for endometriosis.

Off-Label Use

Neogest monotherapy is sometimes used off-label, at the discretion of a gynecologist, for adenomyosis-related pain and for long-term suppression of endometriosis recurrence after surgery, although it is not formally approved for these indications in most labeling.

Each film-coated tablet contains Dienogest 2 mg as the active ingredient, along with pharmaceutically inert excipients such as lactose monohydrate, potato starch, povidone, magnesium stearate, hypromellose, and talc, which may vary by manufacturer.

Neogest is a synthetic progestogen (progestin) derived from 19-nortestosterone but pharmacologically distinct from older nortestosterone derivatives because it also carries pronounced anti-androgenic and anti-proliferative endometrial activity similar to natural progesterone. It is chemically designated as a 17α-cyanomethyl-19-nortestosterone derivative and is administered orally.

Marketed as a 2 mg once-daily tablet, Neogest is used clinically to reduce the growth of endometrial tissue and relieve the chronic pelvic pain associated with endometriosis.

Neogest belongs to the therapeutic class of progestins (progestogens), specifically a hybrid nortestosterone-derivative progestin with anti-androgenic and anti-endometriotic properties. It is classified under hormonal agents used in the management of endometriosis (ATC group: G03DB08).

Pharmacodynamics

Dienogest is a highly selective progesterone-receptor agonist with strong endometrial (progestogenic) activity, moderate anti-androgenic activity, and no significant estrogenic, androgenic, glucocorticoid, or mineralocorticoid activity. At the tissue level, Dienogest causes decidualization followed by atrophy of endometriotic tissue, reduces local production of prostaglandins and inflammatory mediators, and induces a hypoestrogenic, hypergestagenic hormonal milieu that suppresses the growth and activity of ectopic endometrial implants.

At the 2 mg/day dose used for endometriosis, Dienogest only partially and inconsistently suppresses ovarian estradiol production and ovulation; its clinical effect is achieved mainly through a direct, peripheral action on endometriotic tissue rather than strong central (pituitary-ovarian) suppression.

Pharmacokinetics

Dienogest is rapidly and almost completely absorbed after oral administration, with peak plasma concentration reached within about 1.5–4 hours and an absolute bioavailability of approximately 91%. It is metabolized predominantly via hepatic CYP3A4-mediated hydroxylation, and metabolites are excreted mainly in urine, with a terminal elimination half-life of approximately 9–10 hours.

Neogest is administered orally, once daily, at approximately the same time each day, with or without food, and swallowed whole with a glass of water. It is taken continuously (not cyclically), and treatment can be started on any day. See Dosage and Administration for missed-dose guidance.

Clinically Significant Interactions

• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir, certain macrolide antibiotics): may substantially increase plasma concentrations of Neogest, raising the risk of dose-related side effects.
• Strong CYP3A4 inducers (e.g., rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's Wort): may markedly decrease plasma concentrations of Neogest, reducing its therapeutic effect and increasing the likelihood of breakthrough bleeding.
• Hepatic enzyme-inducing anticonvulsants and antituberculosis drugs: share the same enzyme-induction mechanism as above and can reduce efficacy of Neogest.

Since Neogest at the endometriosis dose is not a reliable contraceptive, drug interactions that reduce hormonal contraceptive efficacy are less relevant to pregnancy prevention with this product; however, patients relying on hormonal contraception concurrently should discuss interacting medicines with their physician.

Very Common / Common

• Irregular uterine bleeding or spotting (very common, especially during the first months of use, sometimes progressing to amenorrhea with continued therapy)
• Headache
• Breast discomfort or tenderness
• Mood changes, including depressed mood or nervousness
• Acne
• Weight increase or weight fluctuation
• Decreased libido
• Abdominal pain, nausea
• Back pain

Less Common

• Hot flushes
• Vaginal dryness
• Hair loss (alopecia)
• Ovarian cysts
• Fatigue

Patients should report persistent, severe, or worsening symptoms — particularly signs suggestive of a blood clot (leg swelling/pain, chest pain, sudden breathlessness) or depression — to their physician promptly.

Pregnancy

Neogest is contraindicated in known or suspected pregnancy; it has no indication during pregnancy and epidemiological data on exposed pregnancies are limited. If pregnancy occurs or is suspected during treatment, Neogest should be discontinued immediately and a physician consulted.

Lactation

Small amounts of Neogest are excreted into breast milk. Because data on effects in nursing infants are limited, use of Neogest during breastfeeding is generally not recommended; a physician should weigh the mother's clinical need for treatment against potential infant exposure, and non-hormonal alternatives should be considered where feasible.

• Thromboembolic risk factors: Use with caution in women with risk factors for venous or arterial thromboembolism (e.g., obesity, smoking, immobilization, family history); discontinue and seek immediate care if symptoms of thrombosis develop (see Contraindications for absolute thrombotic contraindications).
• Mood changes: Neogest has been associated with new-onset or worsening depression; monitor mood, especially in patients with a history of depressive disorders, and discontinue if significant depressive symptoms occur.
• Hepatic impairment: Use with caution in mild hepatic impairment and avoid in patients with active or a history of severe liver disease (see Contraindications); monitor liver function if hepatic symptoms occur.
• Irregular bleeding: Uterine bleeding patterns commonly change during treatment; persistent or heavy bleeding should be evaluated by a physician to exclude other causes.
• Ovarian cysts: Functional ovarian cysts, including hemorrhagic cysts, may occasionally occur and usually resolve spontaneously.
• Not a reliable contraceptive: At the 2 mg/day endometriosis dose, Neogest does not consistently inhibit ovulation and must not be relied upon for contraception; a non-hormonal method (e.g., barrier method) should be used if pregnancy prevention is required, unless a specific combination product approved for contraception is being used instead.
• Bone mineral density: Prolonged hypoestrogenic effects with long-term use may theoretically affect bone density; discuss long-term use plans with a physician.

There is limited clinical experience with acute overdose of Neogest. Based on its pharmacological profile, an overdose is not expected to cause serious or life-threatening toxicity, though symptoms such as nausea, vomiting, or irregular vaginal bleeding could theoretically occur. There is no specific antidote. If an overdose of Neogest is suspected, seek immediate medical attention or contact a poison control center; treatment should be supportive and symptomatic, guided by a physician.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Pediatric Use

The safety and efficacy of Neogest have not been established in girls who have not yet menstruated (pre-menarche). In adolescents who have started menstruating, use should be individualized and supervised by a specialist, as clinical experience is more limited than in adult women.

Elderly / Postmenopausal Use

Neogest is not indicated for use in postmenopausal women, as endometriosis is a condition of the reproductive years; there is no relevant use of Neogest in this population.

Hepatic Impairment

Neogest is contraindicated in patients with severe hepatic disease or liver tumors, and should be used cautiously, with monitoring, in mild hepatic impairment (see Contraindications and Precautions).

Renal Impairment

Formal dose-adjustment studies in renal impairment are limited; Neogest should be used with caution and physician oversight in patients with significant renal impairment.

The duration of treatment with Neogest is determined by the prescribing physician based on symptom relief, tolerability, and treatment goals. Clinical trials supporting its use in endometriosis have evaluated continuous treatment for up to 15 months to 2 years, but many patients continue long-term therapy under medical supervision as long as benefit outweighs risk. Treatment should be reassessed periodically by a physician.

Dienogest is classified as a progestin (progestogen), specifically a nortestosterone-derivative progestin with anti-androgenic and anti-endometriotic activity, within the broader class of hormonal agents used to treat endometriosis.

Dienogest acts primarily as a selective agonist at the progesterone receptor. It produces decidualization and subsequent atrophy of both eutopic and ectopic (endometriotic) endometrial tissue, suppresses local prostaglandin and inflammatory mediator production, and creates a hypoestrogenic, hypergestagenic hormonal environment. Unlike combined hormonal contraceptives, Dienogest at the 2 mg/day endometriosis dose exerts its principal therapeutic effect through this direct, peripheral action on endometrial/endometriotic tissue rather than through consistent central suppression of ovulation.

The safety and efficacy of Neogest have not been formally established in children who have not begun menstruating. In postmenarchal adolescents with symptomatic endometriosis, Neogest may be used under close specialist supervision, but clinical trial experience in this age group is limited compared with adult women, so a conservative, individualized approach is recommended, with attention to growth, bone health, and mood monitoring.