Mesterolone 25 mg

Mesterolone 25 mg (Mesterolone) · ATC G03BB01

Androgen · oral DHT-derived, non-aromatising

Each film-coated tablet contains Mesterolone 25 mg.

For the full list of excipients, see section 6.1.

Tablet for oral administration.

Therapeutic indications

Androgen therapy with a non-aromatising oral agent, as determined by a physician.

Posology and method of administration

Take orally as directed by a physician. Swallow whole with water. Do not exceed the prescribed dose.

Contraindications

Known hypersensitivity to the active substance or excipients. Known or suspected carcinoma of the prostate or male breast. Not for use in women, in pregnancy or while breastfeeding. Use with caution in cardiac, renal or hepatic impairment.

Special warnings and precautions for use

Keep out of the reach and sight of children. Contains a substance prohibited in sport (WADA).

Interaction with other medicinal products

Coumarin anticoagulants

Androgens may enhance the anticoagulant response with prolonged prothrombin time and bleeding risk; INR should be monitored more closely when treatment is started or stopped.

Insulin and oral antidiabetic agents

Androgens can improve insulin sensitivity and lower blood glucose, so antidiabetic requirements may need reduction.

Corticosteroids and corticotrophin

Increased likelihood of oedema and of acne, particularly in patients with impaired cardiac or hepatic function.

Enzyme-inducing medicinal products (for example rifampicin, carbamazepine, phenytoin)

Induction of hepatic metabolism may reduce plasma androgen concentrations and diminish therapeutic effect.

5-alpha-reductase inhibitors (finasteride, dutasteride)

No attenuation of androgenic effect is expected, since mesterolone is already 5alpha-reduced and is not a substrate for the enzyme; the pharmacological antagonism relied upon with testosterone does not apply.

Use in special populations

Pregnancy and breastfeeding

Contraindicated. Mesterolone is a potent androgen that crosses the placenta and may virilise a female foetus; it is not indicated in women and must not be used during breastfeeding.

Paediatric population

Not recommended in children. If used in adolescents under specialist supervision, skeletal maturation must be monitored radiologically because androgens can cause premature epiphyseal closure and reduced final height.

Elderly

Benign prostatic hyperplasia and latent prostatic carcinoma are common in this group; prostate examination, prostate-specific antigen and urinary symptoms should be assessed before and during treatment, and treatment stopped if obstruction or malignancy is suspected.

Hepatic impairment

Unlike 17alpha-alkylated oral androgens, mesterolone is not associated with cholestatic hepatitis or peliosis hepatis, but it is hepatically metabolised and caution with periodic liver function testing remains appropriate in hepatic disease.

Renal impairment

Metabolites are cleared renally; caution is advised in significant renal impairment, and patients with a tendency to oedema, hypertension or cardiac failure should be monitored, although fluid retention is less prominent than with aromatisable androgens.

Athletes

Mesterolone is an exogenous anabolic androgenic steroid within class S1.1a of the WADA Prohibited List and is prohibited at all times, in and out of competition; its metabolites are readily identified in urine by gas chromatography-mass spectrometry.

Undesirable effects

Reproductive system and breast disorders

Frequent or persistent erections, increased libido, inhibition of spermatogenesis with oligospermia at higher exposure, prostatic enlargement and acceleration of pre-existing prostatic carcinoma

Endocrine disorders

Suppression of luteinising hormone and follicle-stimulating hormone with reduced endogenous testosterone production; virilisation in women, including hirsutism, voice deepening and clitoral hypertrophy

Skin and subcutaneous tissue disorders

Acne, seborrhoea, increased body hair, androgenetic alopecia

Psychiatric disorders

Mood changes, irritability, restlessness, sleep disturbance

Investigations

Modest reduction in HDL-cholesterol; increases in haemoglobin and haematocrit

Hepatobiliary disorders

Isolated reports of altered liver function tests; the marked cholestatic hepatotoxicity typical of 17alpha-alkylated androgens is not a feature of this compound

General disorders

Nausea, headache, weight change

Musculoskeletal and connective tissue disorders

Premature epiphyseal closure if given to patients with incomplete skeletal maturation

Overdose

Acute overdosage is expected to be of low toxicity and may cause nausea, headache, priapism and, on repeated excessive exposure, suppression of spermatogenesis and virilising effects in women. There is no specific antidote; management is withdrawal of the product together with symptomatic and supportive care.

Pharmacodynamic properties

Mesterolone (ATC G03BB01) is an orally active androgen, chemically 1alpha-methyl-5alpha-dihydrotestosterone. It is a pure androgen receptor agonist with a strong androgenic and comparatively weak anabolic profile. Because the A-ring is already 5alpha-reduced it cannot be aromatised, so it produces no oestrogenic effects and does not give rise to oestrogenic gynaecomastia or oestrogen-mediated fluid retention. Importantly, mesterolone is not 17alpha-alkylated: oral activity derives from the 1alpha-methyl group, and the compound therefore lacks the characteristic cholestatic hepatotoxicity of 17alpha-alkylated oral androgens and has a less unfavourable effect on serum lipids. It binds sex hormone binding globulin with high affinity and, at therapeutic exposure, exerts negative feedback on pituitary gonadotrophin secretion with consequent suppression of endogenous testosterone and spermatogenesis.

Pharmacokinetic properties

Mesterolone is well absorbed from the gastrointestinal tract; the 1alpha-methyl substituent retards hepatic inactivation sufficiently to permit oral use without 17alpha-alkylation. Plasma protein binding is extensive, with a high affinity for sex hormone binding globulin and albumin. Metabolism is hepatic, proceeding by reduction of the 3-keto group and oxidation at C-17 to 1alpha-methylandrosterone and related 17-oxo metabolites, which are conjugated as glucuronides and sulphates. Elimination is predominantly renal as conjugated metabolites, with a smaller biliary contribution; the reported terminal elimination half-life is of the order of 12 to 13 hours.

List of excipients

Tablet core: lactose monohydrate, maize starch, povidone K25, methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216), magnesium stearate. Film-coat: hypromellose 5 cP, macrogol 400, talc, titanium dioxide (E171). All excipients comply with the current Ph. Eur. or USP-NF monograph.

Excipient warnings

This medicine contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. This medicine contains methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate (E216), which may cause allergic reactions, possibly delayed.

Incompatibilities

Not applicable. The film-coated tablet should be swallowed whole; compatibility with vehicles for extemporaneous dispersion has not been studied.

Shelf life

36 months from the date of manufacture in the unopened blister. Do not use after the expiry date printed on the carton and blister foil.

After first opening

No in-use shelf life applies to the blister presentation. Tablets should remain in the intact blister until the moment of administration; a tablet pressed out of the blister should be taken immediately and not returned to the pack or stored loose.

Storage

Store below 25 °C in a dry place. Keep tablets in the outer carton until use.

Container

Push-through blister of PVC/PVdC film sealed to hard-tempered aluminium foil, 10 tablets per blister strip, with a tamper-evident carton seal. Pack size: 50 film-coated tablets (5 strips) per serialised carton with the patient information leaflet, GS1 DataMatrix, human-readable serial and verification code.

Disposal

No special requirements for destruction. Any unused medicinal product or waste material should be disposed of in accordance with local requirements. Tablets must not be disposed of via wastewater or with household waste; unused tablets, part-used blisters and empty packaging should be returned to the point of supply for controlled disposal.

Pack

50 Tablets

GTIN

05012345678920

Serial

3296 1074 8529 20

LOT

MS2706F

MFG

08 / 2027

EXP

08 / 2030

Every carton carries a GS1 DataMatrix and a verification code; a pack can be checked at ergopharm.net/verify.

Ergopharm Advanced Research Centre, Tandalja, Vadodara, Gujarat 390012, India. For Export Only.

Report a suspected adverse reaction or quality defect to pv@ergopharm.net.