Testosterone Combo 250 mg/ml

Testosterone Combo 250 mg/ml (Testosterone (as propionate, phenylpropionate, isocaproate and decanoate)) · ATC G03BA03

Androgen · multi-ester depot blend

Each 1 ml contains Testosterone Propionate 30 mg, Testosterone Phenylpropionate 60 mg, Testosterone Isocaproate 60 mg and Testosterone Decanoate 100 mg in a sterile oil carrier.

For the full list of excipients, see section 6.1.

Solution for injection in a single-use glass ampoule for deep intramuscular use.

Therapeutic indications

Androgen replacement therapy providing a sustained release profile from a single injection, as determined by a physician.

Posology and method of administration

Deep intramuscular injection as directed by a physician. Not for intravenous use. Rotate injection sites. Dose and interval are individualised by the prescriber.

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

Vitamin K antagonists (warfarin, acenocoumarol, phenprocoumon)

Androgens increase sensitivity to oral anticoagulants by depressing clotting factor synthesis; because this preparation gives prolonged androgen exposure, the anticoagulant effect may be enhanced for several weeks and INR must be monitored closely with dose adjustment by the prescriber.

Insulin and oral antidiabetic agents

Sustained androgen exposure improves insulin sensitivity and may lower blood glucose, so antidiabetic requirements may fall and hypoglycaemia can occur.

Corticosteroids and corticotrophin

Additive sodium and water retention with increased risk of oedema and hypertension, particularly relevant given the prolonged action of the ester blend.

5-alpha reductase inhibitors (finasteride, dutasteride)

Blockade of the conversion of testosterone to dihydrotestosterone reduces androgenic activity in prostate, skin and hair follicle without abolishing the systemic effects of testosterone; this pharmacodynamic interaction alters the balance of the response rather than serum testosterone concentrations.

CYP3A4 inducers and inhibitors

Enzyme inducers such as rifampicin, carbamazepine and phenytoin may accelerate oxidative metabolism of testosterone and reduce exposure, while potent inhibitors may increase it; the clinical relevance is greatest at the trough of the dosing interval.

Use in special populations

Pregnancy and breastfeeding

Contraindicated. The preparation may cause virilisation of a female foetus and the long-acting decanoate component means androgen exposure continues for weeks after the last dose, so pregnancy must be excluded and effective contraception used if a woman is exposed. Breastfeeding is contraindicated during treatment.

Paediatric population

Not recommended in children and adolescents; safety and efficacy have not been established. Androgen therapy before skeletal maturity accelerates bone age and risks premature epiphyseal closure with reduced final height, together with precocious virilisation; radiological bone-age monitoring is required if androgens are used in this setting.

Elderly

Data in men over 65 years are limited. Age-related prostatic disease, erythrocytosis, obstructive sleep apnoea and cardiovascular morbidity increase the risk profile; prostate evaluation including prostate-specific antigen, and haematocrit, should be assessed at baseline and periodically.

Renal impairment and cardiac failure

Caution is required because sodium and water retention may precipitate oedema, hypertension or cardiac decompensation; treatment should be discontinued if severe fluid retention occurs. No specific dose adjustment can be recommended.

Hepatic impairment

Contraindicated in severe hepatic insufficiency; in lesser impairment reduced clearance may prolong androgen exposure and hepatic function should be monitored during treatment.

Athletes

All four esters hydrolyse to testosterone and are prohibited at all times, in and out of competition, under class S1.1 of the WADA Prohibited List. The decanoate component in particular prolongs the window during which the steroid profile and carbon isotope ratio test will indicate exogenous testosterone administration. Athletes under anti-doping jurisdiction must not use this product without an approved therapeutic use exemption.

Undesirable effects

Endocrine

Dose-dependent suppression of LH and FSH with reduced endogenous testosterone production, testicular atrophy, oligospermia or azoospermia and impaired fertility, gynaecomastia related to aromatisation of the sustained testosterone load, virilisation in women

Blood and lymphatic system

Polycythaemia and increased haematocrit — a common finding with sustained-release testosterone preparations — increased blood viscosity and venous thromboembolism

Cardiovascular

Hypertension, oedema secondary to sodium retention, palpitations; myocardial hypertrophy and impaired ventricular function with prolonged supraphysiological exposure

Hepatobiliary

Elevated transaminases and gamma-glutamyl transferase, cholestasis and jaundice (uncommon with oil-based esters), peliosis hepatis and hepatic tumours after prolonged high-dose androgen use

Metabolism and investigations

Fall in HDL-cholesterol and rise in LDL-cholesterol, weight gain, altered glucose tolerance, suppressed sex hormone-binding globulin, increased prostate-specific antigen and haematocrit

Skin and subcutaneous tissue

Acne, seborrhoea, oily skin, increased body hair, androgenetic alopecia, urticaria

Psychiatric and nervous system

Altered libido, aggression, irritability, mood lability, nervousness, insomnia, headache; depression and lethargy after withdrawal

General and injection site

Injection-site pain and induration attributable chiefly to the propionate component, local inflammation, sterile abscess; rarely cough, dyspnoea and chest tightness immediately after injection consistent with pulmonary oil microembolism, and hypersensitivity to the arachis or other oily carrier

Overdose

Overdose is unlikely to be acutely life-threatening but, because the preparation contains a long-acting decanoate component, excessive androgen effects — erythrocytosis, hypertension, fluid retention, priapism, aggression and profound gonadotrophin suppression — may persist for several weeks after the last injection. There is no antidote; management consists of withholding further administration and providing symptomatic and supportive care, with monitoring of haematocrit, blood pressure, hepatic enzymes and lipids, and venesection where erythrocytosis is marked. Dialysis is ineffective because of high plasma protein binding.

Pharmacodynamic properties

Pharmacotherapeutic group: androgens, 3-oxoandrosten (4) derivatives; ATC code G03B A03. The product is a blend of four testosterone esters — propionate 30 mg, phenylpropionate 60 mg, isocaproate 60 mg and decanoate 100 mg per ml — all of which are prodrugs hydrolysed to the same active moiety, testosterone; the esters differ only in release rate, not in intrinsic pharmacology. Testosterone acts through the nuclear androgen receptor to maintain the male genital tract and secondary sexual characteristics, libido and potency, and to promote nitrogen retention, muscle protein synthesis, bone mineral density and erythropoiesis, with 5-alpha reduction to dihydrotestosterone and aromatisation to oestradiol modifying the response in individual target tissues. The purpose of the four-ester composition is a composite release curve in which the short esters provide rapid onset while the longer esters sustain concentrations, giving a smoother profile from a single injection than any single ester of comparable duration; suppression of hypothalamic and pituitary gonadotrophin secretion is nevertheless the same as for any testosterone preparation and is dose-dependent.

Pharmacokinetic properties

Each ester is released from the intramuscular oil depot at a rate determined by its side-chain lipophilicity and then hydrolysed by esterases: propionate is liberated fastest (apparent half-life approximately 0.8 days), followed by phenylpropionate (approximately 1.5 days) and isocaproate (approximately 2 days), with decanoate providing the long tail (approximately 5 days or more). The composite result is a rapid rise in serum testosterone to a maximum around 24 to 48 hours after injection, followed by a gradual decline towards baseline over approximately three weeks, so that no single terminal half-life describes the preparation. Released testosterone is approximately 98 % protein bound to sex hormone-binding globulin and albumin, and only the free and albumin-bound fractions are biologically available. Metabolism is hepatic — 5-alpha reduction, aromatisation via CYP19A1 and oxidation to 17-ketosteroids — and metabolites are conjugated and excreted mainly in urine, with a minor faecal component; on repeated administration at intervals set by the prescriber the long ester accumulates preferentially.

List of excipients

Refined oil carrier (vehicle for injection); benzyl benzoate 150 mg per 1 ml (co-solvent); benzyl alcohol 100 mg per 1 ml (co-solvent and antimicrobial preservative); butylated hydroxytoluene 0.2 mg per 1 ml (antioxidant); nitrogen (headspace overlay). The benzyl benzoate is required to hold four esters of differing chain length together at a combined 250 mg/ml without separation across the storage range; it also lowers the viscosity of the concentrate for intramuscular delivery.

Excipient warnings

This medicinal product contains 100 mg benzyl alcohol and 150 mg benzyl benzoate in each 1 ml ampoule. Benzyl alcohol may cause allergic reactions and, together with benzyl benzoate, may cause local irritation and pain at the injection site. Benzyl alcohol must not be administered to premature babies or neonates because of the risk of severe adverse reactions including "gasping syndrome". Patients who are pregnant or breastfeeding, and patients with hepatic or renal impairment, should be assessed by the prescriber, since large amounts of benzyl alcohol may accumulate and cause metabolic acidosis. The product also contains butylated hydroxytoluene, which may cause local skin reactions and irritation of the eyes and mucous membranes. As an oil solution it must not be given to patients with known hypersensitivity to the oil carrier.

Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. The concentrate must not be diluted, and must not be drawn into the same syringe as an aqueous injection or any other oil injection, as the co-solvent balance that keeps the four esters in solution would be disturbed.

Shelf life

36 months from the date of manufacture in the unopened container. Do not use after the expiry date stated on the ampoule and carton, which refers to the last day of that month.

After first opening

For single use only. Open immediately before administration, withdraw the whole 1 ml and inject without delay; discard any residual solution and never retain an opened ampoule. From a microbiological point of view, the product should be used immediately. This is a concentrated multi-ester solution: if it has been stored cool, or if any crystallisation or increase in viscosity is seen, warm the unopened ampoule to hand temperature and swirl gently until a single clear phase is obtained before use. Do not administer if the solution remains cloudy, separated or contains visible particles.

Storage

Store below 25 °C. Protect from light. Do not freeze. Keep ampoules in the outer carton until use.

Container

1 ml of solution in a 1 ml one-point-cut ampoule of Type I neutral borosilicate glass (Ph. Eur. 3.2.1 / USP <660>), amber or clear according to the presentation, flame-sealed under a nitrogen overlay to protect the concentrate from oxidation. Ten ampoules in a moulded tray within a serialised outer carton with the package leaflet; the carton carries a GS1 DataMatrix encoding GTIN, serial, lot and expiry, a human-readable serial and a scratch-off verification code. Pack size: 10 ampoules × 1 ml. Not all pack presentations may be marketed in every territory.

Disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements. Opened ampoules, residual oil solution, needles and syringes must be placed immediately into an approved sharps container for glass and needles; do not discard with domestic waste or into wastewater.

Pack

10 Ampoules × 1 ml

GTIN

05012345678908

Serial

3320 7741 0088 14

LOT

TC2608H

MFG

08 / 2026

EXP

08 / 2029

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.