Testosterone Cypionate 200 mg/ml

Testosterone Cypionate 200 mg/ml (Testosterone) · ATC G03BA03

Androgen · long-acting ester

Each 1 ml contains Testosterone Cypionate 200 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 in conditions associated with a deficiency of endogenous testosterone, 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

Coumarin anticoagulants (warfarin, acenocoumarol)

Androgens reduce the hepatic synthesis of clotting factors and displace anticoagulant from protein binding, potentiating the anticoagulant effect; INR may rise with an increased risk of bleeding and requires close monitoring when androgen therapy is started, changed or stopped.

Insulin and oral antidiabetic agents

Androgens improve insulin sensitivity and glucose tolerance, which may lower blood glucose and require adjustment of antidiabetic therapy by the prescriber to avoid hypoglycaemia.

Corticosteroids and corticotrophin

Additive sodium and water retention, with an increased likelihood of oedema; caution is required in patients with cardiac, hepatic or renal disease.

CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, barbiturates, St John's wort)

Increased oxidative metabolism of testosterone may reduce circulating androgen concentrations and attenuate the therapeutic effect; conversely strong CYP3A4 inhibitors may raise exposure.

Hepatotoxic medicinal products

Concomitant use with agents carrying a hepatotoxic potential may increase the likelihood of hepatic enzyme elevation and cholestatic injury; liver function should be monitored.

Use in special populations

Pregnancy and breastfeeding

Contraindicated. Androgens cross the placenta and may cause virilisation of a female foetus; there is no indication for use during pregnancy. Testosterone and its metabolites are excreted in breast milk and administration suppresses lactation, so use during breastfeeding is contraindicated. Women of childbearing potential should use effective contraception if exposure is unavoidable.

Paediatric population

Not indicated in children and adolescents; safety and efficacy have not been established. Androgen exposure before completion of growth accelerates skeletal maturation and may cause premature epiphyseal closure with reduced final height, as well as precocious virilisation. Where a prescriber uses androgens in delayed puberty, bone age should be monitored radiologically.

Elderly

Experience in patients over 65 years is limited and no specific dose recommendation can be made. Elderly men are at greater risk of benign prostatic hyperplasia, occult prostate carcinoma, erythrocytosis and cardiovascular events; digital rectal examination, prostate-specific antigen and haematocrit should be assessed before and during treatment as directed by the prescriber.

Renal impairment

No formal pharmacokinetic studies have been performed. Sodium and water retention may precipitate or aggravate oedema and hypertension, and caution is required in patients with impaired renal function or with cardiac failure; treatment should be discontinued if severe fluid retention occurs.

Hepatic impairment

Contraindicated in severe hepatic insufficiency. Testosterone is cleared predominantly by the liver, so exposure may be increased and the risk of cholestasis and enzyme elevation greater in hepatic impairment; periodic liver function testing is advised.

Athletes

Testosterone and its esters are classified as exogenous anabolic androgenic steroids under class S1.1 of the WADA Prohibited List and are prohibited in sport at all times, both in and out of competition. Use will produce an adverse analytical finding, and the long-acting cypionate ester remains detectable for an extended period after the last administration. Athletes subject to anti-doping regulation must not be treated with this product other than under a granted therapeutic use exemption.

Undesirable effects

Endocrine

Suppression of endogenous testosterone production and of LH and FSH, testicular atrophy, oligospermia or azoospermia with reduced fertility, gynaecomastia secondary to aromatisation, virilisation if administered to women (hirsutism, deepening of the voice, clitoromegaly, menstrual irregularity), some of which may be irreversible

Blood and lymphatic system

Erythrocytosis with rise in haemoglobin and haematocrit, increased blood viscosity, increased risk of venous thromboembolic events

Cardiovascular

Hypertension, peripheral oedema secondary to sodium and water retention, palpitations; with prolonged supratherapeutic exposure left ventricular hypertrophy and impaired diastolic function

Metabolism and nutrition, and investigations

Reduction in HDL-cholesterol and increase in LDL-cholesterol, weight gain, altered glucose tolerance, increased prostate-specific antigen, increased haematocrit, elevated hepatic transaminases

Hepatobiliary

Transient elevation of transaminases; rarely cholestasis and jaundice; with prolonged high-dose androgen exposure peliosis hepatis and hepatic tumours have been reported

Skin and subcutaneous tissue

Acne, seborrhoea, oily skin, increased body hair, male-pattern alopecia, urticaria and pruritus

Psychiatric and nervous system

Increased libido, irritability, aggression, mood lability, anxiety, insomnia, headache; depressed mood and fatigue on withdrawal, dependence with prolonged non-medical use

General disorders and injection site

Injection-site pain, erythema, induration, sterile abscess; rarely oil-solution reactions including pulmonary oil microembolism (cough, dyspnoea, chest tightness immediately after injection) and hypersensitivity reactions

Overdose

Acute overdose with an intramuscular depot ester is unlikely to give rise to a life-threatening situation, but because the drug is released from a tissue depot the resulting androgenic effects — erythrocytosis, hypertension, oedema, priapism, mood disturbance and marked gonadotrophin suppression — may persist for several weeks after exposure ceases. There is no specific antidote; management is symptomatic and supportive, with withdrawal of further administration, monitoring of haematocrit, blood pressure, hepatic function and lipids, and venesection considered where erythrocytosis is marked. Haemodialysis is not expected to be of value because of extensive plasma protein binding.

Pharmacodynamic properties

Pharmacotherapeutic group: androgens, 3-oxoandrosten (4) derivatives; ATC code G03B A03. Testosterone cypionate is the cyclopentylpropionate ester of the endogenous androgen testosterone and acts as a depot prodrug: following hydrolysis by non-specific esterases the liberated testosterone binds the intracellular androgen receptor, and the ligand-receptor complex engages androgen response elements to modulate gene transcription in muscle, bone, marrow, skin and the reproductive tract. Testosterone maintains male secondary sexual characteristics and libido, supports spermatogenesis, promotes nitrogen retention and lean tissue accrual, and stimulates erythropoiesis through increased erythropoietin and suppression of hepcidin. Part of the effect is mediated by metabolites: 5-alpha reduction to dihydrotestosterone amplifies activity in prostate, skin and hair follicle, while aromatisation to oestradiol mediates effects on bone maturation, epiphyseal closure and lipid handling. Exogenous administration exerts negative feedback on hypothalamic gonadotrophin-releasing hormone and on pituitary LH and FSH, suppressing endogenous testicular steroidogenesis.

Pharmacokinetic properties

After deep intramuscular injection of the oil solution the ester forms an intramuscular depot from which it is released slowly, the long cyclopentylpropionate side chain conferring high lipophilicity and the slowest release of the commonly used short and medium esters other than decanoate. Serum testosterone rises to a supraphysiological peak within approximately 24 to 48 hours and then declines over two to three weeks; the apparent terminal half-life is release-rate limited and is of the order of 8 days, so that steady state is approached only after repeated administration at intervals determined by the prescriber. Circulating testosterone is approximately 98 % protein bound, principally to sex hormone-binding globulin and albumin, with about 2 % unbound and pharmacologically available. Metabolism is predominantly hepatic, via 5-alpha reductase to dihydrotestosterone, via aromatase (CYP19A1) to oestradiol and by oxidation and CYP3A4-mediated pathways to androstenedione and 17-ketosteroids; roughly 90 % of a dose is excreted in urine as glucuronide and sulphate conjugates and about 6 % in faeces.

List of excipients

Refined oil carrier (vehicle for injection); benzyl alcohol 20 mg per 1 ml (co-solvent and antimicrobial preservative); nitrogen (headspace overlay). No other excipients are added; the solution is filled at 200 mg/ml and requires no additional co-solvent.

Excipient warnings

This medicinal product contains 20 mg benzyl alcohol in each 1 ml ampoule. Benzyl alcohol may cause allergic reactions. Benzyl alcohol has been associated with the risk of severe adverse reactions, including respiratory failure ("gasping syndrome"), in neonates and infants, and must not be administered to premature babies or neonates. Patients who are pregnant or breastfeeding, or who have hepatic or renal impairment, should be assessed by the prescriber before use, since large amounts of benzyl alcohol may accumulate and cause metabolic acidosis. The product is an oil solution; it must not be given to patients with known hypersensitivity to the oil carrier, in whom severe injection-site reactions may occur.

Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. In particular, being an oil solution it must not be combined in the same syringe with aqueous injections.

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. The ampoule is opened immediately before administration and the contents are withdrawn and injected in one operation; any solution remaining in an opened ampoule must be discarded and never retained for a later dose. From a microbiological point of view, the product should be used immediately after opening. The solution should be inspected before use and administered only if it is clear and free from visible particles; a faint yellow tint is characteristic of the oil carrier.

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>), supplied either amber or clear according to the presentation, filled under a nitrogen overlay. Ampoules are held in a moulded tray within a serialised outer carton of 10 ampoules together 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. Ampoules are single-use: opened ampoules, residual solution, used syringes and needles must be placed in an approved sharps container for glass and needles immediately after administration and must not be discarded with domestic waste or into wastewater.

Pack

10 Ampoules × 1 ml

GTIN

05012345678909

Serial

8821 0035 4417 09

LOT

CY2609J

MFG

09 / 2026

EXP

09 / 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.