Adult: Replacement therapy in patients with congenital or acquired cases when testosterone deficiency is confirmed by biochemical tests and clinical features: As testosterone undecanoate: 1,000 mg every 10-14 weeks; 1st inj interval may be reduced to a minimum of 6 weeks depending on serum testosterone levels and clinical symptoms. Alternatively, initial doses of 750 mg, followed by 750 mg given after 4 weeks, then 750 mg injected every 10 weeks thereafter have been used. As testosterone propionate: 50 mg 2-3 times weekly. As testosterone enantate: Initially, 250 mg every 2-3 weeks. Maintenance: 250 mg every 3-6 weeks according to individual needs. Alternatively, 50-400 mg every 2-4 weeks. As testosterone cypionate: 50-400 mg every 2-4 weeks. All doses are administered via slow deep IM inj over 2 minutes. Dosage adjustment may be required according to serum testosterone levels. Dosing information may vary among individual products and between countries (refer to detailed product guideline). Elderly: As testosterone propionate: Dosage reduction may be necessary.
Nasal Male hypogonadism
Adult: Replacement therapy in patients with congenital or acquired cases when testosterone deficiency is confirmed by biochemical tests and clinical features: As metered-dose pump nasal gel: Each actuation delivers 5.5 mg. Recommended dose: 11 mg (2 pump actuations; 1 actuation per nostril) tid for a total dose of 33 mg daily. Dosage adjustment or discontinuation may be required depending on individual serum testosterone level (refer to detailed product guideline).
Oral Male hypogonadism
Adult: Replacement therapy in patients with congenital or acquired cases when testosterone deficiency is confirmed by biochemical tests and clinical features: As testosterone undecanoate cap: Initially, 120-160 mg daily in 2 divided doses for 2-3 weeks, then may be adjusted to the usual maintenance dose of 40-120 mg daily according to individual response. Alternatively, initial doses of 237 mg bid, adjusted to 158-396 mg bid based on individual serum testosterone levels have been used. Doses may be taken once in the morning and once at night; if the number of cap taken daily is uneven, the greater dose must be taken in the morning. Dosing information may vary among individual products and between countries (refer to detailed product guideline).
Transdermal Male hypogonadism
Adult: Replacement therapy in patients with congenital or acquired cases when testosterone deficiency is confirmed by biochemical tests and clinical features: As 1% gel or metered-dose pump gel: Recommended dose: Initially, apply 50 mg (1 tube, 1 packet, or 4 pump actuations) once daily, adjusted based on the pre-dose morning serum testosterone level at approx 7-14 days after initial therapy. Max: 100 mg daily. As 1.62% metered-dose pump gel: Initially, apply 40.5 mg (2 pump actuations) once daily, adjusted in increments of 20.25 mg (1 pump actuation) according to the morning pre-dose serum testosterone level. Max: 81 mg daily. Apply the 1% and 1.62% gel on a clean, dry, intact skin of the shoulders or upper arms, preferably in the morning. As patch delivering 2 mg/24 hours or 4 mg/24 hours: Recommended dose: Initially, apply 1 patch daily (as one 4 mg daily patch; not two 2 mg daily patches) at night for 24 hours on a clean, dry area of the skin on the abdomen, back, upper arms, or thighs. Dose range: 2-6 mg daily. Dose adjustment or discontinuation may be required depending on individual serum testosterone level (refer to detailed product guideline).
Known or suspected carcinoma of the breast (in males) or prostate; current or history of liver tumours, hypercalcaemia or hypercalciuria; men with hypogonadal conditions which are not associated with genetic or structural etiologies (e.g. age-related hypogonadism). Serious cardiac, hepatic and renal disease (cypionate inj). Pregnancy and lactation.
Patient with CV disease, ischaemic heart disease, coronary artery disease, hypertension, thrombophilia or risk factors for venous thromboembolism (VTE); epilepsy, migraine, existing or at risk of sleep apnoea (e.g. obesity, chronic lung diseases), depression; diabetes mellitus, benign prostatic hyperplasia; cancer patients at risk of hypercalcaemia or hypercalciuria (e.g. hypernephroma, bronchial carcinoma, skeletal metastases). Avoid treatment in men with previous MI or stroke within the past 6 months. Not indicated for use in women. Nasal gel: Not recommended for use in patients with history of nasal disorders, nasal or sinus surgery, nasal fracture (within the previous 6 months or which caused a deviated anterior nasal septum), mucosal inflammatory disorders (e.g. Sjogren’s syndrome) and sinus disease. Renal and hepatic impairment. Elderly.
Significant: Hypercalcaemia, hypercalciuria; may increase risk of breast or prostate cancer; exacerbated benign prostatic hyperplasia, sleep apnoea; hepatic neoplasm, cholestatic hepatitis, jaundice (prolonged use); oedema with or without CHF, increased blood pressure which increases the risk of major CV events (e.g. MI, stroke), changes in serum lipid profile, VTE (e.g. pulmonary embolism, DVT, ocular thrombosis), polycythaemia, gynaecomastia, priapism, oligospermia, azoospermia; drug abuse resulting in CV and psychiatric events, drug dependence and withdrawal symptoms; depression, suicidal ideation; severe rhinitis (nasal gel); virilisation in secondarily exposed children (transdermal gel). Gastrointestinal disorders: Nausea, diarrhoea, abdominal pain or discomfort. General disorders and administration site conditions: Inj site reactions (e.g. pain, discomfort, pruritus, erythema, haematoma, irritation), fatigue, asthenia; transdermal gel and patch: application site reactions (e.g. rash, erythema, pruritus, vesicles). Immune system disorders: Hypersensitivity reactions. Investigations: Increased haematocrit, weight, RBC count, Hb, prostate-specific antigen (PSA), blood creatine phosphokinase, estradiol, testosterone; decreased serum LDL-C, HDL-C, triglycerides. Metabolism and nutrition disorders: Electrolyte changes; hypercholesterolaemia. Musculoskeletal and connective tissue disorders: Myalgia, arthralgia; back pain (patch). Nervous system disorders: Headache, migraine, tremor, dizziness. Psychiatric disorders: Mood altered, nervousness. Renal and urinary disorders: Urinary obstruction or retention, nocturia, dysuria. Reproductive system and breast disorders: Prostate or breast induration, prostatitis, testicular pain, increased or decreased libido. Respiratory, thoracic and mediastinal disorders: Cough, sinusitis; nasopharyngitis, rhinorrhoea, epistaxis, nasal discomfort and scabbing, bronchitis, upper respiratory tract infection (nasal gel). Skin and subcutaneous tissue disorders: Pruritus, acne. Vascular disorders: Hypertension, hot flush. Potentially Fatal: Benign and malignant liver tumours leading to intraabdominal haemorrhage (IM); pulmonary oil microembolism (POME) and anaphylaxis (IM esters particularly undecanoate inj); peliosis hepatis (prolonged use).
Patient Counseling Information
Transdermal gel: Do not wash the site or shower for at least 2-6 hours after application. Cover application site(s) with clothing after the gel has dried. Before any situation where direct skin-to-skin contact with another person is anticipated, wash or cover application site thoroughly (e.g. shower before sexual contact). Do not apply to genitals. Avoid fire, flame, or smoking until the gel has dried out. Patch: Avoid showering, swimming, or washing the site of administration for at least 3 hours after application. Do not apply on the scrotum.
Local guidelines for safety monitoring must be considered during therapy. Before starting treatment, ensure adequate blood pressure control and patient’s baseline CV risk. Monitor serum total testosterone level at baseline and regularly during treatment; PSA and prostate examination (in men aged >40 years), haematocrit, and Hb prior to therapy, quarterly for the 1st 12 months of treatment, then yearly thereafter; LFTs and lipid profile; blood pressure prior to therapy, 3-6 weeks after initiation or dose adjustments then periodically thereafter; urine and serum Ca; bone mineral density after 1-2 years of therapy (in hypogonadal men with osteoporosis or low trauma fracture). After each inj, observe patients for 30 minutes to check for the occurrence of POME reactions or anaphylaxis (undecanoate IM inj). Assess patients for CV events, new-onset or worsening hypertension, depression, anxiety, mood changes, or suicidal ideation or behaviour.
May decrease effect with enzyme inducers (e.g. rifampicin, barbiturates, carbamazepine, phenytoin, primidone, phenylbutazone, dichloralphenazone). May enhance the effect of coumarin-type anticoagulants (e.g. warfarin). May increase risk of oedema with corticosteroids or ACTH. May cause improved glucose tolerance; dose adjustment of insulins and other antidiabetic agents may be necessary. May decrease the total testosterone concentration with oxymetazoline (nasal gel).
Enhanced absorption with food (cap).
May interfere with anti-doping testing. May reduce the level of thyroxine-binding globulin leading to decreased total T4 serum levels and increased T3 and T4 resin uptake.
Description: Testosterone is the principal endogenous androgen responsible for promoting the normal growth and development of male sexual organs and maintaining secondary sex characteristics in androgen-deficient males. Duration: IM esters: 2-4 weeks (cypionate and enantate); 10 weeks (undecanoate). Transdermal gel: 24 hours. Pharmacokinetics: Absorption: Absorbed from the gastrointestinal tract and through the skin (approx 10%); slowly absorbed after IM inj. Food enhances absorption (cap). Time to peak plasma concentration: IM (undecanoate): 7 days (range: 4-42 days); Transdermal patch: 8 hours (range: 4-12 hours); Oral: Approx 4-5 hours. Distribution: Enters breast milk. Plasma protein binding: 98%, mainly to sex hormone-binding globulin (40%) and albumin. Metabolism: Metabolised mainly in the liver to form dihydrotestosterone (DHT) and estradiol (major active metabolites). Undergoes extensive first-pass metabolism (oral). Excretion: Via urine (90% as sulfuric and glucuronic acid conjugates and metabolites); faeces (approx 6% as unchanged drug). Elimination half-life: Approx 10-100 minutes; approx 8 days (cypionate).
Cap: Store between 15-30°C. Protect from light and moisture. Solution for IM inj/transdermal gel: Store between 20-25°C. Protect from light. Patch: Store between 20-25°C. Protect from excessive heat exposure. Nasal gel: Store between 15-30°C. Follow applicable procedures for receiving, handling, administration, and disposal. Storage conditions may vary among countries or individual products (refer to detailed product guideline).