Testosterone

Registered South African indications:

• Testosterone replacement therapy for male hypogonadism

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Known or suspected prostatic cancer or breast carcinoma

Cautions

• Renal impairment (particularly in severe impairment)
• Hepatic impairment (particularly in severe impairment)
• Elderly
• Porphyria
• Use in women
• Risk factors for prostatic cancer (clinical or familial factors)
• Cancer patients at risk of hypercalcemia (and associated hypercalciuria)
• Severe cardiac insufficiency
• Ischaemic heart disease
• Hypertension
• Thrombophilia
• Risk factors for venous thromboembolism (VTE)
• Epilepsy
• Migraine
• Risk factors for sleep apnoea
  - Obesity
  - Chronic respiratory disease
• Diabetes mellitus
• Bodily contact between individuals, including children and pregnant women
• Damaged skin
• High dose
• Prolonged use

Forms avail. in SA and covered in this monograph: gel

Testosterone replacement therapy for male hypogonadism 
- When testosterone deficiency has been confirmed by clinical features and biochemical tests

• Topical (gel): 50mg, dly, at the same time each day (preferably in the morning); Titrate by steps of 2.5g gel depending on clinical or laboratory response; Max: 10g/24hrs 

Steady-state plasma testosterone concentrations are reached approximately on the 2nd day of treatment by this medicine

In order to adjust the testosterone dose, serum testosterone concentrations must be measured in the morning before application from the 3rd day on after starting treatment (one week seems reasonable)

The dose may be reduced if the plasma testosterone concentrations are raised above the desired level. If the concentrations are low, the dosage may be increased, not exceeding 10g of gel per day

Not established for use in children below 18 years

Pregnancy

• Not indicated for use in women
• Testosterone gel is intended for use by men only. This medicine is not indicated in pregnant women. No clinical trials have been conducted with this treatment in women
• Pregnant women must avoid any contact with this medicine's application sites. This product may have adverse virilizing effects on the foetus. In the event of contact, wash with soap and water as soon as possible

Breastfeeding

• Not indicated for use in women
• Testosterone gel is not indicated in women who are breastfeeding

Fertility

• Spermatogenesis may be reversibly suppressed with testosterone gel

Renal Impairment

• Caution; no information available
  In severe renal insufficiency, treatment with testosterone may cause severe complications characterised by oedema with or without congestive cardiac failure. In such a case, treatment must be stopped immediately

Hepatic Impairment

• Caution; no information available
  In severe hepatic insufficiency, treatment with testosterone may cause severe complications characterised by oedema with or without congestive cardiac failure. In such a case, treatment must be stopped immediately

Elderly

• Caution; no dose adjustment recommended
  There is limited experience on the safety and efficacy of the use of this medicine in patients over 65 years of age. Currently, there is no consensus about age specific testosterone reference values. However, it should be taken into account that physiologically testosterone serum levels are lower with increasing age

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Prohibited - At all times
  The attention of athletes is drawn to the fact that testosterone may produce a positive reaction in anti-doping tests

Central Nervous System Disorders

• Mood disorders
• Dizziness
• Paraesthesia
• Amnesia
• Hyperaesthesia
• Headache
• Nervousness
• Irritability
• Depression
• Hostility

Cardiovascular Disorders

• Hypertension
• Thrombotic events
  - Deep vein thrombosis
  - Pulmonary embolism
  - Ocular thrombosis

Respiratory Disorders

• Sleep apnoea

Gastrointestinal Disorders

• Diarrhoea

Hepatobiliary Disorders

• Hepatic neoplasm
• Jaundice
• Abnormal hepatic function test

Genitourinary Disorders

• Gynaecomastia
• Mastodynia
• Prostatic disorders
  - Progression of benign prostatic hyperplasia
• Urinary obstructions 2
• Libido changes
• Increased frequency of erections
• Reversible interruption or reduction in spermatogenesis (therapy with high doses of testosterone preparations)
• Reduced size of the testicles (therapy with high doses of testosterone preparations)
• Prostate abnormalities (therapy with high doses of testosterone preparations)
• Priapism

Endocrine and Metabolic Disorders

• Weight gain
• Electrolyte changes (retention of sodium, chloride, potassium, calcium, inorganic phosphate and water)

Musculoskeletal Disorders

• Muscle cramps

Skin and Subcutaneous Tissue Disorders

• Alopecia
• Urticaria
• Acne
• Seborrhoea
• Balding
• Skin irritation
• Dry skin
• Erythema

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
• Increased haematocrit
• Increased red blood count
• Increased haemoglobin
• Prostate cancer
• Water retention
• Oedema
• Changes in laboratory tests
  - Polycythaemia
  - Lipids

• Oral anticoagulants
• Corticosteroids
• Adrenocorticotropic hormone
• Corticosteroids
• Antidiabetic agents

Other interactions

• Interference with thyroid hormone tests
  (See additional prescribing points)

• Digital rectal examination
• Serum PSA
• Testosterone level
• Blood pressure

Specific cases may require

• Urine and serum calcium levels
• Haemoglobin level
• Haematocrit level
• Hepatic function
• Lipid profile
• Glucose level
• HbA1c
• Prothrombin time (when coadministered with anticoagulants)
• International Normalised Ratio (INR) (when coadministered with anticoagulants)
• Bone mineral density

Additional observations

• Cardiovascular events

Method of administration

• For transdermal use only
• The application should be administered by the patient himself, onto clean, dry, healthy skin over both shoulders, or both arms or abdomen
• After opening the sachets, the total contents must be extracted from the sachet and applied immediately onto the skin. The gel has just to be simply spread on the skin gently as a thin layer. It is not necessary to rub it on the skin. Allow drying for at least 3-5 minutes before dressing. Wash hands with soap and water after applications
• Do not apply to the genital areas as the high alcohol content may cause local irritation

Precautions for use

• Testosterone gel should be used only if hypogonadism (hyper- and hypogonadotrophic) has been demonstrated and if other etiology, responsible for the symptoms, has been excluded before treatment is started
• Testosterone insufficiency should be clearly demonstrated by clinical features (regression of secondary sexual characteristics, change in body composition, asthenia, reduced libido, erectile dysfunction etc.) and confirmed by 2 separate blood testosterone measurements
• Currently, there is no consensus about age-specific testosterone reference values. However, it should be taken into account that physiologically testosterone serum levels are lower with increasing age
• Due to variability in laboratory values, all measures of testosterone should be carried out in the same laboratory
• This medicine should not be used by women, due to possibly virilizing effects

Potential testosterone transfer

• Testosterone gel can be transferred to other persons by close skin to skin contact, resulting in increased testosterone serum levels and possible adverse effects (e.g. growth of facial and/or body hair, deepening of the voice, irregularities of the menstrual cycle) in case of repeated contact (inadvertent androgenization)
• Patients should be informed about the risk of testosterone transfer, for instance during close bodily contact between individuals including children and about safety instructions (see below)

The following precautions are recommended:

• For the patient:
  - Wash hands with soap and water after applying the gel
  - Cover the application area with clothing once the gel has dried
  - Wash the application area before any situation in which close contact is foreseen
• For people not being treated with this medicine:
  - In the event of adventitious contact with this medicine, the person affected should wash the affected area with soap and water, immediately
  - Report the development of signs of excessive androgen exposure such as acne or hair modification
• Patients should wait at least 1hr before showering or bathing after applying this medicine
• Pregnant women must avoid any contact with this medicine's application sites. In case of pregnancy of the partner, the patient must reinforce his attention to the precautions for use

Risk of prostatic cancer

• Prior to testosterone initiation, all patients should undergo a detailed examination in order to exclude a risk of pre-existing prostatic cancer
• Careful and regular monitoring of the prostate gland and breast must be performed in accordance with recommended methods (digital rectal examination and estimation of serum PSA) in patients receiving testosterone therapy at least once yearly and twice yearly in elderly patients and at-risk patients (those with clinical or familial factors)

Interaction with laboratory tests

• Androgens may decrease levels of thyroxin binding globulin, resulting in decreased T serum concentrations and in increased resin uptake of T and T. Free thyroid hormone levels, however, remain unchanged and there is no clinical evidence of thyroid insufficiency

Diabetic medication

• Improved insulin sensitivity, glucose tolerance, glycaemic control, blood glucose and glycosylated haemoglobin levels have been reported with androgens. In diabetic patients, the dose of antidiabetic medications may need reduction

Endogenous androgens, principally testosterone, secreted by the testes and its major metabolite DHT, are responsible for the development of the external and internal genital organs and for maintaining the secondary sexual characteristics (stimulating hair growth, deepening of the voice, development of the libido); for a general effect on protein anabolism; for development of skeletal muscle and body fat distribution; for a reduction in urinary nitrogen, sodium, potassium, chloride, phosphate and water excretion. Testosterone does not produce testicular development, but it reduces the pituitary secretion of gonadotropins. The effects of testosterone in some target organs arise after peripheral conversion of testosterone to estradiol, which then binds to oestrogen receptors in the target cell nucleus e.g. the pituitary, fat, brain, bone and testicular Leydig cells.

Sachet 50mg/5g

• Androgel (Medi Challenge) originator