Each 5 g sachet contains testosterone 0.050 g.
Excipients/Inactive Ingredients: Carbomer 980, Isopropyl myristate, 96% Ethanol, Sodium hydroxide, Purified water.
Pharmacotherapeutic group: Androgens. ATC code: G03B A03.
Pharmacology: Pharmacodynamics: Endogenous androgens, principally testosterone, secreted by the testes and its major metabolite DHT (dihydrotestosterone), 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: it reduces the pituitary secretion of gonadotropins.
The effects of testosterone in some target organs arise after peripheral conversion of testosterone to oestradiol, which then binds to oestrogen receptors in the target cell nucleus e.g. the pituitary, fat, brain, bone and testicular Leydig cells.
Pharmacokinetics: The percutaneous absorption of testosterone ranges from approximately 9% to 14% of the applied dose.
Following percutaneous absorption, testosterone diffuses into the systemic circulation at relatively constant concentrations during the 24 hour cycle.
Serum testosterone concentrations increase from the first hour after an application, reaching steady-state from day two. Daily changes in testosterone concentrations are then of similar amplitude to those observed during the circadian rhythm of endogenous testosterone. The percutaneous route therefore avoids the blood distribution peaks produced by injections. It does not produce supra-physiological hepatic concentrations of the steroid in contrast to oral androgen therapy.
Administration of 5 g of ANDROGEL produces an average testosterone concentration increase of approximately 2.5 ng/mL (8.7 nmol/L) in plasma.
When treatment is stopped, testosterone concentrations start decreasing approximately 24 hours after the last dose. Concentrations return to baseline approximately 72 to 96 hours after the final dose.
The major active metabolites of testosterone are dihydrotestosterone and oestradiol.
Testosterone is excreted, mostly in urine, and in faeces as conjugated testosterone metabolites.
Toxicology: Preclinical safety data: Testosterone has been found to be non-mutagenic in vitro using the reverse mutation model (Ames test) or hamster ovary cells. A relationship between androgen treatment and certain cancers has been found in studies on laboratory animals. Experimental data in rats have shown increased incidences of prostate cancer after treatment with testosterone.
Sex hormones are known to facilitate the development of certain tumours induced by known carcinogenic agents. No correlation between these findings and the actual risk in human beings has been established.
Testosterone replacement therapy for male hypogonadism when testosterone deficiency has been confirmed by clinical signs and biochemical tests (see Precautions).
Adult and Elderly men: The recommended dose is 5 g of gel (i.e. 50 mg of testosterone) applied once daily at about the same time, preferably in the morning. The daily dose should be adjusted by the doctor depending on the clinical or laboratory response in individual patients, not exceeding 10 g of gel per day. The adjustment of posology should be achieved by 2.5 g of gel steps.
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 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 application.
Do not apply to the genital areas as the high alcohol content may cause local irritation.
Steady-state plasma testosterone concentrations are reached approximately on the 2nd day of treatment by ANDROGEL. 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 (and up to one week). 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 10 g of gel per day.
Children: ANDROGEL is not indicated for use in children and has not been evaluated clinically in males under 18 years of age.
Only one case of acute testosterone overdose following an injection has been reported in the literature. This was a case of cerebrovascular accident in a patient with a high plasma testosterone concentration of 114 ng/mL (395 nmol/L). It would be most unlikely that such plasma testosterone concentrations be achieved using the transdermal route.
In cases of known or suspected prostatic cancer or breast carcinoma, in cases of known hypersensitivity to testosterone or to any other constituent of the gel.
ANDROGEL should be used only if hypogonadism (hyper- and hypogonadotrophic) has been demonstrated and if other aetiology, responsible for the symptoms, has been excluded before treatment is started. Testosterone insufficiency should be clearly demonstrated by clinical signs (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.
ANDROGEL is not a treatment for male sterility or impotence.
Prior to testosterone initiation, all patients must mandatorily 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: prostate-specific antigen) 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).
Androgens may accelerate the progression of sub-clinical prostatic cancer and benign prostatic hyperplasia.
ANDROGEL should be used with caution in cancer patients at risk of hypercalcaemia (and associated hypercalciuria), due to bone metastases. Regular monitoring of serum calcium concentrations is recommended in these patients.
In patients suffering from cardiac, hepatic or renal insufficiency, treatment with ANDROGEL may cause severe complications characterised by oedema with or without congestive cardiac failure. In this case, treatment must be stopped immediately. In addition, diuretic therapy may be required. Patients who experienced myocardial infarction, cardiac-, hepatic or renal insufficiency, hypertension, should be monitored due to the risk of deterioration of or reoccurrence of disease. In such cases treatment must be stopped immediately.
ANDROGEL should be used with caution in patients with ischemic heart disease.
Testosterone may cause a rise in blood pressure and ANDROGEL should be used with caution in patients with hypertension.
Testosterone level should be monitored at baseline and at regular intervals during treatment. Clinicians should adjust the dosage individually to ensure maintenance of eugonadal testosterone levels.
Besides laboratory tests of the testosterone concentrations in patients on long-term androgen therapy, the following laboratory parameters should be checked periodically: haemoglobin, haematocrit (to detect polycythemia), liver function tests and lipid profile. ANDROGEL should be used with caution in patients with epilepsy and migraine as these conditions may be aggravated.
There are published reports of increased risk of sleep apnoea in hypogonadal subjects treated with testosterone esters, especially in those with risk factors such as obesity and chronic respiratory disease.
Improved insulin sensitivity may occur in patients treated with androgens who achieve normal testosterone plasma concentrations following therapy.
Certain clinical signs: irritability, nervousness, weight gain, prolonged or frequent erections may indicate excessive androgen exposure requiring dosage adjustment.
If the patient develops a severe application site reaction, treatment should be reviewed and discontinued if necessary.
The attention of athletes is drawn to the fact that this proprietary medicinal product contains an active substance (testosterone) which may produce a positive reaction in anti-doping tests.
ANDROGEL should not be used by women, due to the possibility of virilising effects.
Potential testosterone transfer: If no precaution is taken, 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 repeat contact (inadvertent androgenisation).
The physician should inform the patient carefully about the risk of testosterone transfer and about safety instructions (see as follows).
ANDROGEL should not be prescribed in patients with a major risk of non-compliance with safety instructions (e.g. severe alcoholism, drug abuse, severe psychiatric disorders).
This transfer is avoided by wearing clothes covering the application site or showering prior to contact. As a result, the following precautions are recommended: for the patient: wash hands with soap and water after applying the gel; cover the application site with clothing once the gel has dried; shower before any situation in which this type of contact is foreseen.
for people not being treated with ANDROGEL: in the event of contact with an application site which has not been washed or is not covered with clothing, wash the area of skin onto which testosterone may have been transferred as soon as possible, using soap and water; report the development of signs of excessive androgen exposure such as acne or hair modification.
According to in vitro absorption studies on testosterone conducted with ANDROGEL, it seems preferable for patients to observe at least 6 hours between gel application and bathing or showering. Occasional baths or showers taken between 1 and 6 hours after application of the gel should not significantly influence the treatment outcome.
To guarantee partner safety, the patient should be advised for example to observe a long interval between ANDROGEL application and sexual intercourse, to wear a cloth covering the application site during contact period or to shower before sexual intercourse. Furthermore, it is recommended to wear a cloth, covering the application site, during contact period with children, in order to avoid a contamination risk.
Pregnant women must avoid any contact with ANDROGEL application sites. In case of pregnancy of the partner, the patient must reinforce his attention to the precautions for use (see Use in Pregnancy & Lactation).
Effects on ability to drive and use machines: ANDROGEL has no influence on the ability to drive or use machines.
ANDROGEL is intended for use by men only.
ANDROGEL is not indicated in pregnant or breast feeding women. No clinical trials have been conducted with this treatment in women.
Pregnant women must avoid any contact with ANDROGEL application sites (see Precautions). This product may have adverse virilising effects on the fetus. In the event of contact, wash with soap and water as soon as possible.
The most frequently observed adverse drug reactions at the recommended dosage of 5 g of gel per day were skin reactions (10%): Reaction at the application site, erythema, acne, dry skin.
Adverse drug reactions reported in 1-<10% of patients treated with ANDROGEL in the controlled clinical trials are listed in the following table: (See table.)
Click on icon to see table/diagram/image
Gynecomastia, which may be persistent, is a common finding in patients treated for hypogonadism.
The other known adverse drug reactions of oral or injectable treatments containing testosterone are prostatic changes and progression of sub-clinical prostatic cancer, urinary obstruction, pruritus, arterial vasodilatation, nausea, cholestatic jaundice, changes in liver function tests, increased libido, depression, nervousness, myalgia and, during high-dose prolonged treatment, electrolyte changes (sodium, potassium, calcium, inorganic phosphate and water retention), oligospermia and priapism (frequent or prolonged erections), haematocrit increased, red blood cell count increased and haemoglobin increased.
Because of the alcohol contained in the product, frequent applications to the skin may cause irritation and dry skin.
Oral anticoagulants: Changes in anticoagulant activity (the increased effect of the oral anticoagulant by modification of coagulation factor hepatic synthesis and competitive inhibition of plasma protein-binding): Increased monitoring of the prothrombin time, and INR determinations, are recommended. Patients receiving oral anticoagulants require close monitoring especially when androgens are started or stopped.
Concomitant administration of testosterone and ACTH or corticosteroids may increase the risk of developing oedema. As a result, these medicinal products should be administered cautiously, particularly in patients suffering from cardiac, renal or hepatic disease.
Interaction with laboratory tests: Androgens may decrease levels of thyroxin-binding globulin, resulting in decreased T4 serum concentrations and in increased resin uptake of T3 and T4. Free thyroid hormone levels, however, remain unchanged and there is no clinical evidence of thyroid insufficiency.
Oxyphenbutazone: Concurrent administration of oxyphenbutazone and androgens may result in elevated serum levels of oxyphenbutazone.
In diabetic patients, the metabolic effect of androgens may decrease blood glucose and therefore, insulin requirements.
Instructions for use: Handling and disposal: No special requirements.
Incompatibilities: Not applicable.
Store below 25°C.
Shelf-Life: 36 months.
G03BA03 - testosterone ; Belongs to the class of 3-oxoandrosten (4) derivative androgens used in androgenic hormone preparations.
Androgel topical gel 50 mg
5 g x 30 × 1's