Testosterone Implant 100MG

Testosterone implant containing 100mg testosterone.

For a full list of excipients, see section 6.1

Implant for subcutaneous use.

Testosterone Implant 100MG is white to pale yellow, opaque or translucent and has a common cylindrical shape with a diameter of 4.5 mm and a length of 6 mm.

Testosterone replacement therapy in males for conditions associated with primary and secondary hypogonadism, either congenital or acquired.

Posology

100-600 mg depending on the individual requirements; in most hypogonadal men a dose of 600 mg maintains plasma testosterone levels within the normal male physiological range for 4-5 months.

Safety and efficacy have not been determined in children.

Method of implantation

Testosterone implants should be inserted subcutaneously into an area where there is relatively little movement or blood supply, such as the lower abdominal wall or the buttock. Insertion is made under local anaesthesia using a trocar and a cannula. The wound is closed either with an adhesive dressing or a fine suture. The implants must be placed subcutaneously to facilitate removal if necessary. In the rare event that removal of the implant should be necessary, the implant may be located by palpation. After localization, the implant can be removed after a small incision under local anesthetic.

Full aseptic "no touch" technique should be adopted.

In general, the dose should be adjusted according to the response of the individual patient.

Known or suspected carcinoma of the prostate or breast.

Hypersensitivity to the active substance or to any of the excipients.

Physicians should consider subjects receiving Testosterone Implant for monitoring before the start of treatment, at quarterly intervals for the first 12 months and yearly thereafter for the following parameters:

• Digital rectal examination (DRE) of the prostate and PSA to exclude benign prostate hyperplasia or a sub clinical prostate cancer,

• Hematocrit and hemoglobin to exclude polycythemia.

Physicians should also consider monitoring patients receiving Testosterone Implants, before implantation and at regular intervals thereafter, for testosterone, to confirm hypogonadism.

In patients with pre-existing cardiac, renal or hepatic disease, or hypertension androgen treatment may cause complications characterized by oedema with or without congestive heart failure.

Patients with epilepsy or migraine (or a history of these conditions) should be kept under close medical supervision, since aggravation of recurrence may occasionally be induced.

Androgens in general and Testosterone Implant can improve the glucose tolerance and the anticoagulant action (see also section 4.5).

Caution should be applied when treating men with sleep apnea. There have been reports that testosterone can cause or exacerbate pre-existing sleep apnea. However, there is a lack of evidence regarding the safety of testosterone in men with the condition. Good clinical judgment and caution should be employed in subjects with risk factors such as adiposity or chronic lung diseases.

In prepubertal children statural growth and sexual development should be monitored since androgens in general and Testosterone Implant in high dosages may accelerate epiphyseal closure and sexual maturation.

If androgen-associated adverse reactions occur treatment with Testosterone Implant should be discontinued with the patient and upon resolution of the complaints resumed with lower dosages.

Due to the long-lasting action and the difficulty of removal, Testosterone implants should be used with extra caution. Therefore, it may be advisable to establish the beneficial effect and tolerance for androgen therapy by prior treatment with a shorter-acting testosterone preparation. This applies in particular to (pre)pubertal boys and elderly men.

The use of steroids may influence the results of certain laboratory tests, (see Section 4.5).

Testosterone implants should be used with caution in cancer patients at risk of hypercalcaemia (and associated hypercalcuria), due to bone metastases. Regular monitoring of serum calcium concentrations is recommended in these patients.

Rarely benign and malignant liver tumours have been reported in patients receiving oral testosterone replacement therapy with 17 α–alkylated testosterone derivatives, however, this has not been observed with testosterone implants.

Androgens should not be used to enhance ability in sports as it carries serious health risks.

Enzyme-inducing drugs may decrease and enzyme-inhibiting drugs may increase plasma testosterone levels. Therefore, adjustment of the dose of Testosterone Implant may be required.

Testosterone and derivatives have been reported to increase the activity of oral anti-coagulants. High doses of androgens may enhance the anticoagulant action of coumarine type agents allowing a reduction of them dose of these agents. Patients receiving oral anti-coagulants require close monitoring, especially at the beginning or end of androgen therapy. Increased monitoring of the prothrombin time, and INR determinations, are recommended.

The concurrent administration of testosterone with ACTH or corticosteroids may enhance oedema formation; thus these active substances should be administered cautiously, particularly in patients with cardiac or hepatic disease or in patients predisposed to oedema.

Laboratory Test Interactions: Androgens may decrease levels of thyroxine binding globulin resulting in decreased total T4 serum levels and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.

Androgens may improve glucose tolerance and decrease the need for insulin or other anti-diabetic medicines (see section 4.4).

Testosterone Implant is not indicated for use in women. There are no adequate data for the use of Testosterone Implant in pregnant women. In view of the risk of virilization of the fetus, Testosterone Implant should not be used during pregnancy. Treatment with Testosterone Implant should be discontinued when pregnancy occurs. There are no adequate data for the use of Testosterone Implant during lactation. Therefore, Testosterone Implant should not be used during lactation.

As far as is known Testosterone implant has no effect on alertness and concentration.

Experience in the market has shown that the most frequent adverse events with Testosterone Implant are extrusion, infection and bruising or bleeding.

Due to the nature of Testosterone Implant, side effects cannot be quickly reversed by discontinuing medication.

The following adverse reactions have been associated with androgen therapy in general: Since the undesirable effects described below are derived from post marketing surveillance and based on general androgenic class labelling, the frequency could not be calculated.

Paediatric population

The following undesirable effects have been reported in prepubertal boys using androgens in general (see section 4.4): precocious sexual development, an increased frequency of erections, phallic enlargement and premature epiphyseal closure.

The acute toxicity of testosterone is low.

If symptoms of chronic overdose occur (e.g. polycythemia or priapism) the implant(s) should be removed and after disappearance of the symptoms, be resumed at a lower dosage.

Pharmacotherapeutic group: Androgens. ATC code G03B A03

Testosterone Implant inserted in every 4 to 5 months maintains plasma levels of testosterone and dihydrotestosterone in the normal physiological range of healthy males. In males with primary (hypergonadotropic) hypogonadism treatment with Testosterone Implant results in a normalization of gonadotropin levels. In hypogonadal men, treatment with Testosterone Implant results in an improvement of testosterone deficiency symptoms. Moreover, treatment increases bone mineral density and lean body mass, and decreases body fat mass. Treatment also improves sexual function, including libido and erectile function. Treatment increases hemoglobin and hematocrit, which may lead to polycytaemia. Testosterone also produces systemic effects, such as increasing the retention of sodium, potassium and chloride leading to an increase in water retention. Treatment may result in an increase in prostate size and PSA levels, and worsening of lower urinary tract symptoms. In boys with constitutional delay of growth and puberty, treatment with testosterone accelerates growth and induces development of secondary sex characteristics. In female-to-male transsexuals, treatment with testosterone induces masculinization.

Absorption:

Absorption of testosterone from 100 mg and 200 mg implants follows zero-order kinetics (constant rate absorption) throughout the effective life of the implants.

After insertion of 1200 mg (six 200 mg) testosterone implants, an initial short-lived burst release of testosterone with a peak-concentration of 50 nmol/L was revealed on day 1 with Tmax 12 h, which was followed by a stable testosterone concentrations around 35 nmol/L from day 2 to day 60. Thereafter testosterone serum concentrations declined gradually and were close to baseline concentrations at day 300. Mean testosterone serum concentrations were below 10 nmol/L after day 180.

The estimated rate of release of testosterone is 1.2 – 1.3 per day per 200 mg implant and 0.65 mg per day per 100 mg implant for the first three months. The release was nearly complete (95%) at 6 months after insertion.

Distribution:

Testosterone displays a high (over 97%) non-specific binding to plasma proteins and sex hormone binding globulin in in vitro tests.

Biotransformation:

Testosterone is metabolized to dihydrotestosterone and estradiol, which further are metabolized via the normal pathways.

Elimination:

Serum testosterone gradually declines to low normal testosterone levels after 4-10 months. The apparent terminal elimination half-life (t½) of Testosterone Implant is about 2.5 months. Once released from formulation testosterone has a short half life.Excretion mainly takes place via the urine as conjugates of etiocholanolone and androsterone.

Preclinical data with androgens in general reveal no hazards for humans.

None (Testosterone Implant consists of pure testosterone without any excipients).

Not applicable.

5 years.

Do not store above 25°C.

Store in the original package.

Each sterile implant is supplied singly in a sealed glass tube, positioned between plugs of non-absorbent wool.

Any unused product or waste material should be disposed of in accordance with local requirements.

See also "Special precautions for storage" and "Posology and method of administration".In correspondence please quote batch number.

Organon Laboratories Limited, Cambridge Science Park, Milton Road, Cambridge, CB4 0FL

PL 0065/5083R

04/10/2005

17 January 2011

Ref: UStest100v3.4

Testosterone Implant 100mg/01-11/1