1. Name Of The Medicinal Product
Testosterone Implant 200MG
2. Qualitative And Quantitative Composition
Testosterone implant containing 200mg testosterone.
3. Pharmaceutical Form
Implant for subcutaneous use.
4. Clinical Particulars
4.1 Therapeutic Indications
In the male: testosterone replacement therapy in primary or secondary hypogonadal disorders, for example:
- after castration,
- eunuchoidism,
- hypopituitarism,
- endocrine impotence,
- male climacteric symptoms such as decreased libido and decreased mental and physical activity.
Moreover, testosterone therapy may be indicated in osteoporosis in the male due to androgen deficiency.
In the female as an adjunct to estrogen replacement therapy in postmenopausal women to alleviate symptoms, such as decreased libido and/or loss of energy.
4.2 Posology And Method Of Administration
Posology
- In males:
100-600 mg depending on individual requirements. A dosage of 600 mg (6 x 100 mg) usually maintains plasma testosterone levels within the normal physiological range for 4-5 months.
- In females:
50-100 mg as an adjunct to Estradiol implants.
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. Full aseptic "no touch" technique should be adopted.
4.3 Contraindications
- Known or suspected prostatic carcinoma or breast carcinoma in the male
- Pregnancy
- Breast-feeding
4.4 Special Warnings And Precautions For Use
- Androgens should be used with caution in women to avoid unacceptable and irreversible virilization. Female patients should therefore be counselled to report any deepening or hoarsening of the voice without delay.
- Androgens should be used with caution in prepubertal boys to avoid premature epiphyseal closure or precocious sexual development. Skeletal maturation should be monitored regularly.
- 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, women and elderly men.
- Patients with latent or overt cardiac failure, renal or hepatic dysfunction, hypertension, epilepsy or migraine (or a history of these conditions) should be kept under close medical supervision, since aggravation of recurrence may occasionally be induced.
- If androgen-associated adverse reactions occur the implant should be removed if possible.
- The use of steroids may influence the results of certain laboratory tests, (see Section 4.5).
Physicians should consider monitoring patients receiving Testosterone Implants, before implantation and at regular intervals thereafter, for the following parameters:
- testosterone, to confirm hypogonadism
- digital rectal examination (DRE) of the prostate and PSA to exclude benign prostate hyperplasia or a sub-clinical prostate cancer. Androgens may accelerate the progression of subclinical prostatic cancer and benign prostatic hyperplasia.
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.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Enzyme-inducing drugs may influence plasma testosterone levels.
Testosterone and derivatives have been reported to increase the activity of oral anti-coagulants. 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.
Anti-diabetics: the hypoglycaemic effect is possibly enhanced due to improved insulin sensitivity.
4.6 Pregnancy And Lactation
Testosterone implants are contraindicated during pregnancy and lactation.
4.7 Effects On Ability To Drive And Use Machines
As far as known Testosterone implants have no effects on alertness and concentration.
4.8 Undesirable Effects
The following adverse reactions have been associated with androgen therapy:
- in general: water and sodium retention, hypercalcaemia;
- in women: symptoms of virilization, such as voice changes (deepening, hoarsening) and hirsutism;
- in prepubertal boys: precocious sexual development, increased frequency of erections, phallic enlargement and premature epiphyseal closure;
- in men: priapism and other signs of excessive sexual stimulation, oligospermia and decreased ejaculatory volume;
- extrusions occur in approximately 5% of the patients, depending upon the clinician's skill and experience. Most extrusions involve the loss of only a single implant and do not require specific treatment or replacement of implants;
- mild bleeding at the implantation site may occur occasionally within 2-3 hours after implantation and haematoma may occur within a few days after implantation;
- infection at the implantation site occurs rarely.
4.9 Overdose
The acute toxicity of testosterone is low. Priapism in men and undesired deepening of the voice in women are symptoms of chronic overdosage. In this case the implant(s) should be removed.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Testosterone is a naturally-occurring hormone formed in the interstitial cells of the testes under the control of the anterior lobe of the pituitary gland which controls the development and maintenance of the male sex organs and male secondary sex characteristics. Testosterone also produces systemic effects, such as increasing the retention of nitrogen, calcium, sodium, potassium, chloride and phosphate leading to an increase in skeletal weight, water retention and an increase in the growth of bone.
5.2 Pharmacokinetic Properties
Testosterone implants, when inserted subcutaneously release testosterone into the bloodstream at a relatively even rate supplying near physiological plasma testosterone levels.
Surface area of the implants is the most important factor influencing the rate of absorption. In general the absorption rate estimated by removal of implants at intervals and weighing appears to be appreciably more rapid than when the rate is assessed upon the clinical requirement. In addition to clinical evidence individual variation in the rate of absorption of implants must be taken into account.
The average daily absorption of testosterone has been estimated at 0.5mg for a 100mg implant with an approximate duration of 30 weeks.
5.3 Preclinical Safety Data
No particulars.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Testosterone implants are moulded pellets of pure testosterone (BP) without excipients.
6.2 Incompatibilities
No relevant incompatibilities are known.
6.3 Shelf Life
5 years.
6.4 Special Precautions For Storage
Do not store above 25°C.
Store in the original package.
6.5 Nature And Contents Of Container
Each sterile implant is supplied singly in a sealed glass tube, positioned between plugs of non-absorbent wool.
6.6 Special Precautions For Disposal And Other Handling
See "Posology and method of administration".
Administrative Data
7. Marketing Authorisation Holder
Organon Laboratories Limited, Cambridge SciencePark, Milton Road, Cambridge, CB4 0FL
8. Marketing Authorisation Number(S)
PL 0065/5084R
9. Date Of First Authorisation/Renewal Of The Authorisation
04/10/2005
10. Date Of Revision Of The Text
04/10/2005
Ref: UStest200v2.3
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