Ретаболил

For use in osteoporosis in post-menopausal women

Established osteoporosis should have been diagnosed by the following parameters:

i) crush or wedge fractures of the vertebrae

ii) other osteoporotic fractures

iii) established reduction in bone mineral content as measured by accepted BMC measurements.

Posology:

Post-menopausal women

50mg every three weeks

The duration of treatment depends on the clinical response and the possible occurrence of side-effects.

We would recommend that the effectiveness of therapy be monitored with the appropriate methods for osteoporosis on a 6-12 monthly basis.

Method of administration:

Ретаболил should be administered by deep intramuscular injection

Pregnancy.

Breast-feeding

Porphyria

Hypersensitivity to the active substance or to any of the excipients, including arachis oil. Ретаболил is therefore contraindicated in patients allergic to peanuts or soya.

Medical examination:

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

- Hematocrit and hemoglobin to exclude polycythemia.

Conditions that need supervision:

Patients, especially the elderly, with the following conditions should be monitored for:

- Tumours - Mammary carcinoma, hypernephroma, bronchial carcinoma and skeletal metastases. In these patients hypercalcaemia or hypercalciuria may develop spontaneously, and also during androgen therapy. Nevertheless, the hypercalcaemia or hypercalciuria should first be treated appropriately and after restoration of normal calcium levels, if judged necessary and taking into account the risks and benefits on a case by case basis, hormone therapy can be resumed, with caution.

- Pre-existing conditions-In patients with pre-existing cardiac, renal or hepatic insufficiency/disease or epilepsy or migraine anabolic steroid treatment may cause complications characterized by oedema with or without congestive heart failure. In such cases treatment must be stopped immediately. Patients who experienced myocardial infarction, cardiac-, hepatic- or renal insufficiency, hypertension, epilepsy, or migraine should be monitored due to the risk of deterioration of or reoccurrence of disease. In such cases treatment must be stopped immediately.

- Diabetes mellitus - Ретаболил can improve glucose tolerance in diabetic patients.

- Anti-coagulant therapy - Ретаболил can enhance the anti-coagulant action of coumarin-type agents (see also section 4.5).

- Liver dysfunction - caution should be used in patients with severe hepatic impairment and Ретаболил 50mg/ml should only be used if the benefits outweigh the risks.

Adverse events:

If anabolic steroid-associated adverse reactions occur , treatment with Ретаболил should be discontinued and, upon resolution of complaints, treatment can be resumed.

Virilisation:

Patients should be informed about the potential occurrence of signs of virilisation. In particular, singers and women with speech professions should be informed about the risk of deepening of the voice.

If signs of virilisation develop, the risk/benefit ratio has to be newly assessed with the individual patient.

(Mis) use in sports:

Nandrolone is classified as a prohibited substance under the Olympic Movement Anti- doping Code (OMAC 1999). The misuse of Nandrolone and other anabolic steroids to enhance ability in sports carries serious health risks and is to be discouraged.

Excipients:

Ретаболил contains arachis oil (peanut oil) and should not be taken/applied by patients known to be allergic to peanut. As there is a possible relationship between allergy to peanut and allergy to soya, patients with soya allergy should also avoid Ретаболил.

Ретаболил 50mg/ml contains 100 mg benzyl alcohol per ml solution and must not be given to premature babies or neonates. Benzyl alcohol may cause anaphylactoid reactions in infants and children up to 3 years old.

Paediatric Population:

Safety and efficacy have not been adequately determined in children and adolescents. In pre-pubertal children statural growth and sexual development should be monitored since anabolic steroids in general and Ретаболил in high dosages may accelerate epiphyseal closure and sexual maturation.

Ретаболил has no influence on the ability to drive and use machines.

Due to the nature of Ретаболил, side effects cannot be quickly reversed by discontinuing medication. Injectables in general, may cause local reaction at the injection site.

Ретаболил at the recommended dosages is unlikely to produce virilising effects. High dosages, prolonged treatment and/or too frequent administration may cause:

* MedDRA version 15.0.

^1. Decrease in serum LDL-C, HDL-C and triglycerides.

Virilisation which appears in sensitive women as hoarseness, acne, hirsutism and increase of libido. Hoarseness may be the first symptom of vocal change which may end in long-lasting, sometimes irreversible deepening of the voice.

The terms used to describe the undesirable effects above are also meant to include synonyms and related terms.

The acute toxicity of nandrolone decanoate in animals is very low. There are no reports of acute overdosage with Ретаболил in the human.

Pharmacotherapeutic group: Anabolic steroids. ATC code: A14A B01

Nandrolone is chemically related to testosterone and shows enhanced anabolic and a reduced androgenic activity.

In humans Ретаболил has been shown to positively influence calcium metabolism and to increase bone mass in osteoporosis.

Androgenic effects (e.g. virilisation) are relatively uncommon at the recommended dosages. Nandrolone lacks the C17 alpha-alkyl group which is associated with the occurrence of liver dysfunction and cholestasis.

Absorption

Nandrolone decanoate is slowly released from the injection site into the blood with a half-life of 6 days.

Distribution

The ester is rapidly hydrolysed to nandrolone in the blood with a half-life of one hour or less. The half-life for the combined process of hydrolysis of nandrolone decanoate and of distribution and elimination of nandrolone is 4.3 hours.

Biotransformation and excretion

Nandrolone is metabolised by the liver. 19-norandrosterone, 19-noretiocholanolone and 19-norepiandrosterone have been identified as metabolites in the urine. It is not known whether these metabolites display a pharmacological action.

Toxicity studies in animals after repeated dosing did not indicate a safety risk for humans. No formal studies to assess reproduction toxicity, genotoxicity and carcinogenicity have been conducted by the company. As a class, anabolic steroids are considered to be probably carcinogenic to humans (IARC Group 2a).

The use of androgens in different species has resulted in virilisation of the external genitals of female foetuses. Investigations into the genotoxic potential of nandrolone showed it to be positive in an in vitro micronucleus assay and an in vivo micronucleus assay in mouse but not rat, and in the comet assay of mouse and rat. The clinical relevance of these findings is unknown, therefore the risk to patients cannot be ruled out.

None known

No special requirements for disposal.