Primoteston depot contains a derivative of the natural male sex hormone testosterone, testosterone enanthate as its active ingredient.
After intramuscular administration, testosterone enanthate becomes completely systemically available. The compound is gradually released from the depot with a half-life of about 4.5 days and is cleaved into testosterone and enanthic acid.
Maximum concentrations of testosterone of 20 ng/ml were measured 1.5 - 3 days after i.m. administration of 250 mg of testosterone enanthate to young men. Thereafter, testosterone levels in the plasma decreased with a half-life of about 4.5 days which corresponds to the release rate from depot.
Testosterone concentrations of=2 ng/ml were maintained for 20 days and concentrations=1 ng/ml for 26 days. With a dose of 250 mg testosterone enanthate, patients receive a total dose of 180 mg testosterone. Around the time where maximum serum levels are achieved, average daily doses after 1 and 2 weeks correspond to 12 and 4 mg testosterone, respectively. Within approximately 4 weeks after drug administration, testosterone is completely released from the depot.
Testosterone, which was generated by ester cleavage from testosterone enanthate, is metabolised and excreted the same way as endogenous testosterone. The enanthic acid is metabolised by ß-oxidation in the same way as other aliphatic carboxylic acids. The metabolic clearance of testosterone is calculated to be 16±7 ml/min/kg and refers to hepatic and extra-hepatic metabolism of testosterone. The metabolites of testosterone are eliminated with a half-life of 7.8 days. About 90 % are excreted renally and about 10 % with the bile.
Testosterone is highly bound to serum proteins, in particular to albumin and SHBG. The absolute bioavailability of testosterone from the ester was almost complete, indicating a rapid and efficient cleavage of the ester.
Injection of 250 mg testosterone enanthate every 3 - 4 weeks will not result in any clinically relevant accumulation of testosterone in serum.
Like all oily solutions, Primoteston depot must be injected intramuscularly. Experience shows that the short-lasting reactions (urge to cough, coughing fits, respiratory distress) which occur in rare cases during or immediately after the injection of oily solutions can be avoided by injecting the solution extremely slowly.
Disorders of potency based on an androgen deficiency are eliminated by administration of Primoteston depot. Mental changes, stress and conflict situations and physical ailments are frequently predominant in potency disorders. Supportive therapy with androgens can be beneficial during the elimination and treatment of causative factors and disorders.
For the therapy of diminishing androgen production - frequently with onset in middle age - and its possible concomitant symptoms, e.g. reduced performance, rapid fatigability, diminishing memory and ability to concentrate, disorders of libido and potency, depressive moods, irritability, sleep disturbances, general vegetative complaints.
The solvent of Primoteston depot has been used for many years in numerous formulations for human use. In this time no local irritant effects have been observed which could object to its further use. Many years of clinical experience have shown only sporadic cases in which allergenic reactions have been suspected. No clear sensitising effect has been proven.
On the whole, the available toxicological findings do not present any objections to the prescriptive use of Primoteston depot in humans for the given indications and at the dosages prescribed.
High-dosed or long -term administration of testosterone occasionally increases the tendency to water retention and oedema. Caution should therefore be exercised in patients predisposed to oedema.
In very rare cases jaundice and liver function test abnormalities were reported. Rare cases of polycythemia were reported. Gynaecomastia may occur in rare cases. Acne may occur.
Depending on the individual sensitivity to androgenic impulses, women may develop signs of virilisation, e.g. acne, hirsutism, voice changes (particular care is necessary in women whose occupations involve singing or speaking).
Phenobarbital increases the break down of steroid hormones in the liver (possible impairment of efficacy).
The clotting status should be monitored particularly closely when Primoteston depot is administered together with coumarin derivatives.