Testomax-phy-medic

PRESCRIBING INFORMATION
Testomax
NAME OF THE MEDICINAL PRODUCT
QUALITATIVE AND QUANTITATIVE COMPOSITION
Testomax 25 mg: Testosterone 0.025 g per 2.5 g sachet Testomax 50 mg: Testosterone 0.050 g per 5.0 g sachet For excipients, see List of excipients.
PHARMACEUTICAL FORM
CLINICAL PARTICULARS
Therapeutic indications
Testosterone replacement therapy for male hypogonadism when testosterone deficiencyhas been confirmed by clinical features and biochemical tests.
Posology and administration route
Adults and elderly
The recommended dose is 5 g of gel (i.e. 50 mg of testosterone) applied once daily, atabout the same time, preferably in the morning.
The daily dose should be adjusted by the doctor depending on the clinical or laboratoryresponse 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 administrated by the patient himself, onto clean, dry, healthyskin over the shoulders, arms and/or abdomen.
Once the sachet is open, the total content must be extracted from the sachet and appliedimmediately onto the skin. Let the gel dry for a few minutes before dressing. Wash handswith soap and water after application.
Steady state plasma testosterone concentrations are reached approximately on thesecond day of treatment with Testomax. In order to adjust testosterone dose, serum testosterone concentrations must be measured before application from the third day onafter starting treatment. The dose may be reduced if the plasma testosterone concentrationis high. If the concentration is low, the dosage may be increased, not exceeding 10 g ofgel per day.
Children
Testomax is not indicated for use in children and has not been evaluated clinically inmales less than 18 years old.
Contraindications
• in case of known or suspected breast carcinoma or prostatic cancer • in case of known hypersensitivity to testosterone or to any other constituents of the Testomax has not been evaluated in women and should not be used in women. Testomaxmay have adverse virilizing effects on the fetus in pregnant women (see Pregnancy andlactation).
Special warnings and special precautions for use
Human data
There are rare reports of hepatocellular carcinoma in patients receiving long-term oraltherapy with androgens in high doses. Withdrawal of the drugs did not lead to regressionof the tumors in all cases.
In patients suffering from severe cardiac, hepatic or renal insufficiency, treatment withTestomax may cause severe complications characterized by edema with or withoutcongestive cardiac failure. In this case, treatment must be stopped immediately.
Testomax should be used with caution in patients with ischemic heart disease.
Testosterone may cause a rise in blood pressure, and Testomax should be used withcaution in patients with hypertension.
Testomax should not be used if testosterone insufficiency has not been demonstratedand if other etiology, responsible for the symptoms, has not been excluded before treatmentis started. Testosterone insufficiency should be clearly demonstrated by clinical features(regression of secondary sexual characteristics, change in body composition, asthenia,reduced libido, erectile dysfunction, etc.) and confirmed by two separate blood testosteronemeasurements.
Testomax is not a treatment for male sterility or impotence.
Androgens may accelerate the progression of sub-clinical prostatic cancer and benignprostatic hyperplasia.
Testomax should be used with caution by patients suffering from cancer and having arisk of hypercalcemia (and associated hypercalciuria), due to bone metastases. Regularmonitoring of serum calcium concentrations is recommended in these patients.
Hematocrit determination should be checked periodically (to detect possible polycythemia)in patients on long-term androgen treatment.
Improved insulin sensitivity may occur in patients treated with androgens who achievenormal testosterone plasma concentrations following replacement therapy.
Testomax should be used with caution in patients with epilepsy and migraine, as theseconditions may be aggravated.
There are published reports of increased risk of sleep apnea in hypogonadal patientstreated with testosterone esters, especially in those with risk factors such as obesity andchronic respiratory disease.
Certain clinical signs such as: irritability, nervousness, weight increase, prolonged orfrequent erection may indicate excessive androgen exposure requiring a dosage adjustment.
The attention of athletes is drawn to the fact that this medicinal product contains an activesubstance (testosterone) which may produce a positive reaction in anti-doping tests.
Precautions for use
Prior to testosterone initiation, all patients, and especially elderly patients and at riskpatients (those with clinical or family factors), must undergo a detailed examination inorder to exclude any risk of pre-existing prostatic cancer.
Careful and regular monitoring of the prostate gland and breast must be performed inaccordance with recommended methods in patients receiving testosterone therapy.
A study performed with healthy volunteers has demonstrated that testosterone may betransferred to another person during close and relatively prolonged skin contact with thegel application area. This transfer was avoided by wearing clothes covering the applicationarea or showering prior to contact.
As a result, the following precautions are recommended: For the patient
• Wash hands with soap and water after application of the gel.
• Cover the application area with clothing once the gel is dried.
• Shower before any situation in which this type of contact is foreseen.
For people not being treated with Testomax
• In the event of contact with an application area which has not been washed or which has not been covered with clothing, wash the area of skin where testosterone mayhave been transferred as soon as possible, using soap and water.
• Report the development of signs of excessive androgen exposure such as acne or • Pregnant women must avoid any contact with Testomax application sites. In case of pregnancy of the partner, the patient must reinforce his attention to the precautionsfor use.
Laboratory tests
1. Hemoglobin and hematocrit levels should be checked periodically (to detect polycythemia) in patients on long-term androgen therapy.
2. Liver function, prostatic specific antigen, cholesterol, and high-density lipoprotein should 3. To ensure proper dosing, serum testosterone concentrations should be measured.
Interaction with other medicinal products and other forms of interaction
Association requiring precaution for use
Oral anticoagulantsChanges in anticoagulant activity (the increased effect of the oral anticoagulant bymodification of coagulation factors, hepatic synthesis and competitive inhibition ofplasma protein binding): increased monitoring of the prothrombin time and INRdeterminations are recommended. Oral anticoagulant dosage must be adjusted duringandrogen treatment and continued for 8 days after it is discontinued.
InsulinIn diabetic patients, the metabolic effects of androgens may decrease blood glucose and,therefore, insulin requirements.
PropranololIn a published pharmacokinetic study of an injectable testosterone product, administrationof testosterone cypionate led to an increased clearance of propranolol in the majority ofmen tested.
CorticosteroidsThe concurrent administration of testosterone with ACTH or corticosteroids may enhanceedema formation; thus, these drugs should be administered cautiously, particularly inpatients with cardiac, renal or hepatic disease.
Drug/laboratory interaction
Interaction with laboratory testAndrogens may decrease levels of thyroxine binding globulin, resulting in decreased T4serum concentrations and in increased resin uptake of T3 and T4. Free thyroid hormonelevels, however, remain unchanged and there is no clinical evidence of thyroid insufficiency.
Pregnancy and lactation
Testomax is contraindicated for pregnant or breastfeeding women. No clinical trials havebeen conducted with this treatment in women.
Pregnant women must avoid any contact with Testomax application areas. This productmay have adverse virilizing effects on the fetus. In the event of contact, wash with soapand water as soon as possible.
Effects on ability to drive and use machines
Testomax has no influence on the ability to drive or use machines.
Undesirable effects
The most frequently observed undesirable effects with the recommended dosage of5 g of gel per day were skin reactions (10%): reaction at the application area, erythema,acne, dry skin.
The other undesirable effects reported during clinical trials on Testomax were: headaches,alopecia, gynecomastia*, mastodynia, prostatic disorders, diarrhea, dizziness, asthenia,hypertension, mood disorders, changes in laboratory tests (polycythemia, etc.), reducedlibido, hyperesthesia, paresthesia.
The other known adverse effects of oral or injectable treatments containing testosterone Gynecomastia, which may be persistent, is a common finding in patients treated for hypogonadism.
are: prostatic changes and progression of sub-clinical prostatic cancer, pruritus, arterialvasodilatation, nausea, cholestatic jaundice, changes in liver function tests and, duringhigh-dose long-term treatment, electrolyte changes (sodium, potassium, calcium, inorganicphosphate) and water retention, oligospermia and priapism (frequent or prolongederection).
Because of the alcohol contained in the product, frequent application to the skin maycause irritation and dry skin.
Overdose
Only one case of acute testosterone overdose following an injection has been reportedin the literature. This was a case of a cerebrovascular accident in a patient with a highplasma testosterone concentration of 114 ng/ml (395 nmol/l). It would be most unlikelythat such plasma concentration be achieved using the transdermal route.
PHARMACOLOGICAL PROPERTIES
Pharmacodynamic properties
Endogenous androgens, principally testosterone, secreted by the testes and its majormetabolite DHT, are responsible for the development of the external and internal genitalorgans and for maintaining sexual characteristics (stimulating hair growth, deepening ofthe voice, development of the libido); for a general effect on protein anabolism; fordevelopment 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 secretionof gonadotropins.
Pharmacokinetic properties
The percutaneous absorption of testosterone ranges from about 7% to 13% of the applieddose.
Following absorption through the skin and saturation of the “cutaneous reservoir”,testosterone diffuses into the systemic circulation at relatively constant concentrationsduring the 24 hour cycle.
Serum testosterone concentrations increase from the first hour after an application,reaching a steady-state on the second day. Daily changes in testosterone concentrationsare then of similar amplitude to those observed during the circadian rhythm of endogenoustestosterone. The percutaneous route therefore avoids the blood distribution peaksproduced by injections. It does not produce supra-physiological hepatic concentrationsof the steroid in contrast to oral androgen therapy.
Administration of 5 g of Testomax produces an average testosterone concentrationincrease of approximately 2.5 ng/ml.
When treatment is stopped, testosterone concentrations start decreasing approximately24 hours after the last application. Concentration level returns to the baseline approximately72 to 96 hours after a new administration.
The major active metabolites of testosterone are dihydrotestosterone and estradiol.
Testomax is excreted mostly in urine and in feces as conjugated testosterone metabolites.
Preclinical safety data
Testosterone has been found to be non-mutagenic in vitro using the reverse mutationmodel (Ames test) or hamster ovary cells. A connection between androgen treatmentand certain cancers has been found in studies on laboratory animals.
Sex hormones are known to facilitate the development of certain tumors induced byknown carcinogenic agents. No correlation between these findings and the actual riskin human beings has been established.
PHARMACEUTICAL PARTICULARS
List of excipients
Carbomer 940, emersol 847, ethyl alcohol 200 proof, absolute, sodium hydroxide, purifiedwater.
Incompatibilities
Shelf-life
2 years
Special precautions for storage
Nature and contents of container
MANUFACTURER
Perrigo Israel Pharmaceuticals Ltd.
P.O.Box 16, YeruhamIsrael The format of this leaflet was determined by the Ministry of Health and its content was checked and approved by it in February 2007 Client:
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Status: Approved
Approval Date: 22.4.07
Approved by: Ety
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