Testafeme 10 mg Cream.

TestaFeme is indicated for the treatment of hypoactive sexual desire dysfunction (HSDD) in postmenopausal women. Treatment with TestaFeme should only be initiated in women following failure of appropriate education and correction of modifiable biopsychosocial factors (which may include neuroendocrine imbalance, physical ill health or disease, interpersonal difficulties, psychological distress or specific cultural or religious beliefs), according to the International Society for the Study of Womenu2019s Sexual Health (ISSWSH) process of care (see Figure 1).

Posology
The recommended starting dose is 5 mg testosterone (0,5 ml) applied once daily, at approximately the same time each day, to either the upper outer thigh or buttock. If no improvement in symptoms is seen within 3 months and if the testosterone concentration is within the premenopausal reference range a dose increases up to 10 mg testosterone (1,0 ml) daily can be used with follow up clinical and biochemical monitoring. This dose should only rarely be exceeded (see Monitoring). Clinical trials have shown that there is a four to eight-week time lag between starting testosterone treatment and an improvement in sexual motivation. If there is no improvement in symptoms after 6 months of continuous therapy, treatment should be discontinued, and alternative options be considered. There are no safety data for the use of TestaFeme beyond two years. Treatment should not exceed two years.
Method of administration
The patient should be directed to measure the appropriate dose using the graduated applicator and immediately apply to clean dry skin on the upper outer thigh or buttock. The cream should be massaged evenly until absorption is complete (typically around 30 seconds). The patient should be instructed to wash their hands with soap and water after each application. To clean the applicator after use, rinse in hot water. Absorption may be more variable if applied to other areas of the body. The dose can be varied according to severity of symptoms and clinical response. Do not apply to the genitalia or perineum.

• TestaFeme is contraindicated in patients with known sensitivity to testosterone, tree nuts (almond oil) or any of the excipients listed in section 6.1.
• TestaFeme is contraindicated in females with known or suspected carcinoma of the breast, known or suspected androgen-dependent neoplasia, nephrotic syndrome, history of thromboembolism or hypercalcaemia.
• TestaFeme is contraindicated in pregnancy and lactation.
• TestaFeme is contraindicated in women with normal reproductive function because of the potential for virilisation of a female foetus unless adequate contraceptive measures are being utilised.

Testosterone supplementation in women must be monitored closely, especially at onset of treatment (see section 4.2). Female testosterone requirements are between ten and twenty times less than that of males. Normal ranges for testosterone may vary between laboratories and between different assay methods. Androgenic side-effects may occur if doses are too high, therefore individual assessment and monitoring needs to be implemented on a patient-by-patient basis. If unwanted androgenic side-effects are experienced treatment should be halted and recommenced after reduced serum testosterone levels have been established. Levels typically return to baseline 2-5 days after ceasing treatment. All patients with pre-existing cardiac, hepatic or renal diseases need to be monitored closely when undergoing androgen treatment. High level athletes need to be aware of the rules governing androgen use if prescribed TestaFeme cream.
Potential for transfer
It has been reported that high dose transdermal testosterone preparations used in men can be transferred to other persons by close skin to skin contact, resulting in increased testosterone serum levels and, with repeated contact, possibly adverse effects. While the recommended dose of testosterone in TestaFeme is low by comparison to male doses, close skin contact with the area of application by a partner or child should be avoided. Patients should be made aware of the consequences of making sustained long-term close physical contact with young children. Long-term continual exposure may result in passive absorption and may have adverse effects, including virilisation, in young children. The risk of transfer is substantially reduced by wearing clothes covering the application area. The majority of residual testosterone is removed from the skin surface by washing with soap and water prior to contact.
As a result, the following precautions are recommended:
For the patient:

• Wash hands thoroughly with soap and water after applying the cream.
• Cover the application area with clothing once the cream has dried.
• Wash before any situation in which skin-to-skin contact is foreseen.

• In the event of sustained contact with an application area which has not been washed or is not covered with clothing, wash the area of skin onto which testosterone may have been transferred as soon as possible, using soap and water.
• Report the development of signs of excessive androgen exposure such as acne or hair modification. The patient must be particularly careful to avoid potential transfer to pregnant women.

All oral oestrogens (oral contraceptives and oral HRT) will result in an increase in SHBG which will bind testosterone and reduce bioavailability. Patients using oral oestrogen should be changed to transdermal oestrogen before being considered for testosterone therapy. The concurrent use of tibolone or glucocorticoids with testosterone may result in elevated testosterone levels due to a decrease in SHBG. Changes in insulin sensitivity, glucose tolerance, glycaemic control, blood glucose and glycosylated haemoglobin have been reported with androgens. In diabetic patients, medication requirements may change. When androgens are used simultaneously with oral anti-coagulants, the anti-coagulant effects may be increased. More frequent monitoring of INR and prothrombin time is recommended in patients taking anticoagulants, especially at the initiation and termination of androgen therapy. The concurrent use of testosterone with adrenocorticotropic hormone (ACTH) or corticosteroids may result in increased fluid retention and should be monitored, particularly in patients with cardiac, renal or hepatic disease. Concurrent administration of testosterone and bupropion may result in a lowered seizure threshold. Concurrent administration with ciclosporin may result in increased ciclosporin toxicity and elevated ciclosporin blood levels.

Fertility
TestaFeme has not been evaluated for possible effects on human fertility. Studies in animals have shown that testosterone has the potential to disrupt ovulation and impair fertility in females.
Pregnancy
Testosterone is contraindicated in women who are or who anticipate becoming pregnant (see section 4.3). Pregnant women must avoid any contact with TestaFeme application sites. Studies with testosterone in pregnant animals indicate the potential for adverse effects on embryofoetal development, including on the reproductive tract and cardiovascular system. Exposure of a foetus to androgens may result in varying degrees of virilisation. In the event of contact, women are advised to wash with soap and water as soon as possible.
Lactation
Testosterone suppresses prolactin in lactating females and may cause adverse effects in the infant. TestaFeme must not be used in breast-feeding women (see section 4.3). Care should be taken by breastfeeding women to avoid any contact with TestaFeme. In the event of contact, wash with soap and water as soon as possible.

No studies on the effects on the ability to drive and use machines have been performed. Patients should ensure that they do not engage in activities involving driving and the use of machines until they are aware of the measure to which TestaFeme affects them.

The following adverse events have been reported in clinical trials in postmenopausal women, using transdermal testosterone preparations providing similar systemic exposure to testosterone as TestaFeme when used as directed in section 4.2. That is, when physiological testosterone concentrations for premenopausal women are approximated.
Table 1. Common adverse events reported in clinical trials
Adverse Events Testosterone N (%) Placebo N (%) Acne 122 (7,5) 83 (0,5) Increased hair growth 212 (8,6) 106 (6,1) Alopecia 55 (4,5) 55 (4,4) Voice change 48 (3,7) 44 (3,4) Headache, abdominal bloating, and constipation have been reported in association with TestaFeme. In women, the inhibitory action of androgens on the activity of the anterior pituitary may result in the suppression of ovarian activity and menstruation. Continued administration of large doses may produce symptoms of virilism, such as male-pattern hirsutism or baldness, deepening of the voice, atrophy of the breasts and endometrial tissue, oily skin, acne, hypertrophy of the clitoris and suppression of lactation.
Potential side effects from excessive testosterone doses may include:

• nausea, vomiting, jaundice or swelling of the ankles,
• increased body hair,
• increased acne,
• signs of virilisation,
• weight gain,
• persistent headaches,
• deepening of the voice,
• electrolyte disturbances,
• polycythemia.

No cases of overdose with TestaFeme have been reported in clinical trials. Treatment of overdose would consist of discontinuation of TestaFeme together with appropriate symptomatic and supportive care. Wash the skin with soap and water.