Intrinsa

Posology The recommended daily dose of testosterone is 300 micrograms. This is achieved by applying the patch twice weekly on a continuous basis. The patch should be replaced with a fresh patch every 3 to 4 days. Only one patch is to be worn at a time.

Concomitant estrogen treatment The appropriate use and restrictions associated with estrogen therapy should be considered before Intrinsa therapy is initiated and during routine re-evaluation of treatment. e. the lowest effective dose for the shortest possible duration).

1). Duration of treatment Intrinsa treatment response should be evaluated within 3-6 months of initiation, to determine if continued therapy is appropriate. Patients who do not experience a meaningful benefit should be re- evaluated and discontinuation of therapy be considered.

Medicinal product no longer authorised 3 Special populations Renal impairment No studies have been conducted in patients with renal insufficiency. Hepatic impairment No studies have been conducted in patients with hepatic impairment.

Elderly Intrinsa is recommended for use in surgically menopausal women up to the age of 60. Consistent with the prevalence of HSDD, there are limited data above the age of 60. Paediatric population There is no relevant use of Intrinsa in the paediatric population.

Method of administration The adhesive side of the patch should be applied to a clean, dry area of skin on the lower abdomen below the waist. A particular application site should be rotated with an interval of at least 7 days between applications.

Patches should not be applied to the breasts or other body regions. A skin site with minimal wrinkling and not covered by tight clothing is recommended. The site should not be oily, damaged, or irritated. To prevent interference with the adhesive properties of Intrinsa, no creams, lotions or powder should be applied to the skin where the patch is to be applied.

The patch should be applied immediately after opening the sachet and removing both parts of the protective release liner. The patch should be pressed firmly in place for about 10 seconds, making sure there is good contact with the skin, especially around the edges.

If an area of the patch lifts, pressure should be applied to that area. If the patch detaches prematurely, it may be reapplied. If the same patch cannot be reapplied, a new patch should be applied to another location. In either case, the original treatment regimen should be maintained.

4 %) was application site reactions. The majority of these adverse reactions consisted of mild erythema and itching and did not result in patient withdrawal. Hirsutism was also very commonly reported. Most reports concerned the chin and upper lip, were mild (≥ 90 %), and less than 1 % of all patients withdrew from the studies due to hirsutism.

Hirsutism was reversible in the majority of patients. Other androgenic reactions commonly reported were acne, voice deepening and alopecia. More than 90 % of these reports were considered mild. These reactions were reversible in the majority of patients.

Less than 1 % of patients withdrew from the studies because of any of these reactions. All other common adverse reactions resolved in the majority of patients. Tabulated list of adverse reactions During 6-month double blind exposure the following adverse reactions occurred in the treatment group (n=549) at a greater incidence than placebo (n=545) and were assessed by the investigators as possibly or probably related to Intrinsa treatment.

If an adverse reaction occurred at a higher frequency in the integrated phase III studies (Intrinsa patients n=1,498, placebo patients n=1,297), this frequency is reported in the table. Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), or very rare (< 1/10,000), not known (cannot be estimated from the available data).

MedDRA System organ class Very common Common Uncommon Infections and infestations Sinusitis Blood and lymphatic system disorders Abnormal clotting factor Immune system disorders Hypersensitivity Metabolism and nutrition disorders Increased appetite Psychiatric disorders Insomnia Agitation, anxiety Nervous system disorders Migraine Disturbance in attention, dysgeusia, impaired balance, hyperaesthesia, oral paraesthesia, transient ischemic attack Eye disorders Diplopia, eye redness Cardiac disorders Palpitations Respiratory, thoracic and mediastinal disorders Voice deepening Nasal congestion, throat tightnessMedicinal product no longer authorised 6 MedDRA System organ class Very common Common Uncommon Gastrointestinal disorders Abdominal pain Diarrhoea, dry mouth, nausea Skin and subcutaneous tissue disorders Hirsutism Acne, alopecia Eczema, increased sweating, rosacea Musculoskeletal and connective tissue disorders Arthritis Reproductive system and breast disorders Breast pain Breast cyst, clitoral engorgement, enlarged clitoris, genital pruritus, vaginal burning sensation General disorders and administration site conditions Application site reaction (erythema, itching) Anasarca, asthenia, chest tightness, chest discomfort Investigations Increased weight Abnormal blood fibrinogen, increased heart rate, increased alanine aminotransferase, increased aspartate aminotransferase, increased blood bilirubin, abnormal liver function test, increased blood triglycerides

g. acne, changes in hair growth or hair loss). Patients should be advised to self assess for androgenic undesirable effects. Signs of virilisation, such as voice deepening, hirsutism or clitoromegaly, may be irreversible and discontinuation of treatment should be considered.

8). Hypersensitivity Severe skin erythema, local oedema and blistering may occur due to hypersensitivity to the patch at the site of application. Use of the patch should be discontinued if this occurs. Long-term safety, including breast cancer The safety of Intrinsa has not been evaluated in double blind placebo controlled studies of longer than 1 year duration.

Medicinal product no longer authorised 4 Data in the literature regarding the influence of testosterone on the risk of breast cancer in women are limited, inconclusive and conflicting. The long-term effect of testosterone treatment on the breast is currently unknown, therefore patients should be carefully monitored with regard to breast cancer in accordance with currently accepted screening practises and individual patient needs.

Cardiovascular disease Patients with known cardiovascular disease have not been studied. Patients with cardiovascular risk factors, in particular hypertension, and patients with known cardiovascular disease should be carefully monitored, specifically regarding changes in blood pressure and weight.

Diabetic patients In diabetic patients the metabolic effects of testosterone may decrease blood glucose and therefore insulin requirements. Patients with diabetes mellitus have not been studied. Endometrial effects Little information is available on the effects of testosterone on the endometrium.

The limited data evaluating the effect of testosterone on the endometrium neither allow conclusions nor reassurances on the incidence of endometrial cancer. Oedema Oedema (with or without congestive heart failure) may be a serious complication from high doses of testosterone or other anabolic steroids in patients with pre-existing cardiac, renal, or hepatic disease.

Hypersensitivity to the active substance or to any of the excipients. Known, suspected or past history of cancer of the breast or known or suspected estrogen-dependent neoplasia, or any other condition consistent with the contraindications for the use of estrogen.