CLIMARA 25 25 MCG / 24 HOUR — DIN 02247499

What is CLIMARA 25?

CLIMARA 25 25 MCG / 24 HOUR contains ESTRADIOL (ESTRADIOL HEMIHYDRATE) : 25 MCG / 24 HOUR. It is listed in the Health Canada Drug Product Database under DIN 02247499, held by BAYER INC, supplied as PATCH for TRANSDERMAL administration. Health Canada currently lists it as marketed, status dated 30-Jul-2008. Nexara Health is a licensed Canadian wholesale distributor (DEL 3-002896-A) and can source this product for hospitals, pharmacies and clinics. Availability and lead time are confirmed per order.

What is CLIMARA 25 used for?

CLIMARA (estradiol hemihydrate transdermal system) is indicated for: • the relief of menopausal and postmenopausal symptoms occurring in naturally or surgically induced estrogen deficiency states. CLIMARA 50 and 75 are indicated for: • the prevention of osteoporosis in naturally occurring or surgically induced estrogen-deficiency states. In post-menopausal women already diagnosed as having osteoporosis and vertebral fractures, treatment with CLIMARA may retard further bone loss. CLIMARA 25 is not indicated for the prevention of osteoporosis. When CLIMARA is prescribed solely for the prevention of postmenopausal osteoporosis, it is to be considered in light of other available therapies. Adequate diet, calcium and vitamin D intake, cessation of smoking as well as regular physical weight bearing exercise are required in addition to the administration of CLIMARA. CLIMARA should be prescribed with an appropriate dosage of a progestin for women with intact uteri, in order to prevent endometrial hyperplasia/carcinoma.

Authorized indication as written in the Health Canada product monograph. For healthcare professionals and licensed purchasers; this is not medical advice.

How is it administered?

CLIMARA should be applied once a week and worn on a continuous basis for 7 days. It should be removed and a new one applied after 7 days. Only one patch should be worn at any one time during the 7-day dosing interval. Initiation of Therapy Three CLIMARA systems are available: CLIMARA 25 (0.025 mg/day), CLIMARA 50 (0.05 mg/day) and CLIMARA 75 (0.075 mg/day). Treatment is usually initiated with CLIMARA 50 applied to the skin once weekly. The dose should be adjusted as necessary to control symptoms. Clinical response at the lowest effective dose should be the guide for establishing administration of CLIMARA. The necessity for hormone replacement therapy for menopausal symptoms should be re-assessed periodically. Attempts to taper or discontinue the medication should be made at 3- to 6-month intervals. For the prevention of osteoporosis, CLIMARA 50 (0.05 mg/day) is the minimum dose approved. The choice of which dose to use should be made on the basis of individual considerations such as the age of the patient, other risk factors for osteoporosis and response to therapy as assessed by biochemical markers. Missed Dose If the patient forgets to apply the patch, then she should be counseled to apply a new patch and continue with her regular treatment schedule. Patch Application The physician should discuss the most appropriate placement of the patch with the patient. Immediately after removal of a patch from the pouch and removal of the protective liner, the adhesive side of the CLIMARA patch should be placed on a clean, dry area of intact skin. The area selected should not be oily, damaged or irritated, and not exposed to the sun. The site selected should also be one at which little wrinkling of the skin occurs during movement of the body, preferably the buttocks, lower abdomen or hip. The patch may also be placed on the side or lower back. The patch should be pressed firmly in place with the palm of the hand, making sure there is good contact, especially around the edges. In the event that a patch should fall off, a new one should be applied and the original treatment schedule should be continued. Patches should not be applied to the same skin site twice in succession. CLIMARA must not be applied to the breasts in order to avoid potentially harmful effects on the breast tissue.

Included because it drives pack selection and wastage. Consult the monograph.

Contraindications

CLIMARA (estradiol hemihydrate transdermal system) should not be used in individuals with any of the following conditions: • Hypersensitivity to this drug or to any ingredient in the formulation or component of the container. For a complete listing, see the Dosage Forms, Composition and Packaging section of the product monograph. • Liver dysfunction or disease as long as liver function tests have failed to return to normal. • Known or suspected estrogen-dependent malignant neoplasia (e.g. endometrial cancer). • Endometrial hyperplasia. • Known, suspected, or past history of breast cancer. • Undiagnosed abnormal genital bleeding. • Known or suspected pregnancy or lactation. • Active or past history of arterial thromboembolic disease (e.g. stroke, myocardial infarction, coronary heart disease). • Active or past history of confirmed venous thromboembolism (such as deep vein thrombosis or pulmonary embolism) or active thrombophlebitis. • A high risk of venous or arterial thrombosis, including known thrombophilic disorders (see WARNINGS AND PRECAUTIONS) • Partial or complete loss of vision due to ophthalmic vascular disease. • Presence or history of liver tumours (benign or malignant)

Warnings and precautions

Serious Warnings and Precautions The Women=s Health Initiative (WHI) trial examined the health benefits and risks of oral combined estrogen plus progestin therapy (n=16,608) and oral estrogen-alone therapy (n=10,739) in postmenopausal women aged 50 to 79 years. The estrogen plus progestin arm of the WHI trial (mean age 63.3 years) indicated an increased risk of myocardial infarction (MI), stroke, invasive breast cancer, pulmonary emboli and deep vein thrombosis in postmenopausal women receiving treatment with combined conjugated equine estrogens (CEE, 0.625 mg/day) and medroxyprogesterone acetate (MPA, 2.5 mg/day) for 5.2 years compared to those receiving placebo. The estrogen-alone arm of the WHI trial (mean age 63.6 years) indicated an increased risk of stroke and deep vein thrombosis in hysterectomized women treated with CEE-alone (0.625 mg/day) for 6.8 years compared to those receiving placebo. Other doses of oral conjugated estrogens with medroxyprogesterone acetate, and other combinations and dosage forms of estrogens and progestins were not studied in the WHI clinical trials and, in the absence of comparable data, these risks should be assumed to be similar. Therefore, the following should be given serious consideration at the time of prescribing: • Estrogens with or without progestins should not be prescribed for primary or secondary prevention of cardiovascular diseases. • Estrogens with or without progestins should be prescribed at the lowest effective dose for the approved indication. • Estrogens with or without progestins should be prescribed for the shortest period possible for the approved indication. • For the prevention of osteoporosis, Climara (estradiol hemihydrate transdermal system) should be considered in light of other available therapies. Breast Cancer: Available epidemiological data indicate that the use of combined estrogen plus progestin by postmenopausal women is associated with an increased risk of invasive breast cancer. In the estrogen plus progestin arm of the WHI trial, among 10,000 women over a one-year period, there were 8 more cases of invasive breast cancer (38 on combined HRT versus 30 on placebo). The WHI study also reported that the invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology but were larger and were at a more advanced stage compared with those diagnosed in the placebo group. In the estrogen-alone arm of the WHI trial, there was no statistically significant difference in the rate of invasive breast cancer in hysterectomized women treated with conjugated equine estrogens versus women treated with placebo. It is recommended that estrogens not be given to women with existing breast cancer or those with a previous history of the disease (see CONTRAINDICATIONS). Ovarian Cancer: Some recent epidemiologic studies have found that the use of hormone replacement therapy (estrogen-alone and estrogen plus progestin therapies), in particular for five or more years, has been associated with an increased risk of ovarian cancer. Endometrial Hyperplasia and Endometrial Carcinoma: Estrogen-only HRT increases the risk of endometrial hyperplasia if taken by women with intact uteri. Estrogen should be prescribed with an appropriate dosage of progestin for women with intact uteri in order to prevent endometrial hyperplasia/carcinoma. Pituitary Tumors: Close medical supervision (including periodic measurement of prolactin levels) is necessary if the patient suffers from hyperprolactinemia, prolactinoma, or is at risk of developing prolactinoma. Cardiovascular: The results of the Heart and Estrogen/progestin Replacement Studies (HERS and HERS II) and the Women's Health Initiative (WHI) trial indicate that the use of estrogen plus progestin is associated with an increased risk of coronary heart disease (CHD) in postmenopausal women. The results of the WHI trial indicate that the use of estrogen-alone and estrogen plus progestin is associated with an increased r