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Clinical surveillance of all women using estrogen-alone or estrogen plus progestin therapy is importantAdequate diagnostic measuresincluding directed or random endometrial sampling when indicatedshould be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

The effect of renal impairment on the pharmacokinetics of PREMARIN Vaginal Cream has not been studied.

Patients with a history of VTE or known thrombophilic states have an increased risk of VTEHRT may add to this riskHRT is therefore contraindicated in these patientssee section 4.3Personal or strong family history of thromboembolism or recurrent spontaneous abortion should be investigated in order to exclude a thrombophilic predisposition.

Estrogen therapy should be used with caution in women with hypoparathyroidism as estrogen-induced hypocalcemia may occur.

If VTE develops after initiating therapythe drug should be discontinuedPatients should be told to contact their doctors immediately when they are aware of potential thromboembolic symptomse.gpainful swelling of a legsudden pain in the chestdyspnoea

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