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HRT, especially oestrogen-progestogen combined treatment, increases the density of mammographic images which may adversely affect the radiological detection of breast cancer.

In an interaction study with healthy volunteers, co administration of clopidogrel (300 mg loading dose), a CYP2C8 inhibitor, increased repaglinide exposure (AUC0 - ∞) 5.1-fold and continued administration (75 mg daily dose) increased repaglinide exposure (AUC0 - ∞) 3.9-fold. A small, significant decrease in blood glucose values was observed. Since the safety profile of the co-treatment has not been established in these patients, the concomitant use of clopidogrel and repaglinide should be avoided. If concomitant use is necessary, careful monitoring of blood glucose and close clinical monitoring should be performed (see section 4.4).Trials of combination therapy with Neutral Protamine Hagedorn (NPH) insulin or thiazolidinediones have been performed. However, the benefit risk profile remains to be established when comparing to other combination therapies. The risk of coronary artery disease is slightly increased in users of combined oestrogen-progestogen HRT over the age of 60 (see Section 4.4). HRT is associated with a 1.3-3 fold risk of developing venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism. The occurrence of such an event is more likely in the first year of HRT than later (see Section 4.8).

Repaglinide should only be prescribed if poor blood glucose control and symptoms of diabetes persist despite adequate attempts at dieting, exercise and weight reduction. Blood pressure and pulse may increase following discontinuation of guanfacine. In post-marketing experience, hypertensive encephalopathy has been very rarely reported upon abrupt discontinuation of treatment (see section 4.8). To minimise the risk of an increase in blood pressure upon discontinuation, the total daily dose should be tapered in decrements of no more than 1 mg every 3 to 7 days (see section 4.2). Blood pressure and pulse should be monitored when reducing the dose or discontinuing treatment. HRT is associated with a 1.3-3-fold increased relative risk of developing venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism. The occurrence of such an event is more likely in the first year of using HT (see Section 4.4). Results of the WHI studies are presented: An up to 2-fold increased risk of having breast cancer diagnosed is reported in women taking combined oestrogen-progestogen therapy for more than 5 years.

A number of medicinal products are known to influence repaglinide metabolism. Possible interactions should therefore be taken into account by the physician: In debilitated or malnourished patients the initial and maintenance dosage should be conservative and careful dose titration is required to avoid hypoglycaemic reactions. Caregivers must be very careful when handling used needles to prevent needle injury and cross-infection. If you are blind or have poor eyesight and cannot read the dose counter on the pen, do not use this pen without help. Get help Results of the secondary endpoints were consistent with that of the primary endpoint. The percentages of subjects who met response criteria (≥30% reduction from baseline in ADHD-RS-IV Total Score and a CGI-I value of 1 or 2) was 64.3% for guanfacine, 55.4% for atomoxetine and 42.3% for placebo. Guanfacine also showed significant improvement in learning, school and family functioning as measured with the (WFIRS-P score).

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