Fareston

Posology The recommended dose is 60 mg daily. Renal impairment No dose adjustment is needed in patients with renal insufficiency. 2). Paediatric population There is no relevant use of Fareston in the paediatric population. Method of administration Toremifene is administered orally.

Toremifene can be taken with or without food.

The most frequent adverse reactions are hot flushes, sweating, uterine bleeding, leukorrhea, fatigue, nausea, rash, itching, dizziness and depression. The reactions are usually mild and mostly due to the hormonal action of toremifene.

The frequencies of the adverse reactions are classified as follows:

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) Very rare (< 1/10 000), not known (cannot be estimated from the available data). 4). Toremifene treatment has been associated with changes in liver enzyme levels (increases of transaminases) and in very rare occasions with more severe liver function abnormalities (jaundice).

A few cases of hypercalcaemia have been reported in patients with bone metastases at the beginning of toremifene treatment. Endometrial hypertrophy may develop during the treatment due to the partial estrogenic effect of toremifene.

There is a risk of increased endometrial changes including hyperplasia, polyps and cancer. 4). 4). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Gynaecological examination should be performed before treatment administration, closely looking at pre-existing endometrial abnormality. Afterwards gynaecological examination should be repeated at least once a year. g. 8). Anemia, leukopenia and thrombocytopenia have been reported.

Red blood cell, leukocyte or platelet counts should be monitored when using Fareston. Cases of liver injury, including elevation of liver enzymes (> 10 times upper limit of normal), hepatitis and jaundice have been reported with toremifene.

Most of them occurred during the first months of treatment. The pattern of the liver damage was predominantly hepatocellular. 8). Fareston has been shown to prolong the QTc interval on the electrocardiogram in some patients in a dose-related manner.

3). A QT clinical study with a 5-arm parallel design (placebo, moxifloxacin 400 mg, toremifene 20 mg, 80 mg, and 300 mg) has been performed in 250 male patients to characterize the effects of toremifene on the QTc interval duration.

The results of this study show a clear positive effect of toremifene in the 80 mg group with mean prolongations of 21–26 ms. Regarding the 20 mg group, this effect is significant as well, according to ICH guidelines, with upper confidence interval of 10–12 ms.

These results strongly suggest an important dose-dependent effect. As women tend to have a longer baseline QTc interval compared with men, they may be more sensitive to QTc-prolonging medications. Elderly patients may also be more susceptible to drug-associated effects on the QT interval.

Fareston should be used with caution in patients with ongoing proarrhythmic conditions (especially elderly patients) such as acute myocardial ischaemia or QT prolongation as this may lead to an increased risk for ventricular arrhythmias (incl.

3). If signs or symptoms that may be associated with cardiac arrhythmia occur during treatment with Fareston, treatment should be stopped and an ECG should be performed. If the QTc interval is > 500 ms, Fareston should not be used. Patients with non-compensated cardiac insufficiency or severe angina pectoris should be closely monitored.

1 - both in preclinical investigations and in humans, changes in cardiac electrophysiology have been observed following exposure to toremifene, in the form of QT prolongation. For reasons of drug safety, toremifene is therefore contraindicated in patients with:  congenital or documented acquired QT prolongation 3  electrolyte disturbances, particularly in uncorrected hypokalaemia  clinically relevant bradycardia  clinically relevant heart failure with reduced left-ventricular ejection fraction  previous history of symptomatic arrhythmias.

5).