Duinum Special Precautions

Cases of hypertriglyceridemia have been reported (see Adverse Reactions) in the post-marketing experience with clomifene. Pre-existing or family history of hyperlipidemia and use of higher than recommended dose and/or longer duration of treatment with Duinum are associated with risk of hypertriglyceridemia. Periodic monitoring of plasma triglycerides may be indicated in these patients.
Multiple pregnancy: There is an increased chance of multiple pregnancy when conception occurs in relationship to clomifene therapy. The potential complications and hazards of multiple pregnancy should be discussed with the patient. During the clinical investigation studies, the incidence of multiple pregnancy was 7.9% (186 of 2369 clomifene associated pregnancies on which outcome was reported). Among these 2369 pregnancies, 165 (6.9%) twin, 11 (0.5%) triplet, 7 (0.3%) quadruplet and 3 (0.13%) quintuplet. Of the 165 twin pregnancies for which sufficient information was available, the ratio of monozygotic twins was 1:5.
Ectopic pregnancy: There is an increased chance of ectopic pregnancy (including tubal and ovarian sites) in women who conceive following clomifene therapy. Multiple pregnancies, including simultaneous intrauterine and extrauterine pregnancies, have been reported.
Uterine fibroids: Caution should be exercised when using Duinum in patients with uterine fibroids due to potential for further enlargement of the fibroids.
Pregnancy wastage and birth anomalies: The overall incidence of reported birth anomalies from pregnancies associated with maternal Duinum ingestion (before or after conception) during the investigational studies was within the range of that reported in the published references for the general population. Among the birth anomalies spontaneously reported in the published literature as individual cases, the proportion of neural tube defects has been high among pregnancies associated with ovulation induced by Duinum, but this has not been supported by data from population based studies.
The physician should explain so that the patient understands the assumed risk of any pregnancy whether the ovulation was induced with the aid of Duinum or occurred naturally.
The patient should be informed of the greater pregnancy risks associated with certain characteristics or conditions of any pregnant woman: e.g. age of female and male partner, history of spontaneous abortions, Rh genotype, abnormal menstrual history, infertility history (regardless of cause), organic heart disease, diabetes, exposure to infectious agents such as rubella, familial history of birth anomaly, and other risk factors that may be pertinent to the patient for whom Duinum is being considered. Based upon the evaluation of the patient, genetic counselling may be indicated.
Population based reports have been published on possible elevation of risk of Down's Syndrome in ovulation induction cases and of increase in trisomy defects among spontaneously aborted foetuses from subfertile women receiving ovulation inducing drugs (no women with Duinum alone and without additional inducing drug). However, as yet, the reported observations are too few to confirm or not confirm the presence of an increased risk that would justify amniocentesis other than for the usual indications because of age and family history.
The experience from patients of all diagnosis during clinical investigation of Duinum shows a pregnancy (single and multiple) wastage or foetal loss rate of 21.4% (abortion rate of 19.0%), ectopic pregnancies, 1.18%, hydatidiform mole, 0.17%, foetus papyraceous, 0.04% and of pregnancies with one or more stillbirths, 1.01%.
Duinum therapy after conception was reported for 158 of the 2369 delivered and reported pregnancies in the clinical investigations. Of these 158 pregnancies 8 infants (born of 7 pregnancies) were reported to have birth defects.
There was no difference in reported incidence of birth defects whether Duinum was given before the 19th day after conception or between the 20th and 35th day after conception. This incidence is within the anticipated range of general population.
Ovarian cancer: There have been rare reports of ovarian cancer with fertility drugs; infertility itself is a primary risk factor. Epidemiological data suggest that prolonged use of Duinum may increase this risk. Therefore the recommended duration of treatment should not be exceeded (see Dosage & Administration).
Effects on ability to drive and use machines: Patients should be warned that visual symptoms may render such activities as driving a car or operating machinery more hazardous than usual, particularly under conditions of variable lighting (see Precautions.)