Endometrin 100

/ Ferring Pharmaceuticals

Adults: The dose of Endometrin is 100 mg administered vaginally three times daily starting at oocyte retrieval and continuing for up to 12 weeks total duration.
Paediatric population: There is no relevant use of Endometrin in the paediatric population.
Elderly: No clinical data have been collected in patients over age 65.
Use in special populations: There is no experience with use of Endometrin in patients with impaired liver or renal function.
Method of Administration: Endometrin is to be placed directly into the vagina by the applicator provided.

Progesterone supplementation or replacement in cases such as treatment of infertile women and IVF.

– Hypersensitivity to the active substance or to any of the excipients.
– Undiagnosed vaginal bleeding
– Known missed abortion or ectopic pregnancy
– Severe hepatic dysfunction or disease
– Known or suspected breast or genital tract cancer
– Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of these events
– Porphyria

Endometrin should be discontinued if any of the following conditions are suspected:
myocardial infarction, cerebrovascular disorders, arterial or venous thromboembolism (venous thromboembolism or pulmonary embolism), thrombophlebitis, or retinal thrombosis.
Cautious use in patients with mild to moderate hepatic dysfunction.
Patients with a history of depression need to be closely observed. Consider discontinuation if symptoms worsen.
Because progesterone may cause some degree of fluid retention, conditions that might be influenced by this factor (e.g. epilepsy, migraine, asthma, cardiac or renal dysfunction) require careful observation.
A decrease in insulin sensitivity and thereby in glucose tolerance has been observed in a small number of patients on oestrogen-progestogen combination drugs. The mechanism of this decrease is not known. For this reason, diabetic patients should be carefully observed while receiving progesterone therapy.
Sex steroid use may also increase the risk of retinal vascular lesions. To prevent these latter complications, caution is to be taken in users >35 years, in smokers, and in those with risk factors for atherosclerosis. Use should be terminated in case of transient ischemic events, appearance of sudden severe headaches, or vision impairments related to papillary edema or retinal hemorrhage.
Abrupt discontinuation of progesterone dosing may cause increased anxiety, moodiness, and increased sensibility to seizures.
Before starting treatment with Endometrin, the patient and her partner should be assessed by a doctor for causes of infertility.

The most frequently reported adverse drug reactions during treatment with Endometrin in IVF patients during clinical trials are headache, vulvovaginal disorders and uterine spasm, reported in 1.5%, 1.5% and 1.4% subjects, respectively.
See prescribing information for full details.

Drugs known to induce the hepatic cytochrome-P450-3A4 system (e.g. rifampicin, carbamazepine or St. John’s wort (Hypericum perforatum)-containing herbal products) may increase the elimination rate and
thereby decrease the bioavailability of progesterone.
In contrast ketoconazole and other inhibitors of cytochrome P450-3A4 may decrease elimination rate and thereby increase the bioavailability of progesterone.
The effect of concomitant vaginal products on the exposure of progesterone from Endometrin has not been assessed. However, Endometrin is not recommended for use with other vaginal products (such as antifungal products) as this may alter progesterone release and absorption from the vaginal tablet.

Pregnancy: Endometrin vaginal tablets are only indicated during the first trimester of pregnancy for use as part of an assisted reproduction (ART) regimen.
There is yet limited and inconclusive data on the risk of congenital anomalies, including genital abnormalities in male or female infants, following intrauterine exposure during pregnancy.
In the pivotal trial, the rate of foetal anomalies following 10-week exposure to Endometrin 100 mg TID was 4.5% in the Endometrin TID group, a total of 7 cases of foetal anomalies (i.e. oesophageal fistula, underdeveloped right ear with hypospadias, small aorta/ valvular regurgitation/ deviated septum, hand
deformity, cleft palate/cleft lip, hydrocephalus and holoprosencephaly/ proboscis/ polydactylia) were seen in 404 patients. The rate of foetal anomalies observed during the clinical trial is comparable with the event rate described in the general population, although the total exposure is too low to allow conclusions to be drawn.
During the conduct of the pivotal clinical trial, the number of spontaneous abortions and ectopic pregnancies associated with the use of Endometrin100 mg TID were 5.4% and 1%, respectively.
Breast-feeding: Detectable amounts of progesterone have been identified in the milk of mothers. Therefore Endometrin should not be used during lactation.

High doses of progesterone may cause drowsiness.
Treatment of overdosage consists of discontinuation of Endometrin together with institution of appropriate symptomatic and supportive care.

Shelf life: 5 years.
Storage: Store in a cool dry place (in a temperature not more than 25°C).