LUTIGEST Vaginal tablet Ref.[7855] Active ingredients: Progesterone

Lutigest 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 Lutigest, the patient and her partner should be assessed by a doctor for causes of infertility.

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 Lutigest has not been assessed. However, Lutigest 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

Lutigest 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 Lutigest 100 mg TID was 4.5% in the Lutigest 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 Lutigest100 mg TID were 5.4% and 1%, respectively.

Breast-feeding

Detectable amounts of progesterone have been identified in the milk of mothers. Therefore Lutigest should not be used during lactation.

Lutigest has minor or moderate influence on the ability to drive and use machines. Progesterone may cause drowsiness and/or dizziness; therefore caution is advised in drivers and users of machines.

The most frequently reported adverse drug reactions during treatment with Lutigest in IVF patients during clinical trials are headache, vulvovaginal disorders and uterine spasm, reported in 1.5%, 1.5% and 1.4% subjects, respectively. The table below displays the main adverse drug reactions in women treated with Lutigest in the clinical trial distributed by system organ classes (SOCs) and frequency.

Common (> 1/100 and < 1/10)
Uncommon (> 1/1000 and < 1/100)
Not known*** (cannot be estimated from the available data)

Nervous system disorders

Common: Headache

Uncommon: Dizziness, Insomnia

Not known***: Fatigue

Gastrointestinal disorders

Common: Abdominal distension, Abdominal pain, Nausea

Uncommon: Diarrhoea, Constipation

Not known***: Vomiting

Skin and subcutaneous tissue disorders

Uncommon: Urticaria, Rash

Not known***: Hypersensitivity reactions

Reproductive system and breast disorders

Common: Uterine spasm

Uncommon: Vulvovaginal disorders*, Vaginal mycosis, Breast disorders**, Pruritus genital

General disorders and administration site conditions

Uncommon: Oedema peripheral

* Vulvovaginal disorders such as vulvovaginal discomfort, vaginal burning sensation, vaginal discharge, vulvovaginal dryness and vaginal haemorrhage, have been reported following use of Lutigest, with cumulative reporting frequency of 1.5%.
** Breast disorders, such as breast pain, breast swelling and breast tenderness have been reported in the clinical trial as single cases, with cumulative reporting frequency of 0.4%.
*** Cases seen during post marketing experience.

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 Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard.

Not applicable.