AdultsThe dose of Lutigest is 100 mg administered vaginally three times daily starting at oocyte retrieval. The administration of Lutigest should be continued for 30 days, if pregnancy has been confirmed.
Paediatric populationThere is no relevant use of Lutinus in the paediatric population.
ElderlyNo clinical data have been collected in patients over age 65.
Use in special populationsThere is no experience with use of Lutigest in patients with impaired liver or renal function.
Method of AdministrationLutigest is to be placed directly into the vagina by the applicator provided.
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.
|System Organ Class (SOC)
|Common (> 1/100 and < 1/10)
|Uncommon (> 1/1000 and < 1/100)
|Not known*** (cannot be estimated from the available data)
|Nervous system disorders
|Abdominal distension Abdominal pain Nausea
|Skin and subcutaneous tissue disorders
|Reproductive system and breast disorders
|Vulvovaginal disorders* Vaginal mycosis Breast disorders** Pruritus genital
|General disorders and administration site conditions
Reporting of suspected adverse reactionsReporting 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.
Mechanism of actionProgesterone is a naturally occurring steroid that is secreted by the ovary, placenta, and adrenal gland. In the presence of adequate estrogen, progesterone transforms a proliferative endometrium into a secretory endometrium. Progesterone is necessary to increase endometrial receptivity for implantation of an embryo. Once an embryo is implanted, progesterone acts to maintain the pregnancy.
Clinical efficacy and safetyOngoing pregnancy and live birth rates following 10-week luteal support with Lutigest 100 mg TID (N=390) in patients who had an embryo transfer in the Phase III clinical trial were 44% (95% CI 38.9; 48.9) and with 39.5% (95% CI 34.6; 44.5), respectively
AbsorptionProgesterone serum concentrations increased following the administration of the Lutigest vaginal tablets in 12 healthy premenopausal females. On day 1 of treatment, the mean Cmax 19.8 ± 2.9 ng/mL with a Tmax of 17.3 ± 3.0 hours after administration of Lutigest three times daily 8 hours apart.On multiple dosing, steady state concentrations were attained within approximately 1 day after initiation of treatment with Lutigest. Trough values of 10.9 ± 2.7 ng/mL were observed with an AUC0-24 of 436 ± 43 ng*hr/mL on Day 5.
DistributionProgesterone is approximately 96 % to 99 % bound to serum proteins, primarily to serum albumin and corticosteroid binding globulin.
BiotransformationProgesterone is metabolized primarily by the liver largely to pregnanediols and pregnanolones. Pregnanediols and pregnanolones are conjugated in the liver to glucuronide and sulfate metabolites. Progesterone metabolites that are excreted in the bile may be deconjugated and may be further metabolized in the gut via reduction, dehydroxylation, and epimerization.
EliminationProgesterone undergoes renal and biliary elimination.Following injection of labelled progesterone, 50-60% of the excretion of metabolites occurs via the kidney; approximately 10% occurs via the bile and faeces. Overall recovery of the labelled material accounts for 70% of an administered dose. Only a small portion of unchanged progesterone is excreted in the bile.