Lutiges 100 mg Vaginal tablets.

LUTIGES u00ae is indicated for luteal support as part of an Assisted Reproductive Technology (ART) treatment programme for infertile women.

Posology

Adults

The dose of LUTIGES u00ae is 100 mg administered vaginally three times daily starting at oocyte retrieval. The administration of LUTIGES u00ae should be continued for 30 days, if pregnancy has been confirmed.

Paediatric population

There is no relevant use of LUTIGES u00ae in the paediatric population.

Elderly

No clinical data have been collected in patients aged over 65.

Use in special populations

There is no experience with use of LUTIGES u00ae in patients with impaired liver or renal function.

Method of administration

LUTIGES u00ae is to be placed directly into the vagina by the applicator provided.

LUTIGES u00ae should not be used in individuals with any of the following conditions:

• hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1
• undiagnosed vaginal bleeding
• known missed abortion or ectopic pregnancy
• severe hepatic dysfunction (child-pugh class C) 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.

LUTIGES u00ae 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 LUTIGES u00ae 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 medicines. The mechanism of this decrease is not known. For this reason, diabetic patients should be carefully observed while receiving LUTIGES u00ae therapy.

LUTIGES u00ae 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 oedema or retinal haemorrhage.

Abrupt discontinuation of progesterone dosing may cause increased anxiety, moodiness, and increased sensibility to seizures.

Before starting treatment with LUTIGES u00ae, the patient and her partner should be assessed by a doctor for causes of infertility.

Medicines known to induce the hepatic cytochrome P450-3A4 system (e.g. rifampicin, carbamazepine or St. Johnu2019s 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 LUTIGES u00ae has not been assessed. However, LUTIGES u00ae 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: LUTIGES u00ae 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 LUTIGES u00ae 100 mg TID was 4,5 %, 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 LUTIGES u00ae 100 mg TID were 5,4 % and 1 %, respectively.

Breastfeeding: Detectable amounts of progesterone have been identified in the milk of mothers. Therefore, LUTIGES u00ae should not be used during lactation.

LUTIGES u00ae 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 LUTIGES u00ae 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 reactions in women treated with LUTIGES u00ae in the clinical trial distributed by system organ classes (SOCs) and frequency.

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

• Headache
• Dizziness
• Insomnia
• Fatigue

Gastrointestinal disorders

• Abdominal distension
• Abdominal pain
• Nausea
• Diarrhoea
• Constipation
• Vomiting

Skin and subcutaneous tissue disorders

• Urticaria
• Rash
• Hypersensitivity reactions

Reproductive system and breast disorders

• Uterine spasm
• Vulvovaginal disorders*
• Vaginal mycosis
• Breast disorders**
• Pruritus genital

General disorders and administration site

• Oedema peripheral

* Vulvovaginal disorders such as vulvovaginal discomfort, vaginal burning sensation, vaginal discharge, vulvovaginal dryness and vaginal haemorrhage, have been reported following use of LUTIGES u00ae, 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 medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8. To report any adverse reactions to Ferring, please contact us on +27 12 345 6358.

High doses of progesterone may cause drowsiness. Treatment of overdosage consists of discontinuation of LUTIGES u00ae together with institution of appropriate symptomatic and supportive care.