LUBION Solution for injection Ref.[28021] Active ingredients: Progesterone

Lubion should be discontinued if any of the following conditions are suspected: myocardial infarction, cerebrovascular disorders, arterial or venous thromboembolism, thrombophlebitis, or retinal thrombosis.

Caution is indicated 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 (see section 4.5).

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 oedema or retinal haemorrhage.

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

Before starting treatment with Lubion, the patient and her partner should be assessed by a doctor for causes of infertility or pregnancy complications.

Drugs known to induce the hepatic cytochrome-P450-3A4 system (e.g. rifampicin, carbamazepine, griseofulvin, phenobarbital, phenytoin 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.

Since progesterone can influence diabetic control an adjustment in antidiabetic dosage could be required (see section 4.4). Progestogens may inhibit ciclosporin metabolism leading to increased plasma-ciclosporin concentrations and a risk of toxicity.

The effect of concomitant injectable products on the exposure of progesterone from Lubionhas not been assessed. Concomitant use with other drugs is not recommended.

Fertility

Lubion is used in the treatment of some forms of infertility (see section 4.1 for full details).

Pregnancy

Lubion is indicated for luteal support as part of an Assisted Reproductive Technology (ART) treatment programin infertile women.

There is limited and inconclusive data on the risk of congenital anomalies, including genital abnormalities in male or female infants, following intrauterine exposure during pregnancy. The rates of congenital anomalies, spontaneous abortion and ectopic pregnancies observed during the clinical trial were comparable with the event rate described in the general population although the total exposure is too low to allow conclusions to be drawn.

Breastfeeding

Progesteroneis excreted in human milk and Lubionshould not be used during breast-feeding.

Lubionhas 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 those operating machinery.

The most frequently reported adverse drug reactions during treatment with Lubionduring clinical trial are administration site reactions, breast and vulvo-vaginal disorders.

The table below displays the main adverse drug reactions in women treated with Lubion in the pivotal clinical trial. Data is expressed by system organ class (SOC) and frequency.

^* Administration site reactions, such as irritation, pain, pruritus and swelling.

Class effects

The following disorders although not reported by patients in clinical studies using Lubionhave been described with other drugs in this class of medicines.

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 national reporting system listed in Appendix V.

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.