Dose

Adults

• Once daily injection of 25 mg from day of oocyte retrieval, usually until 12 weeks of confirmed pregnancy.
• As the indications for Lubion are restricted to women of child-bearing age, dosage recommendations for children and the elderly are not appropriate.

Lubion is given by subcutaneous (25 mg) or intramuscular (25 mg) injection.

Special populations

Elderly

• No clinical data have been collected in patients over age 65.

Renal and Hepatic impairment

• There is no experience with use of Lubion in patients with impaired liver or renal function.

Paediatric population

• The safety and efficacy of Lubion in children (0 to 18 years) has not been established
• There is no relevant use of Lubion in the paediatric population in the indication for luteal support as part of an Assisted Reproductive Technology (ART) treatment program in infertile women.

Method of administration

• Treatment with Lubion should be initiated under the supervision of a physician experienced in the treatment of fertility problems.
• Lubion is intended for intramuscular or subcutaneous administration. Intramuscular administration
• Choose an appropriate area (femoral quadriceps of the right or left thigh). Swab proposed area, insert a deep injection (needle at an angle of 90°). The product should be injected slowly to minimise local tissue damage.
• Subcutaneous administration
• Choose an appropriate area (front of thigh, lower abdomen), swab proposed area, pinch the skin together firmly and insert the needle at an angle of 45° to 90°. The product should be injected slowly to minimise local tissue damage.

Contraindications

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

• Hypersensitivity to progesterone 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
• A history of idiopathic jaundice severe pruritus or pemphigoid gestationis during pregnancy

Special warnings and precautions for use

• 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.
• 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.

Interaction with other medicinal products and other forms of interaction

• 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.
• 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 Lubion has not been assessed. Concomitant use with other drugs is not recommended.

Fertility, pregnancy and lactation

Fertility

• Lubion is used in the treatment of some forms of infertility.

Pregnancy

• Lubion is indicated for luteal support as part of an Assisted Reproductive Technology (ART) treatment program in 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

• Progesterone is excreted in human milk and Lubion should not be used during breast-feeding.

Effects on ability to drive and use machines

Lubion 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 those operating machinery.

Special precautions for storage

• Store below 25°C. Do not refrigerate or freeze.
• Store in the original package in order to protect from light.

Side effects

• pain and swelling at injection site,
• breast tenderness,
• headache,
• weight gain or loss,
• acne,
• nausea,
• increased body or facial hair,
• loss of scalp hair,
• drowsiness, or
• dizziness.

Tell your doctor right away if you have serious side effects from progesterone injection including:

• unusual vaginal bleeding/discharge (e.g., breakthrough bleeding, spotting),
• stopped menstrual periods,
• breast lumps,
• swelling of the ankles or feet,
• mental/mood changes (e.g., depression, nervousness),
• dark patches on the skin or face,
• frequent or painful urination,
• dark urine,
• yellowing eyes or skin,
• stomach or abdominal pain, or
• persistent nausea and vomiting.

Pregnancy and Breastfeeding

• Progesterone injection is not recommended for use during pregnancy because it may harm a fetus, especially during the first 4 months of pregnancy. If you become pregnant or think you may be pregnant, tell your doctor. This drug passes into breast milk. Consult your doctor before breastfeeding.

References:

https://www.rxlist.com/progesterone-injection-side-effects-drug-center.htm#overview

https://www.drugs.com/international/prolutex-25mg.html

https://www.drugs.com/uk/lubion-25-mg-solution-for-injection-leaflet.html

https://www.pharmasure.co.uk/uploads/lubion-smpc.pdf

https://www.pharmasure.co.uk/video-guide-lubion/

https://www.mims.co.uk/drugs/obstetrics-and-gynaecology/infertility/lubion