Summary of Product Characteristics (SmPC) - Gestone 50 mg/ml solution for injection
1 NAME OF THE MEDICINAL PRODUCT
Gestone 50 mg/ml solution for injection
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ampoule contains progesterone, 100 mg in 2 ml.
Excipients with known effects: This medicinal product contains 200 mg benzyl alcohol in each ampoule, equivalent to 100 mg/ml (see section 4.4).
For the full list of excipients see Section 6.1.
3 PHARMACEUTICAL FORM
Solution for injection.
Clear, colourless to slightly yellow oily solution.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Gestone 50 mg/ml solution for injection is indicated for the treatment of dysfunctional uterine bleeding.
It is also indicated for the maintenance of early pregnancy in cases of documented history of 3 or more prior consecutive unexplained miscarriages and in selected cases as an adjunct to successful treatment of infertility with techniques such as in-vitro fertilisation (IVF) or gamete intra-fallopian transfer (GIFT) in order to facilitate uterine implantation of the fertilised ovum.
4.2 Posology and method of administration
Posology
Dysfunctional uterine bleeding
5 – 10 mg daily for 5 - 10 days until 2 days before anticipated onset of menstruation.
Maintenance of pregnancy
Twice weekly or more frequent (maximum: daily) injections of 25-100 mg from approximately day 15, or day of transfer of embryo or gametes usually until 8 - 16 weeks of pregnancy when secretion of progesterone from the placenta should be established.
Daily dosage can be increased to 200 mg at the discretion of the physician.
Special Populations
The indications for Gestone 50mg/ml solution for injection are restricted to women of child-bearing age.
Elderly
Dosage recommendations for the elderly are not appropriate.
Paediatric population
Dosage recommendations for children are not appropriate.
Method of administration
For intramuscular use.
Gestone 50 mg/ml solution for injection is given by intramuscular injection. It should be injected deep into the buttock, rather than the thigh or deltoid, using a 1.5 inch (3.8cm) needle. This site has ample fat cells where a depot of progesterone can be formed for slow release.
4.3 Contraindications
Gestone 50 mg/ml solution for injection should not be used in individuals with any of the following conditions:
- Hypersensitivity to progesterone or to any of the excipients listed in section 6.1.
- Undiagnosed vaginal bleeding
- Known missed abortion or incomplete 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.
Contraindicated as a diagnostic test for pregnancy.
4.4 Special warnings and precautions for use
Gestone 50 mg/ml solution for injection 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 and renal disease.
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 or photosensitivity, hypertension, 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 Gestone 50 mg/ml solution for injection, the patient and her partner should be assessed by a doctor for causes of infertility or pregnancy complications.
Excipient with known effect:
Gestone 50 mg/ml Solution for Injection contains benzyl alcohol which may cause allergic reactions.
Gestone 50 mg/ml solution for injection contains benzyl alcohol, large amounts of benzyl alcohol can build up in the body causing metabolic acidosis. Therefore, Gestone 50 mg/ml solution for injection must be used with caution in patients who have liver or kidney disease and those who are breast-feeding (also refer to section 4.6 Fertility, pregnancy and lactation - Gestone 50 mg/ml solution for injection is not recommended for use during lactation).
4.5 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 (see section 4.4).
Progestogens may inhibit ciclosporin metabolism leading to increased plasma ciclosporin concentrations and a risk of toxicity
Gestone 50 mg/ml solution for injection may interfere with the effects of bromocriptine.
The effect of concomitant injectable products on the exposure of progesterone from Gestone 50 mg/ml solution for injection has not been assessed. Concomitant use with other drugs is not recommended.
Gestone 50 mg/ml solution for injection may affect the results of laboratory tests of hepatic and/or endocrine functions.
4.6 Fertility, pregnancy and lactation
Gestone 50 mg/ml solution for injection may be used to maintain pregnancy where there is deficient production of endogenous progesterone from the corpus luteum. It should not be necessary to administer Gestone 50 mg/ml solution for injection once there is adequate secretion of placental progesterone. Gestone 50 mg/ml solution for injection contains progesterone itself, the same as the naturally secreted hormone, and is not associated with masculinisation of a female foetus as are synthetic progestins.
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 clinical trials with other drugs in this class of medicines, were comparable with the event rate described in the general population although the total exposure is too low to allow conclusions to be drawn.
Progesterone is excreted in human milk and Gestone 50 mg/ml solution for injection should not be used during breast-feeding.
4.7 Effects on ability to drive and use machines
Gestone 50 mg/ml solution for injection 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.
4.8 Undesirable effects
The most frequently reported adverse drug reactions are administration site reactions, breast and vulvo-vaginal disorders.
Frequencies reported are as follows:
Very Common (≥ 1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Not known (cannot be estimated from the available data).
| System Organ Class | Very common (≥ 1/10) | Common (≥ 1/100 to < 1/10) | Uncommon (≥ 1/1,000 to < 1/100) | Not known (cannot be estimated from the available data) |
| Psychiatric disorders | Mood altered | Depression | ||
| Nervous system disorders | Headache | Dizziness Somnolence | Insomnia | |
| Gastrointestinal disorders | Abdominal distension Abdominal pain Nausea Vomiting Constipation | Gastrointestinal disturbances | ||
| Skin and subcutaneous tissue disorders | Pruritus Rash | Urticaria Acne Hirsutism Alopecia Chloasma | ||
| Hepatobiliary disorders | Jaundice Pyrexia | |||
| Immune system disorders | Allergic reaction | |||
| Metabolism and nutrition disorders | Catabolism increased |
| System Organ Class | Very common (≥ 1/10) | Common (≥ 1/100 to < 1/10) | Uncommon (≥ 1/1,000 to < 1/100) | Not known (cannot be estimated from the available data) | ||
| Reproductive system and breast disorders | Uterine spasm Vaginal haemorrhage | Breast tenderness Breast pain Vaginal discharge Vulvo-vaginal pruritus Vulvo-vaginal discomfort Vulvo-vaginal inflammation OHSS | Breast disorders | Menstrual disturbances Premenstrual like syndrome Breakthrough bleeding Amenorrhoea | ||
| General disorders and administration site conditions | Administration site reactions* | Injection site | Feeling hot Malaise Pain | Weight gain Anaphylactoid reaction Oedema | ||
| haematoma | ||||||
| Injection site | ||||||
| induration | ||||||
| Fatigue | ||||||
*Administration site reactions, such as irritation, pain, pruritus and swelling 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 MHRA Yellow Card scheme (website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store).
4.9 Overdose
High doses of progesterone may cause drowsiness.
Treatment of overdose consists of discontinuation of Gestone 50 mg/ml solution for injection together with initiation of appropriate symptomatic and supportive care.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
ATC code: G03DA04
Gestone 50 mg/ml solution for injection is natural progesterone. Progesterone is a progestogen, the main hormone of the corpus luteum and the placenta. It acts on the endometrium by converting the proliferating phase to the secretory phase.
5.2 Pharmacokinetic properties
When given intramuscularly, the injection provides depot therapy.
5.3 Preclinical safety data
There are no preclinical data of relevance to the Prescriber which are additional to those already included in other sections of the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Ethyl oleate BP
Benzyl alcohol
6.2 Incompatibilities
None applicable.
6.3 Shelf life
2 years
6.4 Special precautions for storage
Store below 25°C. Store in the original package in order to protect from light.
6.5 Nature and contents of container
A pack contains 10 x 2 ml clear glass ampoules in a cardboard carton.
6.6 Special precautions for disposal
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Nordic Pharma Limited,
Building 1410, Arlington Business Park
Theale, Reading
RG7 4SA
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 05827/0025
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
25th March 2003
10 DATE OF REVISION OF THE TEXT
21/09/2026