Dimetriose

1. Name Of The Medicinal Product

Dimetriose

2. Qualitative And Quantitative Composition

Gestrinone 2.5mg capsule

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Hard white, size no. 4 gelatin capsules containing a white to slightly yellow powder. The capsule will be printed ”roussel” and logo.

4. Clinical Particulars

4.1 Therapeutic Indications

Therapeutic treatment of endometriosis.

4.2 Posology And Method Of Administration

Adults:-

Gestrinone is for oral administration to adult females only.

The dose is one capsule twice a week. To ensure that pregnant patients are not treated, it is essential that the first dose is taken on the first day of the menstrual cycle.

The second dose should be taken three days later. Thereafter, gestrinone capsules should be taken on the same two days of the week (preferably at the same time) every week for the duration of the treatment, which will normally be six months.

Should one dose be missed, then a capsule should be taken as soon as possible and the original sequence maintained.

Should two or more doses be missed, treatment should be discontinued and therapy re-started on the first day of the new cycle, following a negative pregnancy test and according to the usual dosage schedule.

Children & Elderly Adults :-

Treatment with gestrinone is not appropriate.

4.3 Contraindications

1. Known hypersensitivity to gestrinone or to any of the excipients

2. Pregnancy.

3. Lactation.

4. Severe cardiac, renal or hepatic insufficiency.

5. Metabolic and/or vascular disorders during previous oestrogen and/or progestogen therapy.

4.4 Special Warnings And Precautions For Use

1. The possibility of pregnancy must be ruled out before starting treatment, especially in the case of pre-existing amenorrhoea.

Gestrinone, at the recommended dose, may inhibit ovulation in some women, but pregnancies can occur with this treatment and gestrinone must not be relied on for contraception.

As concurrent administration of oral contraceptives may modify the action of gestrinone, it is, therefore, essential that barrier methods are used throughout treatment as the use of gestrinone is totally contra-indicated in pregnancy.

2. Because gestrinone may occasionally cause some degree of fluid retention, patients with cardiac or renal dysfunction require close monitoring.

3. Monitor ALAT, ASAT, cholesterol fractions in hyperlipidaemic subjects and blood sugar levels in diabetics.

4. Gestrinone will cause a decrease in the concentration of thyroid-binding globulin. Hence there will be a decrease in serum total levothyroxine levels. This is without clinical significance as free levothyroxine levels remain within the reference range as do thyroid-stimulating hormone levels.

5. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Concomitant administration of anti-epileptic drugs or rifampicin may result in accelerated metabolism of gestrinone.

4.6 Pregnancy And Lactation

Gestrinone is specifically contraindicated in pregnancy and lactation.

Administration should be discontinued if a patient is found to be pregnant as animal studies have shown embryotoxicity in some species, albeit at doses well in excess of those used clinically.

The possibility of pregnancy must be ruled out before starting treatment.

4.7 Effects On Ability To Drive And Use Machines

There is no evidence that gestrinone directly impairs the ability to drive or to operate machines.

4.8 Undesirable Effects

Spotting has been reported in some patients both during the first few weeks and throughout treatment.

Acne, oily skin, fluid retention, weight gain, hirsutism, voice change, hair loss and other androgen-type effects have been reported by some patients.

Other unwanted reactions recorded during gestrinone therapy include transient increases in liver transaminases, headache, gastro-intestinal disturbance, change in libido, hot flushes, decrease in breast size, nervousness and depression, cramp, change in appetite, arthralgia and isolated cases of benign intracranial hypertension.

4.9 Overdose

Acute toxicity studies in animals indicate that serious reactions are unlikely as an immediate results of a single excessive dose.

In the case of acute dosage, the drug should be removed by emesis or gastric lavage if ingestion is recent and the patient kept under observation in case of delayed reaction.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Antigonadotrophin, ATC code: G03XA02

Gestrinone, a synthetic steroid hormone, is an antiprogestin: it is not an oestrogen-progestogen combination. Gestrinone has an inhibitory effect on endometrial tissue. It is believed to act by direct inhibition of the synthesis-release mechanisms of pituitary gonadotrophins and a direct antagonist action on endometrial tissues.

5.2 Pharmacokinetic Properties

Gestrinone shows linear pharmacokinetics after oral administration of 1.25mg, 2.5 or 5mg. The peak concentration appears between 2.8 and 3.1 hours after administration.

The plasma half life is about 24 hours.

Three days after administration blood levels are only 5% of the maximum plasma concentration. The steady state is reached by the second administration, which is three days after the initial dose, therefore there is virtually no risk of accumulation under normal conditions of use.

Investigation of the absolute bioavailability in a subject after gestrinone administration demonstrates that after oral administration, absorption is virtually complete and first pass metabolism is negligible.

Gestrinone undergoes important hepatic metabolism, essentially through hydroxylation processes, resulting in the formation of conjugated metabolites.

5.3 Preclinical Safety Data

There are no preclinical data of relevance which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

The product contains Colloidal Silicon Dioxide, Maize Starch, Microcrystalline Cellulose, Lactose, Magnesium Stearate, and Talc.

The white opaque capsule shell contains Titanium Dioxide (BP) and Gelatin BP.

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

5 years

6.4 Special Precautions For Storage

Store below 25°C protected from light.

6.5 Nature And Contents Of Container

Dimetriose capsules are supplied in blister packs of 8 capsules.

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Sanofi-aventis

One Onslow Street

Guildford

Surrey, GU1 4YS, UK

8. Marketing Authorisation Number(S)

PL 04425/0311

9. Date Of First Authorisation/Renewal Of The Authorisation

07 November 2007

10. Date Of Revision Of The Text

6 February 2008

Legal category: POM