DAILY SUBCUTANEOUS INJECTION
Vials containing freeze-dried powder
Triptorelin, presented as acetate .. ... ... .. ... ... ... ... ... ... ... .............. ... ... 0.1 mg
Mannitol ... ... ... ...... ... ... ....... ... ... ... ... ... ... .... ... ... ... ………………….. 10 mg
Ampoule of solvent
Sodium chloride ...... ... ... ... ……... ... ... ... ... ... ... ............................ ... ... .. 9 mg
Water for injection ... ... ... ... ... .... ... ... ... ... ... ... ... ... ... ... ... ... ... .. q.s. 1.00 ml
PHARMACEUTICAL FORM: Powder and solvent for solution for injection (S.C.).
PRESENTATION: Box contains 7 vials of freeze-dried powder (lyophilization) and 7 ampoules of solvent.
THERAPEUTIC INDICATIONS: This drug is an analogue of a natural hormone. It is used:
- In women: In the treatment of infertility in combination with other hormones (hormones gonadotropins) when used by in vitro fertilization (IVFET).
- In man: Prostate cancer with metastases (attack treatment, before use of the sustained release form).
POSOLOGY AND METHOD OF ADMINISTRATION
Strictly comply with your doctor’s prescription
Prostate cancer: One daily injection of 0.1 mg triptorelin by subcutaneous route from Day 1 to 7, before changing to the sustained release form.
Female infertility: In combination with gonadotropins. One daily subcutaneous injection from Day 2 of the menstrual cycle (at the same time as ovarian stimulation stars) until the day before the day set for induction, i.e.an average period of 10 to 12 days for each attempt.
CONTRAINDICATIONS Hypersensitivity to GnRH; its analogues or to one of the constituents.
SPECIAL WARNINGS AND SPECIAL PRECAUTIONS FOR USE
Warnings on starting the treatment: It has been reported the clinical symptoms (particularly bone pain) may worsen on starting the treatment but these cases are isolated and generally transient. These cases merit particularly attentive medical supervision over the first few weeks of treatment, notably in patients presenting obstructed urinary tracts and in those with spinal metatases (see Undesirable effects). For the same reason, particular care should be taken when starting treatment in patients with premonitory signs of medullary compression. A transitory increase in acid phosphatases may be observed at the start treatment.
Precautions for use: It may be advantageous to check blood testosterone levels periodically as these should not exceed 1 ng/ml.
Warnings: Confirm that the patient is not pregnant before prescription of Diphereline 0.1 mg. The follicular retrieval induced by the injections of triptorelin combined with gonadotropins may increase markedly in some predisposed patients and particularly in cases of polycystic ovarian disease. The ovarian response to the triptorelin-gonadotropin combination may differ with the same does from one patient to another one, and in certain cases, from one cycle to another in the same patient.
Precautions for use:
The induced ovulation should be monitored under rigorous medical supervision with strict and regular biological and clinical controls: fast plasma oestrogen assay and ultrasonography (see Undesirable effects). If the ovarian response is excessive, it is recommended to interrupt the stimulation cycle by discontinuing the gonadotropin injections.
PREGNANCY AND LACTATION
At the present time, GnRH analogues are used in combination with gonadotropins to induce ovulation and therefore encourage pregnancy. Pregnancy is therefore not an indication for these products. However, experience has shown that after ovulation has been induced in a previous cycle, some women become pregnant without realizing it, and undertake a further course to stimulate ovulation. This product should not be used during pregnancy and breast feeding.
As a general rule, when you are pregnant or breast feeding, you should always tell your doctor or pharmacist before using any medicine.
INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHER FORMS OF INTERACTION: No clinically significant interaction with other medicinal products has been reported.
At the start of treatment (see Special warning and special precautions for use)
Urinary symptoms, bone pain of metastatic origin and symptoms associated with medullary compression from spinal metastases may be exacerbated when plasma testosterone is initially and transiently increases at the start of the treatment. These symptoms disappear in one to two week.
During the treatment: The most frequently reported undesirable effects (hot flushes, decreased libido, and impotence) are related to the decreased plasma testosterone levels resulting from the pharmacological effects of the substance, and are similar to those observed with other GnRH analogues. These effects have not been observed during short-term treatment with Diphereline 0.1 mg.
At the start of the treatment: When used to treat infertility, the combination with gonadotropin may result in ovarian hyperstimulation. Ovarian hypertrophy, pelvis and/or abdominal pains may be observed (see Special warning and special precautions for use).
During the treatment: The most frequently reported effects, such as hot flushes, vaginal dryness, decreased libido and dyspareunia, are related to pituitary-ovarian blockade. These effects have not been observed during short-term treatment with Diphereline 0.1 mg. A few rare cases of headache, arthralgia and myalgia have been reported.
In both men and women:
Allergic reactions such as urticaria, rash, pruritus and very occasionally Quincke’s oedema have been reported. A few cases of nausea, vomiting, weight gain, hypertension, mood disorders, visual disturbances, pain at the injection site and fever have been reported. The prolonged use of GnRH analogues may lead to bone loss, a risk factors for possible osteoporosis. These effects have not been observed during short-term treatment with Diphereline 0.1 mg.
Inform your doctor any undesirable effect occurred during therapy
Triptorelin is a synthetic decapeptide analogue of natural GnRH (gonadotropin-releasing hormone). Studies conducted in humans and in animals have shown that after initial stimulation, the prolonged administration of triptorelin inhibits gonadotrope secretion with consequent suppression of testicular and ovarian function.
Further studies in animals have suggested another mechanism of action: direct on the gonadotrophins by decreasing the sensitivity of peripheral receptors to GnRH.
Prostate cancer: The administration of a daily dose of triptorelin may initially increase LH and FSH blood levels and may consequently increase initial testosterone levels (flare up). Continuing the treatment decreases LH and FSH levels to concentration that result in castration levels of steroids within 2-3 weeks and for as long as the product is administered. The treatment may improve functional and objective symptoms.
Female infertility: Prolonged treatment with triptorelin inhibits gonadotrope secretion (FSH and LH). The treatment ensured therefore the suppression of the intercurrent endogenous LH peak enabling enhanced quality of folliculogenesis and increased follicular retrieval.
In healthy adult volunteers: Following subcutaneous injection the resorption of triptorelin (0.1 mg) is quick (tmax = 0.63 ± 0.26 hr) with a peak plasma concentration (Cmax = 1.85 ± 0.23 ng/ml). Elimination is achieved with a biological half-life of 7.6 ± 1.6 hr, after 2 3 to 4 hours distribution phase.
Total plasma clearance is: 161 ± 28 ml/min. Distributionvolume is: 156 ± 158 ml/kg.
In patients with prostate cancer: With subcutaneous administration (0.1 mg), plasma concentrations oscillate between maximum value of 1.28 ± 0:24 ng/ml (Cmax) usually obtained one hour after injection ( tmax) and minimum values of 0:28 ± 0.15 ng/ml (Cmin) obtained 24 hours after injection. Biological half-life is on average 11.7 ± 3.4 hr but varies according to patients, and plasma clearance (118 ± 32 ml/min.) reflects slowing of elimination in these patients, whilst distribution volumes are close to those of healthy volunteers (1130 ± 210 ml/kg).
OVERDOSAGE: Not applicable
STORAGE: For temperatures below 25°C, away from heat sources.
KEEP OUT OF REACH OF CHILDREN SHELF LIFE: 2 years from date of manufacture
DO NOT EXCEED THE EXPRIRY DATE PLAINLY INDICATED ON THE PACKAGING
COUNTRY OF ORIGIN: FRANCE
READ CAREFULLY INSTRUCTIONS BEFORE USE PLEASE CONSULT YOUR DOCTOR FOR FURTHER INFORMATION PRESCRIPTIONS ITEM ONLY
French Marketing Authorization Number: 328 502-6
IPSEN PHARMA BIOTECH Parc d'Activité du Plateau de Signes-Chemin Départemental No.402-83870 SINGES – FRANCE
Ipsen Pharma 65, quai Georges Gorse, 92100 Boulogne Billancourt - France