8, Akanbi-Onitiri Crescent, Off Eric Moore Road, Surulere, Lagos. Lagos.
Tel: 234-1-5875179, 5874082, 5877689; 90405798
Laboratories Serono SA., 1170, Aubonne, Switzerland.
Dosage Form, Composition & NAFDAC Registration Number (NRN)
Injections (NRN: 04-2029): Each ampoule of Metrodin HP contains Urofollitrophin (FSH) 75, 150 IU. Lactose (excipient) 10 mg.
How to identify the Product: Powder for reconstitution in ampoules plus 1 mL solvent.
Pack Size: Ampoules of Metrodin HP are packed singly and in boxes of ten. Each ampoule is accompanied by an ampoule of 1 mL of physiologic Sodium Chloride injection as solvent.
Ampoules of Metrodin HP contain Urofollitrophin (FSH) as a white freeze dried powder. Two strengths are available: 75 and 150 IU. Each ampoule of Metrodin HP is accompanied by a solvent ampoule containing 1 mL of Isotonic, sterile and pyrogen free Sodium Chloride Injection solution
Metrodin HP contains a highly purified hormone obtained form Human menopausal urine, having only FSH activity. Human menopausal gonadotrophin (HMG) exerts FSH and LH activities. For this reason, HMG is indicated in hypogonadotrophic hypopituitarism (WHO Group 1 patients) where both gonadotrophin stimulations are needed.
In patients showing normal or high LH levels (WHO Group II), selective FSH deficiencies require availability of preparations without LH activity; this characteristic belongs to FSH. FSH stimulates both the growth and the maturation of follicles, it induces the secretion of oestrogens and a proliferation of the endometrium.
Metrodin HP is indicated for stimulation of follicular growth in infertile women. A course of Metrodin HP is usually followed by human chorionic gonadotrophin (hCG, Profasi) to induce ovulation.
Metrodin HP is used:
a) For single follicular development in cases such as hypothalamic pituitary dysfunction (WHO Group II classification), including patients with polycystic ovarian disease.
b) For multiple follicular development (assisted conception techniques); in cases such as tubal occlusion, unexplained infertility and male factor infertility.
Cases of prior hypersensitivity to menotrophins; Pregnancy; Ovarian enlargement or cyst not due to polycystic ovarian syndrome; Gynaecological haemorrhage of unknown aetiology; Ovarian, uterine or mammary carcinoma.
Metrodin HP is contraindicated when an effective response cannot be obtained such as: Primary ovarian failure (ovarian dysgenesis, premature menopause); Malformations of sexual organs incompatible with pregnancy; Fibroid tumours of the uterus incompatible with pregnancy.
Before starting treatment, the couple's infertility should be assessed as appropriate and putative contra-indications for pregnancy evaluated. Adherence to the recommended dosage and monitoring schedules will minimise the possibility of ovarian hyperstimulation syndrome. In clinical trials, the prevalence of severe ovarian hyperstimulation syndrome was found to be less than 1%.
Excessive ovarian response to Metrodin HP treatment does generally not induce significant adverse effects except if hCG is administered for ovulation induction or if pregnancy occurs; ovarian hyperstimulation syndrome occurs usually 1 to 2 weeks following hCG administration and ovulation.
In case of symptoms such as pelvic pain, abdominal distension, or ovarian enlargement or if oestrogen assays or ultra sound examination suggest an excessive oestrogen assays response, Metrodin HP administration should be discontinued and hCG should not be administered and intercourse avoided in order to prevent ovarian hyperstimulation.
Ascites, pericardial effusion, hydrothorax, haemoconcentration, secondary hyperaldosteronism or hypercoagulability might appear. These symptoms should be controlled through appropriate medical measure, including avoidance of unnecessary pelvic examination. In the absence of pregnancy, they usually resolve spontaneously with the onset of the menses. It is important to consider the effect of the lactose component of Metrodin HP if administered to lactose-sensitive patients.
No clinically significant adverse drug interactions have been reported during Metrodin HP therapy. Concomitant use of Metrodin HP and clomiphene citrate may potentiate the follicular response, whereas concurrent use of GnRH agonist-induced pituitary desensitisation may increase the dosage of Metrodin HP needed to elicit an adequate ovarian response.
No drug incompatibilities have been reported for Metrodin HP. Metrodin HP should not be mixed with other drugs in the same syringe.
Local reactions at the injection site, fever and arthralgia have been reported following urofollitrophin and menotrophins administration. Gastro-intestinal symptoms may occur as well as bloating of the stomach, pelvic pain or sore breasts.
Mild to moderate ovarian enlargement, ovarian cysts may be observed. Severe hyperstimulation syndrome is rare (see "Warnings"). In rare instances, arterial thromboembolism has been associated with menotrophin human chorionic gonadotrophin therapy. This may also occur with Metrodin HP/Profasi therapy.
The incidence of multiple births following Metrodin HP/Profasi therapy treatment in a minority of cases. The majority of multiple conceptions have been found to be twins. In IVF, it is related to the number of embryos replaced. Pregnancy wastage by miscarriage or abortion is comparable with the rates in women with other fertility problems. Ectopic pregnancy may occur in women with a history of prior tubal disease.
Dosage & Administration
Metrodin HP is intended for subcutaneous or intramuscular administration. The powder should be reconstituted immediately prior to use with the solvent provided. In order to avoid the injection of large volumes, up to 5 ampoules of Metrodin HP may be dissolved in 1 ml of solvent.
Women with hypothalamic-pituitary dysfunction who present with either oligomenorrhoea or amenorrhoea (WHO Group II):
The object of Metrodin HP therapy is to develop a single mature Graafian follicle from which the ovum will be liberated after the administration of Profasi. Metrodin HP may be given as a course of daily injections. In menstruating patients, treatment should commence within the first 7 days of the menstrual cycle.
Treatment should be tailored to the individual patient's response. A commonly used regimen commences at 75 - 150 IU FSH daily and may be increased or decreased by up to 75 IU/day at 7 or 14 days intervals if necessary to obtain an adequate but not excessive response. If patient fails to respond adequately after 4 weeks of treatment, that cycle should be abandoned.
When an optimal response is obtained, a single intramuscular injection of up to 10,000 IU Profasi should be administered 24 - 48 hours after the last Metrodin HP injection. The patient is recommended to have coitus on the day of and that following Profasi administration. If an excessive response is obtained, treatment should be stopped and Profasi withheld (see "Precautions/Warnings"). Treatment should recommence in the next cycle at a dosage lower than that of the previous cycle.
Women undergoing superovulation for in vitro fertilisation and other assisted conception techniques:
A regimen for superovulation involves the administration of 150-225 IU of Metrodin HP daily, commencing on days 2 or 3 of the cycle. Treatment is continued, with the dose adjusted (to a maximum of 450 IU daily) according to the patient's response, until adequate follicular development has been achieved. A single injection of up to 10,000 IU Profasi is administered 24 - 48 hours after the last Metrodin HP injection to induce final follicular maturation.
Down-regulation with a GnRH agonist is now commonly used in order to suppress the endogenous LH surge and to control tonic levels of LH. In a commonly used protocol, Metrodin HP is started approximately 2 weeks after the start of agonist treatment, both being continued until adequate follicular development is achieved.
For example, 225 IU Metrodin HP are administered (subcutaneous or intramuscular) for the first 7 days. The dose is then adjusted according to the ovarian response.
Ampoules of Metrodin HP should be stored below 25oC and should not be used after the expiry date stated on the package. Solutions of Metrodin HP reconstituted in physiologic sodium chloride should be used immediately after preparation.