Menopur

Menopur

menotrophin

Manufacturer:

Ferring

Distributor:

DCH Auriga - Universal
/
Four Star
Full Prescribing Info
Contents
Highly-purified menotrophin corresponding to FSH and LH.
Description
Each 75-IU vial contains highly-purified menotrophin [human menopausal gonadotrophin (HMG)] corresponding to follicle-stimulating hormone (FSH) 75 IU and luteinizing hormone (LH) 75 IU.
Each multidose 600-IU vial with powder contains highly purified menotrophin (HMG) corresponding to FSH 600 IU and LH 600 IU. After reconstitution, 1 mL of the reconstituted solution contains highly purified menotrophin 600 IU.
Each multidose 1,200-IU vial with powder contains highly purified menotrophin (HMG) corresponding to FSH 1,200 IU and LH 1,200 IU. After reconstitution, 1 mL of the reconstituted solution contains highly purified menotrophin 600 IU.
Excipients/Inactive Ingredients: 75 IU: Powder: Lactose and sodium hydroxide for pH adjustment. Solvent: Isotonic sodium chloride solution with dilute hydrochloric acid for pH adjustment.
600 and 1,200 IU: Powder: Lactose monohydrate, polysorbate 20, disodium phosphate heptahydrate and phosphoric acid (for pH adjustment). Solvent: Metacresol and water for injection.
Human chorionic gonadotrophin (hCG), a naturally occurring hormone in postmenopausal urine, is present in Menopur and is the main contributor of the LH activity.
The highly purified menotrophin is obtained from the urine of postmenopausal women.
Action
Pharmacotherapeutic Group: Gonadotrophins. ATC Code: G03G A02.
Pharmacology: Pharmacodynamics: Menopur is produced from the urine of postmenopausal women. Human chorionic gonadotrophin (hCG), a naturally occurring hormone in postmenopausal urine, is present in Menopur and is the main contributor of the LH activity.
Menotrophin, which contains both FSH and LH activity, induces ovarian follicular growth and development as well as gonadal steroid production in women who do not have primary ovarian failure. FSH is the primary driver of follicular recruitment and growth in early folliculogenesis, while LH is important for ovarian steroidogenesis and is involved in the physiological events leading to the development of a competent pre-ovulatory follicle. Follicular growth can be stimulated by FSH in the total absence of LH, but the resulting follicles develop abnormally and are associated with low oestradiol levels and inability to luteinize to a normal ovulatory stimulus.
In line with the action of LH activity in enhancing stereoidogenesis, oestradiol levels associated with treatment with Menopur are higher than with recombinant FSH preparations in down-regulated in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) cycles. This issue should be considered when monitoring patient’s response based on oestradiol levels. The difference in oestradiol levels is not found when using low-dose ovulation induction protocols in anovulatory patients.
Pharmacokinetics: The pharmacokinetic profile of the FSH in Menopur has been documented. After 7 days of repeated dosing with Menopur 150 IU in down-regulated healthy female volunteers, maximum plasma FSH concentrations (baseline-corrected) (mean±SD) were 8.9±3.5 IU/L and 8.5±3.2 IU/L for the SC and IM administration, respectively. Maximum FSH concentrations were reached within 7 hrs for both routes of administration. After repeated administration, FSH was eliminated with a half-life (t½) (mean±SD) of 30±11 hrs and 27±9 hrs for the SC and IM administration, respectively. Although the individual LH concentration versus time curves show an increase in the LH concentration after dosing with Menopur, the data available were too sparse to be subjected to a pharmacokinetic analysis.
Menotrophin is excreted primarily via the kidneys.
The pharmacokinetics of Menopur in patients with renal or hepatic impairment has not been investigated.
Indications/Uses
Treatment of infertility in the following clinical situations: Anovulation, including polycystic ovarian disease (PCOD), in women who have been unresponsive to treatment with clomiphene citrate; controlled ovarian hyperstimulation to induce the development of multiple follicles for assisted reproductive technologies (ART) [eg, in vitro fertilisation/embryo transfer (IVF/ET), gamete intra-fallopian transfer (GIFT) and intracytoplasmic sperm injection (ICSI)].
Dosage/Direction for Use
Treatment with Menopur should be initiated under the supervision of a physician experienced in the treatment of fertility problems.
There are great interindividual variations in the response of the ovaries to exogenous gonadotrophins. This makes it impossible to set a uniform dosage scheme. The dosage should, therefore, be adjusted individually depending on the ovarian response. Menopur can be given alone or in combination with a GnRH agonist or antagonist.
Recommendations about dosage and duration of treatment may change depending on the actual treatment protocol.
Women with Anovulation (Including PCOD): The object of Menopur therapy is to develop a single Graafian follicle from which the oocyte will be liberated after the administration of hCG.
Menopur therapy should start within the initial 7 days of the menstrual cycle. The recommended initial dose of Menopur is 75-150 IU daily, which should be maintained for at least 7 days. Based on clinical monitoring (including ovarian ultrasound alone or in combination with measurement of oestradiol levels), subsequent dosing should be adjusted according to individual patient response. Adjustments in dose should not be made more frequently than every 7 days. The recommended dose increment is 37.5 IU/adjustment and should not exceed 75 IU. The maximum daily dose should not be >225 IU. If a patient fails to respond adequately after 4 weeks of treatment, that cycle should be abandoned and the patient should recommence treatment at a higher starting dose than in the abandoned cycle.
When an optimal response is obtained, a single injection of hCG 5,000-10,000 IU should be given 1 day after the last Menopur injection. The patient is recommended to have coitus on the day of and the day following hCG administration. Alternatively, intrauterine insemination (IUI) may be performed. If an excessive response to Menopur is obtained, treatment should be stopped and hCG withheld (see Precautions) and the patient should use a barrier method of contraception or refrain from having coitus until the next menstrual bleeding has started.
Women Undergoing Controlled Ovarian Hyperstimulation for Multiple Follicular Development for ART: In a protocol using down-regulation with a GnRH agonist, Menopur therapy should start approximately 2 weeks after the start of agonist treatment. In a protocol using down-regulation with a GnRH antagonist, Menopur therapy should start on day 2 or 3 of the menstrual cycle.
The recommended initial dose of Menopur is 150-225 IU daily for at least the first 5 days of treatment. Based on clinical monitoring (including ovarian ultrasound alone or in combination with measurement of oestradiol levels), subsequent dosing should be adjusted according to individual patient response and should not exceed >150 IU/adjustment. The maximum daily dose given should not be >450 IU daily and in most cases dosing beyond 20 days is not recommended.
When a suitable number of follicles have reached an appropriate size, a single hCG injection of up to 10,000 IU should be administered to induce final follicular maturation in preparation for oocyte retrieval. Patients should be followed closely for at least 2 weeks after hCG administration. If an excessive response to Menopur is obtained, treatment should be stopped and hCG withheld (see Precautions) and the patient should use a barrier method of contraception or refrain from having coitus until the next menstrual bleeding has started.
Administration: Menopur multidose 600 IU and 1,200 IU are intended for SC injection after reconstitution with the solvent provided. The powder should be reconstituted prior to use. The reconstituted solution is for multiple injections and can be used for up to 28 days.
Shaking should be avoided. The solution should not be used if it contains particles or if it is not clear.
Overdosage
The effects of an overdose is unknown, nevertheless one could expect ovarian hyperstimulation syndrome to occur (see Precautions).
Contraindications
Hypersensitivity to menotrophin or to any of the excipients of Menopur.
Women who have: Tumours of the pituitary gland or hypothalamus; ovarian, uterine or mammary carcinoma; gynaecological haemorrhage of unknown aetiology; ovarian cysts or enlarged ovaries not due to polycystic ovarian disease.
In the following situations treatment outcome is unlikely to be favourable, and therefore, Menopur should not be administered: Primary ovarian failure; malformation of sexual organs incompatible with pregnancy; fibroid tumours of the uterus incompatible with pregnancy.
Use in pregnancy: Menopur is contraindicated in women who are pregnant.
There are no or limited amount of data from the use of menotrophins in pregnant women. No animal studies have been carried out to evaluate the effects of Menopur during pregnancy.
Use in lactation: Menopur is contraindicated in women who are lactating.
Special Precautions
Menopur is a potent gonadotrophic substance capable of causing mild to severe adverse reactions, and should only be used by physicians who are thoroughly familiar with infertility problems and their management.
Gonadotrophin therapy requires a certain time commitment by physicians and supportive health professionals, and calls for monitoring of ovarian response with ultrasound, alone or in combination with measurement of serum oestradiol levels, on a regular basis. There is considerable interpatient variability in response to menotrophin administration, with a poor response to menotrophin in some patients. The lowest effective dose in relation to the treatment objective should be used.
The 1st injection of Menopur should be performed under direct medical supervision.
Before starting treatment, the couple’s infertility should be assessed as appropriate and putative contraindications for pregnancy evaluated. In particular, patients should be evaluated for hypothyroidism, adrenocortical deficiency, hyperprolactinaemia and pituitary or hypothalamic tumours, and appropriate specific treatment given.
Patients undergoing stimulation of follicular growth, whether in the frame of a treatment for anovulatory infertility or ART procedures, may experience ovarian enlargement or develop hyperstimulation. Adherence to recommended Menopur dosage and regimen of administration and careful monitoring of therapy will minimise the incidence of such events. Acute interpretation of the indices of follicle development and maturation requires a physician who is experienced in the interpretation of the relevant tests.
Ovarian Hyperstimulation Syndrome (OHSS): Ovarian hyperstimulation syndrome is a medical event distinct from uncomplicated ovarian enlargement. Ovarian hyperstimulation syndrome is a syndrome that can manifest itself with increasing degrees of severity. It comprises marked ovarian enlargement, high serum sex steroids and an increase in vascular permeability which can result in an accumulation of fluid in the peritoneal, pleural and, rarely, in the pericardial cavities.
The following symptoms may be observed in severe cases of OHSS: Abdominal pain, abdominal distension, severe ovarian enlargement, weight gain, dyspnoea, oliguria and gastrointestinal symptoms including nausea, vomiting and diarrhoea. Clinical evaluation may reveal hypovolaemia, haemoconcentration, electrolyte imbalances, ascites, haemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress and thromboembolic events.
Excessive ovarian response to gonadotrophin treatment seldom gives rise to OHSS unless hCG is administered to trigger ovulation. Therefore, in cases of ovarian hyperstimulation, it is prudent to withhold hCG and advise the patient to refrain from coitus or to use barrier methods for at least 4 days. Ovarian hyperstimulation syndrome may progress rapidly (within 24 hrs to several days) to become a serious medical event, therefore, patients should be followed for at least 2 weeks after the hCG administration.
Adherence to recommended Menopur dosage, regimen of administration and careful monitoring of therapy will minimise the incidence of ovarian hyperstimulation and multiple pregnancy (see Dosage & Administration and Adverse Reactions). In ART, aspiration of all follicles prior to ovulation may reduce the occurrence of hyperstimulation.
Ovarian hyperstimulation syndrome may be more severe and more protracted if pregnancy occurs. Most often, OHSS occurs after hormonal treatment has been discontinued and reaches its maximum severity at about 7-10 days following treatment. Usually, OHSS resolves spontaneously with the onset of menses.
If severe OHSS occurs, gonadotrophin treatment should be stopped if still ongoing, the patient hospitalised and specific therapy for OHSS started.
This syndrome occurs with higher incidence in patients with polycystic ovarian disease.
Multiple Pregnancy: Multiple pregnancy, especially high order, carries an increased risk of adverse maternal and perinatal outcomes.
In patients undergoing ovulation induction with gonadotrophins, the incidence of multiple pregnancies is increased compared with natural conception. The majority of multiple conceptions are twins. To minimise the risk of multiple pregnancy, careful monitoring of ovarian response is recommended.
In patients undergoing ART procedures, the risk of multiple pregnancy is related mainly to the number of embryos replaced, their quality and the age of the patient.
The patient should be advised of the potential risk of multiple births before starting treatment.
Pregnancy Wastage: The incidence of pregnancy wastage by miscarriage or abortion is higher in patients undergoing stimulation of follicular growth for ART procedures than in the normal population.
Ectopic Pregnancy: Women with a history of tubal disease are at risk of ectopic pregnancy, whether the pregnancy is obtained by spontaneous conception or with fertility treatment. The prevalence of ectopic pregnancy after IVF has been reported to be 2-5%, as compared to 1-1.5% in the general population.
Reproductive System Neoplasms: There have been reports of ovarian and other reproductive system neoplasms, both benign and malignant, in women who have undergone multiple drug regimens for infertility treatment. It is not yet established if treatment with gonadotrophins increases the baseline risk of these tumours in infertile women.
Congenital Malformation: The prevalence of congenital malformations after ART may be slightly higher than after spontaneous conceptions. This is thought to be due to differences in parental characteristics (eg, maternal age, sperm characteristics) and multiple pregnancies.
Thromboembolic Events: Women with generally recognised risk factors for thromboembolic events eg, personal or family history, severe obesity (body mass index >30 kg/m2) or thrombophilia may have an increased risk of venous or arterial thromboembolic events, during or following treatment with gonadotrophins. In these women, the benefits of gonadotrophin administration need to be weighed against the risks. It should be noted however, that pregnancy itself also carries an increased risk of thromboembolic events.
Renal/Hepatic Impairment: Patients with renal and hepatic impairment have not been included in clinical trials (see Pharmacology: Pharmacokinetics under Actions).
Effects on the Ability to Drive or Operate Machinery: No studies on the effects on the ability to drive and use machines have been performed. However, Menopur is unlikely to have influence on the patient’s ability to drive and use machines.
Impairment of Fertility: Menopur is indicated for use in infertility (see Indications).
Use in children: There is no relevant use of Menopur in the paediatric population.
Use In Pregnancy & Lactation
Use in pregnancy: Menopur is contraindicated in women who are pregnant.
There are no or limited amount of data from the use of menotrophins in pregnant women. No animal studies have been carried out to evaluate the effects of Menopur during pregnancy.
Use in lactation: Menopur is contraindicated in women who are lactating.
Adverse Reactions
The most frequently reported adverse drug reactions during treatment with Menopur in clinical trials are OHSS, headache, abdominal pain, abdominal distension and injection site pain, with an incidence rate up to 5%.
The table, as follows, displays the main adverse drug reactions in women treated with Menopur in clinical trials distributed by system organ classes and frequency. Further, the adverse drug reactions seen during post-marketing experience are mentioned with unknown frequency.

Click on icon to see table/diagram/image
Drug Interactions
No interaction studies have been conducted with Menopur in humans.
Although there is no controlled clinical experience, it is expected that the concomitant use of Menopur and clomiphene citrate may enhance the follicular response. When using GnRH agonist for pituitary desensitisation, a higher dose of Menopur may be necessary to achieve adequate follicular response.
Incompatibilities: In the absence of compatibility studies, Menopur must not be mixed with other medicinal products.
Caution For Usage
Instructions for Use and Handling: The powder should only be reconstituted with the solvent provided in the package.
Menopur Multidose 600 IU and 1,200 IU: Attach the reconstitution needle to the pre-filled syringe. Inject the total contents of solvent into the vial containing the powder. Menopur 600 IU must be reconstituted with 1 pre-filled syringe with solvent before use. Menopur 1,200 IU must be reconstituted with 2 pre-filled syringes with solvent before use.
The powder should dissolve quickly to a clear solution. If not, roll the vial gently between the hands until the solution is clear. Shaking should be avoided.
The single use administration syringes with pre-fixed needle are graduated in FSH/LH units from 37.5-600 IU.
Draw up the reconstituted solution from the vial into the administration syringe for injection according to the prescribed dose and administer the dose immediately. Each mL of reconstituted solution contains FSH and LH 600 IU.
Each reconstituted Menopur multidose 600 IU or 1,200 IU vial should be for individual patient use only.
The reconstituted solution should not be administered if it contains particles or is not clear.
Any unused product or waste material should be disposed in accordance with local requirements.
Storage
Menopur 75: Store protected from light. Do not store above 30°C.
After dissolution in the included solvent, the solution should be administered immediately.
Menopur 600 & 1,200: Store in a refrigerator (2-8°C). Do not freeze. Store in the original container.
After reconstitution, the solution may be stored for a maximum of 28 days at not >25°C. Do not freeze.
Shelf-Life: Menopur 75: 2 years.
Menopur 600 & 1,200: 3 years.
ATC Classification
G03GA02 - human menopausal gonadotrophin ; Belongs to the class of gonadotropins. Used as ovulation stimulants.
Presentation/Packing
Powd for inj 75 IU (vial) x 10's + solvent (amp) x 10's. 600 IU (vial) x 1's + 1 mL solvent (pre-filled syringe) x 1's. 600 IU (vial) x 1's + 1 mL solvent (pre-filled syringe) x 2's.
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