Menotrophin for Injection BP 75 IU Taj Pharma

Menotrophin for Injection BP 75 IU

1. Name of the medicinal product

Menotrophin 75 IU powder and solvent for solution for injection BP Taj Pharma.
Menotrophin 150 IU powder and solvent for solution for injection BP Taj Pharma.

2. Qualitative and quantitative composition

Active ingredient

Each vial of powder contains:
Menotrophin (human menopausal gonadotrophin, HMG)
equvivalent human follicle stimulating hormone (FSH) 75 IU
human luteinising hormone (LH) activity                        75 IU
Excipients                                                                           q.s

Menotrophin (human menopausal gonadotrophin, HMG)
equvivalent human follicle stimulating hormone (FSH) 150 IU
human luteinising hormone (LH) activity                       150 IU
Excipients                                                                        q.s

Human Chorionic Gonadotrophin (hCG), a naturally occurring hormone in postmenopausal urine, is present in Menotrophin and contributes to the overall luteinizing hormone activity.

Menotrophin is produced from human urine.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Lyophilised Powder and solvent for solution for injection.

4. Clinical particulars

4.1 Therapeutic indications

Treatment of female and male infertility in the following groups of patients:

Anovulation, including polycystic ovarian disease (PCOD) in women who have been unresponsive to treatment with clomiphene citrate:

– Women undergoing controlled ovarian hyperstimulation: Menotrophin can induce the development of multiple follicles for assisted reproductive technologies (ART) (e.g. in vitro fertilisation/embryo transfer (IVF/ET), gamete intra-fallopian transfer (GIFT) and intracytoplasmic sperm injection (ICSI)).

– Hypogonadotrophic hypogonadism in men: Menotrophin may be given in combination with human chorionic gonadotrophin (e.g. Choragon) for the stimulation of spermatogenesis. Patients with primary testicular failure are usually unresponsive.

4.2 Posology and method of administration

Treatment with Menotrophin should be initiated under the supervision of a physician experienced in the treatment of fertility problems.

Posology

For intramuscular or subcutaneous use. The dosage regimens described below are identical for both forms of administration.

There are great inter-individual 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. Recommendations about dosage and duration of treatment may change depending on the actual treatment protocol.

Anovulatory infertility:

Menotrophin is administered to induce follicular maturation and is followed by treatment with chorionic gonadotrophin to stimulate ovulation and corpus luteum formation.

Menotrophin therapy should start within the initial 7 days of the menstrual cycle. The recommended initial dose of Menotrophin 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 per adjustment and should not exceed 75 IU. The maximum daily dose should not be higher than 225 IU. If a patient fails to respond adequately after 3 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, administration of Menotrophin is stopped. A single injection of 5,000 IU to 10,000 IU of hCG should be given 1 day after the last Menotrophin 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 Menotrophin is obtained, treatment should be stopped and hCG withheld (see section 4.4), and the patient should use a barrier method of contraception or refrain from having coitus until the next menstrual bleeding has started. Treatment should recommence in the next treatment cycle at a dose lower than in the previous cycle.

Women undergoing controlled ovarian hyperstimulation for multiple follicular development for assisted reproductive technologies (ART):

In a protocol using down-regulation with a GnRH agonist, Menotrophin therapy should start approximately 2 weeks after the start of agonist treatment. In a protocol using down-regulation with a GnRH antagonist, Menotrophin therapy should start on day 2 or 3 of the menstrual cycle. The recommended initial dose of Menotrophin 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 more than 150 IU per adjustment. The maximum daily dose given should not be higher than 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 injection of 5,000 IU up to 10,000 IU hCG 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 Menotrophin is obtained treatment should be stopped and hCG withheld (see section 4.4) and the patient should use a barrier method of contraception or refrain from having coitus until the next menstrual bleeding has started.

Male infertility:

Spermatogenesis is stimulated with chorionic gonadotrophin (1000 – 2000 IU two to three times a week) and then menotrophin is given in a dose of 75 or 150 IU units of FSH with 75 or 150 IU units of LH two or three times weekly. Treatment should be continued for at least 3 or 4 months.

Paediatric population:

There is no relevant use of Menotrophin in the paediatric population.

Elderly:

There is no relevant use of Menotrophin in the elderly population.

Method of Administration:

By intramuscular or subcutaneous use.

The powder must be reconstituted immediately with the solvent provided prior to use (see section 6.6). In order to avoid the injection of large volumes up to 3 vials of the powder may be dissolved in 1 ml of the solvent provided.

Shaking should be avoided. The solution should not be used if it contains particles or if it is not clear.

4.3 Contraindications

Women and Men

Menotrophin is contraindicated in women and men with:

– Tumours of the pituitary gland or hypothalamus

– Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

Women

– Ovarian, uterine or mammary carcinoma

– Pregnancy and lactation

– 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 Menotrophin should not be administered:

– Primary ovarian failure

– Malformation of sexual organs incompatible with pregnancy

– Fibroid tumours of the uterus incompatible with pregnancy

– Structural abnormalities in which a satisfactory outcome cannot be expected, for example, tubal occlusion (unless superovulation is to be induced for IVF), ovarian dysgenesis, absent uterus or premature menopause.

Men

– Tumours in the testes

– Prostate carcinoma

4.4 Special warnings and precautions for use

Menotrophin is a potent gonadotropic 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 inter-patient 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 first injection of Menotrophin 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, hyperprolactinemia 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 Menotrophin 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)

OHSS is a medical event distinct from uncomplicated ovarian enlargement. OHSS 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 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.

If urinary oestrogen levels exceed 540 nmol (150 micrograms)/24 hours, or if plasma 17 beta-oestradiol levels exceed 3000 pmol/L (800 picograms/ml), or if there is any steep rise in values, there is an increased risk of hyperstimulation and Menotrophin treatment should be immediately discontinued and human chorionic gonadotrophin withheld. Ultrasound will reveal any excessive follicular development and unintentional hyperstimulation.

The severe form OHSS may be life-threatening and is characterised by large ovarian cysts (prone to rupture), acute abdominal pain, ascites, very often hydrothorax and occasionally thromboembolic phenomena. Other symptoms that may be observed include: 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, haemoperitoneum, pleural effusions and acute pulmonary distress.

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. OHSS may progress rapidly (within 24 hours to several days) to become a serious medical event, therefore patients should be followed for at least two weeks after the hCG administration.

Adherence to recommended Menotrophin dosage, regimen of administration and careful monitoring of therapy will minimise the incidence of ovarian hyperstimulation and multiple pregnancy (see sections 4.2 and 4.8). Patients undergoing controlled ovarian hyperstimulation may be at an increased risk of developing hyperstimulation in view of the excessive oestrogen response and multiple follicular development. In ART, aspiration of all follicles prior to ovulation may reduce the occurrence of hyperstimulation.

OHSS 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 seven to ten 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 to 5%, as compared to 1 to 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 (e.g. maternal age, sperm characteristics) and multiple pregnancies.

Thromboembolic events

Women with generally recognised risk factors for thromboembolic events, such as personal or family history, severe obesity (Body Mass Index > 30kg/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.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed with Menotrophin in humans.

Although there is no controlled clinical experience, it is expected that the concomitant use of Menotrophin and clomiphene citrate may enhance the follicular response. When using GnRH agonist for pituitary desensitization, a higher dose of Menotrophin may be necessary to achieve adequate follicular response.

4.6 Fertility, pregnancy and lactation

Fertility

Menotrophin is indicated for use in infertility (see section 4.1).

Pregnancy

Menotrophin is contraindicated in women who are pregnant (see section 4.3).

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 Menotrophin during pregnancy (see section 5.3).

Breast-feeding

Menotrophin is contraindicated in women who are breast-feeding (see section 4.3).

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed. However, Menotrophin is unlikely to have influence on the patient’s ability to drive and use machines.

4.8 Undesirable effects

The most frequently reported adverse drug reactions (ADR) during treatment with Menotrophin in clinical trials are Ovarian Hyperstimulation Syndrome OHSS, abdominal pain, headache, abdominal distension, and injection site pain. None of these ADRs have been reported with an incidence rate of more than 5%.

The table below displays the main ADR in women treated with Menotrophin in clinical trials distributed by system organ classes (SOCs) and frequency. ADRs seen during post-marketing experience are mentioned with unknown frequency.

^a Most frequently reported injection site reaction was injection site pain.

^b Cases of localised or generalised allergic reactions , including anaphylactic reaction, along with associated symptomatology have been reported rarely.

^c Musculoskeletal pain includes arthralgia, back pain, neck pain and pain in extremities.

^d Gastrointestinal symptoms associated with OHSS such as abdominal distension and discomfort, nausea, vomiting, diarrhoea have been reported with Menotrophin in clinical trials. In cases of severe OHSS ascites and pelvic fluid collection, pleural effusion, dyspnoea, oliguria, thromboembolic events and ovarian torsion have been reported as rare complications.

^e Pelvic pain includes ovarian pain and adnexa uteri pain.

^f Breast complaints include breast pain, breast tenderness, breast discomfort, nipple pain and breast 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.

4.9 Overdose

The effects of an overdose is unknown, nevertheless one could expect ovarian hyperstimulation syndrome to occur (see section 4.4).

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Gonadotrophins

Menotrophin (Human Menopausal Gonadotrophin, HMG ) is a gonadotrophin extracted from the urine of postmenopausal women. It has both luteinising hormone and follicle stimulating hormone activity in a 1:1 ratio. Human Chorionic Gonadotrophin (hCG), a naturally occurring hormone in postmenopausal urine, is present in Menotrophin and is the main contributor of the LH activity.

Menotrophin (HMG) directly affects the ovaries and the testes. HMG has a gametropic and steroidogenic effect.

In the ovaries, the FSH-component in HMG induces an increase in the number of growing follicles and stimulates their development. FSH increases the production of oestradiol in the granulosa cells by aromatising androgens that originate in the Theca cells under the influence of the LH-component.

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 steroidogenesis, oestradiol levels associated with treatment with Menotrophin are higher than with recombinant FSH preparations in downregulated IVF/ICSI cycles. This issue should be considered when monitoring patient’s response based on oestradiol levels.

In the testes, FSH induces the transformation of premature to mature Sertoli cells. It mainly causes the maturation of the seminal canals and the development of the spermatozoa. However, a high concentration of androgens within the testes is necessary and can be attained by a prior treatment using hCG.

5.2 Pharmacokinetic properties

The pharmacokinetics of menotrophin following intramuscular or subcutaneous administration shows great interindividual variability. After 7 days of repeated dosing with 150 IU Menotrophin in downregulated healthy female volunteers, plasma FSH concentrations Cmax (baseline-corrected) (mean ± SD) were 8.9 ± 3.5 IU/L and 8.4 ± 3.2 IU/L for the SC and IM administration, respectively. The area under the curve (AUC) of FSH concentration was (mean ± SD) 180 ± 77 h.IU/L and 166 ± 67 h.IU/L for SC and IM administration, respectively. Maximum FSH concentrations were reached (Tmax) within 7 hours for both routes of administration. After repeated administration, FSH was eliminated with a half-life (T1/2) (mean ± SD) of 30 ± 11 hours and 27 ± 9 hours 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 Menotrophin, the data available were too sparse to be subjected to a pharmacokinetic analysis.

Menotrophin is excreted primarily via the kidneys.

The pharmacokinetics of Menotrophin in patients with renal or hepatic impairment has not been investigated.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans, which is not known from the extensive clinical experience.

Reproduction toxicity studies have not been carried out to evaluate the effects of Menotrophin during pregnancy or post-partum as Menotrophin is not indicated during these periods.

Menotrophin consist of naturally occurring hormones and should be expected to be non-genotoxic.

Carcinogenicity studies have not been carried out as the indication is for short term treatment.

6. Pharmaceutical particulars

6.1 List of excipients

Powder:

Lactose,Polysorbate 20, Sodium hydroxide

Hydrochloric acid (for pH adjustment)

Solvent:

Sodium chloride,, Hydrochloric acid (for pH adjustment),, Water for injections

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

Two years as packaged for sale.

The reconstituted product should be used immediately, and any remaining solution should be discarded.

For immediate and single use following reconstitution.

6.4 Special precautions for storage

Do not store above 25°C. Do not freeze. Store in the original container to protect from light.

6.5 Nature and contents of container

Menotrophin is available in the following containers and pack sizes:

Powder: 2 ml colourless glass (Type I) vial with rubber stopper closed with a cap.

Solvent: 1 ml colourless glass (Type I) ampoule.

The product is supplied in packs of 1, 5 or 10 vials with the corresponding number of solvent ampoules.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

The powder should only be reconstituted with the solvent provided in the package.

Attach the reconstitution needle to the syringe. Withdraw the entire content from the ampoule with solvent and inject the total contents into the vial containing the powder. 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.

If needed, the solution can be drawn up into the syringe again to transfer it to the next vial with powder until the prescribed dose has been reached. Up to three powder vials can be dissolved with one ampoule of solvent.

When the prescribed dose has been reached, draw up the mixed solution from the vial into the syringe, change to the hypodermic needle and administer immediately.

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.

7. Manufactured in India by:
   TAJ PHARMACEUTICALS LTD.
   Mumbai, India
   Unit No. 214.Old Bake House,
   Maharashtra chambers of Commerce Lane,
   Fort, Mumbai – 400001
   at:Gujarat, INDIA.
   Customer Service and Product Inquiries:
   1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
   Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
   E-mail: tajgroup@tajpharma.com

Menotrophin for Injection 75 IU, 150 IU BP

PACKAGE LEAFLET: INFORMATION FOR THE USER 

Highly purified menotrophin

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it
• If you have any further questions, ask your doctor, nurse or pharmacist.
• This medicine has been prescribed for Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you get any side effects, talk to your doctor, nurse or pharmacist. This includes any possible side effects not listed in this leaflet. See section

What is in this leaflet:

1. What Menotrophin is and what it is used for
2. What you need to know before you use Menotrophin
3. How to use Menotrophin
4. Possible side effects
5. How to store Menotrophin
6. Content of the pack and other information

1.   What Menotrophin is and what it is used for

Menotrophin is provided as a powder which must be mixed with liquid (solvent) before it is used. It is given as an injection into a muscle or under the skin.

What Menotrophin is

Menotrophin contains the active substance menotrophin which belongs to a group of medicines called gonadotrophins.

Menotrophin is a highly purified mixture of two hormones called follicle stimulating hormone (FSH) and luteinizing hormone (LH). FSH and LH are natural hormones produced in both males and females. They help the reproductive organs to work normally.

The FSH and LH in menopur are obtained from the urine of postmenopausal women.

What Menotrophin is used for

In women, Menotrophin is used to treat infertility in the following two situations:

• To promote the release of eggs from the ovaries (ovulation) in women who are not ovulating including with polycystic ovarian disease and who have not responded to treatment with another medicine called clomiphene
• To help multiple follicles and therefore eggs to develop in women having in vitro fertilisation (IVF) treatment or other types of ‘assisted conception’. The eggs are then harvested and fertilised outside the

In men, Menotrophin is used to treat infertility in the following situation:

• Low sperm count (oligospermia).

2.What you need to know before you use Menotrophin

Before starting treatment with Menotrophin, you and your partner should be evaluated by a doctor for the causes of your fertility problems. In particular you should be checked for the following conditions so that any other appropriate treatment can be given:

• Underactive thyroid or adrenal glands
• High levels of a hormone called prolactin (hyperprolactinemia)
• Tumours of the pituitary gland (a gland located on the base of the brain which produces certain hormones, including growth hormones)
• Tumours of the hypothalamus (an area located under the part of the brain called the thalamus which controls the conditions within your body including body temperature and blood pressure)

If you know you have any of the conditions listed above, please tell your doctor before starting treatment with Menotrophin.

Do not use Menotrophin if:

• You are allergic (hypersensitive) to menotrophin or any of the other ingredients of Menotrophin (listed in Section 6).
• You have a tumour in your pituitary
• You have a tumour in the

Also, if you are a woman do not use Menotrophin if:

• You have tumours of the womb (uterus), ovaries or
• You have sacs of fluid known as cysts on your ovaries (ovarian cysts) or enlarged ovaries that are not due to polycystic ovarian disease (a condition that prevents eggs from being released from the ovaries).
• You have bleeding from your vagina for an unknown reason.
• You are having an early (premature)
• You have certain physical problems in your reproductive organs (womb, fallopian tubes, ovaries or cervix).
• Your womb has been removed (hysterectomy).
• You have fibroid tumours (tumours in your womb that are not cancer).
• You are pregnant or breast-feeding.

Also, if you are a man do not use Menotrophin if:

• You have cancer of your
• You have prostate

Do not use Menotrophin if any of the above applies to you. If you are not sure, talk to your doctor, nurse or pharmacist before you start using Menotrophin.

Warnings and precautions

Talk to your doctor or nurse if:

• You get pain or swelling in the stomach
• You get nausea or vomiting
• You get diarrhea
• You gain weight
• You have difficulty in breathing
• You get decreased urination (produce less urine)

Tell your doctor straight away, even if the symptoms develop some days after the last injection has been given. These can be signs of high levels of activity in the ovaries which might become severe.

If these symptoms become severe, the infertility treatment should be stopped and you should receive treatment in hospital.

Keeping to your recommended dose and careful monitoring of your treatment will reduce your chances of getting these symptoms.

If you stop using Menotrophin you might still experience these symptoms. Please contact your doctor immediately if any of these symptoms occur.

While you are being treated with this medicine, your doctor  will normally arrange for you to have ultrasound scans and sometimes blood tests to monitor your response to treatment.

Being treated with hormones like Menotrophin can increase the risk of:

• Ectopic pregnancy (pregnancy outside of the womb) if you have a history of fallopian tube
• Miscarriage
• Multiple pregnancy (twins, triplets, etc)
• Congenital malformations (physical defects present in baby at birth).

Some women who have been given infertility treatment with multiple medicines have developed tumours in the ovaries and other reproductive organs. It is not yet known if treatment with hormones like Menotrophin causes these problems.

Blood clot formation inside the blood vessels (veins or arteries) are more likely to occur in women who are pregnant. Infertility treatment can increase the chances of this happening, especially if you are overweight or known with blood clotting disease (thrombophilia) or if you or someone in your family (blood relative) has had blood clots. Tell your doctor if you think this applies to you.

Children

There is no relevent use of Menotrophin in children.

Other medicines and Menotrophin

Tell your doctor if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.

Clomiphene citrate is another medicine used in the treatment of infertility. If Menotrophin is used at the same time as clomiphene citrate the effect on the ovaries may be increased.

Pregnancy and breast-feeding

Menotrophin should not be used during pregnancy or breast- feeding.

Driving and using machines

Menotrophin is unlikely to affect your ability to drive and use machines.

Important information about some of the ingredients of Menotrophin

Menotrophin contains less than 1 mmol sodium (23 mg) per dose, so it is essentially ‘sodium-free’. Menotrophin also contains lactose (which is a type of sugar). If you have been told by your doctor that you cannot tolerate or digest some sugars (have an intolerance to some sugars), talk to your doctor before using this medicine.

3.  How to use Menotrophin

Always use Menotrophin exactly as your doctor or nurse has told you. You should check with your doctor, nurse or pharmacist if you are not sure.

Using Menotrophin

• You will have Menotrophin as an injection into a muscle or under the
• You will either be given Menotrophin by a doctor or nurse or you will be taught how to give it to
• Menotrophin comes as a dry powder in small bottles (vials).
• Once the dry powder has been mixed with the salt solution (solvent) it should be used straight

The dose and length of your treatment

• The dose, and how long your treatment lasts, depends on why you are using Menotrophin and how well it
• Your doctor or nurse will monitor how you respond to your treatment.
• This will help them to work out what dose you need and how long you need to use Menotrophin

In women:

• Women who are not ovulating (not producing eggs):

Treatment should start within the first 7 days of the menstrual cycle (day 1 is the first day of your period). Treatment should be given every day for at least 7 days.

The starting dose is normally 75-150 IU daily but this may be adjusted depending on your response (up to a maximum of 225 IU). A particular dose should be given for at least 7 days before the dose is changed by your doctor. It is recommended that the dose should be increased by 37.5 IU per adjustment (and not more than 75 IU). The cycle of treatment should be abandoned if there is no response after 3 weeks.

When a good response is obtained a single injection of another hormone called human chorionic gonadotrophin (hCG), at a dose of 5,000 to 10,000 IU, should be given 1 day following  the last Menotrophin injection. It is recommended to have sexual intercourse on the day of the hCG injection and the day after. Alternatively, artificial insemination (injection of sperm directly into the womb) may be performed. Your doctor will closely monitor your progress for at least 2 weeks after you have received the hCG injection.

Your doctor will monitor the effect of Menotrophin treatment. If an excessive response occurs, your doctor may decide to stop treatment with Menotrophin and not give you the hCG injection. In this case, you will be instructed to use a barrier method of contraception (e.g. condom) or not have sexual intercourse until your next period has started. For the following cycle your doctor will give you a lower dose of Menotrophin than before.

ii   Women in assisted reproductive technology programs:

If you are also receiving treatment with a GnRH agonist (a medicine which helps a hormone called Gonadotropin Releasing Hormone (GnRH) to work), Menotrophin should be started approximately 2 weeks after the start of the GnRH agonist therapy.

If you are also receiving treatment with a GnRH antagonist, Menotrophin treatment should be started on day 2 or 3 of the menstrual cycle (day 1 is the first day of your period).

Menotrophin should be given every day for at least 5 days. The initial dose of Menotrophin is normally 150-225 IU. This dose may be increased according to your response to the treatment up to  a maximum of 450 IU per day. The dose should not be increased by more than 150 IU per adjustment. Normally treatment should not continue for more than 20 days.

If enough egg sacs are present, you will be given a single injection of a medicine called human chorionic gonadotrophin (hCG) at a dose of up to 10,000 IU to induce ovulation (release of an egg).

Your doctor will closely monitor your progress for at least 2 weeks after you have received the hCG injection.

Your doctor will monitor the effect of Menotrophin treatment. If an excessive response occurs, your doctor may decide to stop treatment with Menotrophin and not give you the hCG injection. In this case, you will be instructed to use a barrier method of contraception (e.g. condom) or not have sexual intercourse until your next period has started. For the following cycle your doctor will give you a lower dose of Menotrophin than before.

In men:

For low sperm count:

• The usual dose is 75 or 150 IU two or three times a
• Treatment is normally continued for at least 3 or 4

INSTRUCTIONS FOR USE

If your doctor has asked you to inject Menotrophin yourself, you should follow the instructions provided below.

The first injection of Menotrophin should be given under the supervision of a doctor or nurse.

If you use more Menotrophin than you should

If you think you have used too much Menotrophin, tell your doctor, nurse or pharmacist.

If you forget to use Menotrophin

Do not take a double dose to make up for a forgotten dose. Please tell your doctor, nurse or pharmacist.

4.   Possible side effects

Like all medicines, Menotrophin can cause side effects, although not everybody gets them.

Side effects that can happen in women:

If you notice any of the following signs, tell your doctor immediately. It may mean that your ovaries have been stimulated too much Ovarian Hyperstimulation Syndrome  (OHSS), especially in women with polycystic ovaries and you may need urgent medical treatment.

Symptoms include:

• Nausea (feeling sick)
• Vomiting (being sick)
• Weight
• Pain or swelling of the stomach

In cases of severe OHSS:

• Fluid build-up in the stomach, pelvis and/or chest
• Difficulty in
• Decreased urination (producing less urine when you go to the toilet or going to the toilet less often).
• Formation of blood clots in blood vessels (thromboembolism)
• Twisting of ovaries (ovarian torsion)

If you notice any of the above signs, tell your doctor immediately.

Side effects that can happen in both women and men: STOP USING Menotrophin if you experience allergic (hypersensitivity) reactions including; skin rashes, itching, swelling of the face, lips or throat and difficulty in breathing.

If you experience any of these rare side effects, you should contact your doctor or go to the nearest hospital immediately.

Common (may affect up to 1 in 10 people):

• Pain or swelling of the stomach
• Headache
• Nausea
• Pelvic pain
• Overstimulation of the ovaries resulting into high levels of activity (OHSS)
• Pain or inflammation at the injection site (redness, bruising, swelling and/or itching)

Uncommon (may affect up to 1 in 100 people):

• Vomiting
• Discomfort in stomach
• Diarrhoea
• Fatigue
• Dizziness
• Sacs of fluid within ovaries (ovarian cysts)
• Breast complaints (include breast pain, breast tenderness, breast discomfort, nipple pain and breast swelling)
• Hot flush

Rare (may affect up to 1 in 1,000 people)

• Acne
• Rash

Unknown (the frequency of these reported side effects is not known)

• Eyesight disturbances
• Allergic reactions
• Pain in muscle and joint (e.g. back pain, neck pain and pain in arms and legs)
• Twisting of ovary (ovarian torsion) as a complication of OHSS
• Itching
• Hives

Reporting of side effects

If you get any side effects, talk to your doctor, nurse or pharmacist. This includes any possible side effects not listed     in this leaflet.

5.   How to store Menotrophin

• Keep out of the sight and reach of
• Do not use Menotrophin after the expiry date which is stated on the The expiry date refers to the last day of that month.
• For immediate and single use following
• Do not store above 25°C. Do not
• Store in the original package in order to protect from
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the

6.   Content of the pack and other information

What Menotrophin contains

• Menotrophin is a sterile freeze dried powder for injection. The active substance is Highly Purified Menotrophin. Each vial contains 75 IU of the active substance, corresponding to 75IU of FSH activitiy and 75IU of LH
• The other ingredients for powder are Lactose monohydrate, Polysorbate 20, Sodium hydroxide and Hydrochloric
• The solvent (Sodium Chloride Solution for Injections 0.9% w/v) contains, Sodium chloride, Hydrochloric acid and Water for

What Menotrophin looks like and contents of the pack

Menotrophin is powder and solvent for solution for injection. Supplied in cartons of 1, 5 or 10 clear glass vials which contain   a white to off-white lyophilised powder.

The carton also contains an equal number of clear glass ampoules containing a colourless solvent (Sodium Chloride Solution for Injection 0.9%w/v). The solvent is used to dissolve the powder before it is injected.

Not all pack sizes may be marketed.

7.Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com