HuMog

Before Reconstitution: A white powder or cake.
After Reconstitution: Clear colourless solution.
Solvent Sodium Chloride Injection: A clear and colourless solution.
Each vial contains: Menotrophin B.P. equivalent to activity of Follicle Stimulating Hormone 75 I.U./150 I.U., Luteinizing Hormone 75 I.U./150 I.U.
One I.U. of human urinary FSH and one I.U. of human urinary LH are defined as the activities contained in 0.11388 mg and 0.13369 mg of the 1st International Standard respectively.
Each vial of HuMoG is accompanied by an ampoule of Sodium Chloride Injection BP 1 mL as solvent.
Excipients/Inactive Ingredients: Mannitol BP, Sucrose BP, Sodium Ascorbate BP, Anhydrous Di-Sodium Hydrogen Phosphate BP and Phosphoric Acid BP.

ATC Code: G03GA02-Human Menopausal Gonadotropin.
Pharmacology: Pharmacodynamics: HuMoG (Human Menopausal Gonadotropin) is a hormonal substance containing FSH and LH in ration of 1:1.
In females, HuMoG stimulates both the growth and maturation of follicles. It induces an increase in the oestrogen levels and proliferation of the endometrium.
In males, HuMoG stimulates the spermatogenesis by acting on the production of the androgen-binding protein in the seminiferous tubules of the sertoli cells.
Pharmacokinetics: Human menopausal gonadotrophins (HMG) is not effective when taken orally and is injected intra-muscularly. The HMG biological effectiveness is mainly due to its FSH content. The pharmacokinetics of HMG following IM administration shows great individual variations. The maximum serum level of FSH is reached 6-24 hours after injection, resp. 6-36 hours after SC injection. After that the serum level decreases by a half-life of 56 (IM) resp.51 (SC) hours.
Administered HMG is predominantly discharged renally.

Women: Sterility in females with hypo- or normogonadotrophic ovarian insufficiency: Stimulation of follicle growth.
Men: Sterility in males with hypo- or normogonadotrophic hypogonadism: In combination with HCG to stimulate spermatogenesis.

Unless prescribed otherwise, dose as follows: Sterility in females: The dosage of HMG for the induction of follicle growth in normo- or hypogonadotrophic women varies according to the individual. The amount depends on ovarian reaction and should be checked by ultrasound examinations of the ovaries and measuring estradiol levels. If the HMG dosage is too high for the treated individual, multiple uni- and bilateral follicle growth can occur.
HMG is administered intramuscularly or subcutaneously and in general, the therapy is begun with a daily dosage corresponding to 75-150 IU FSH. If the ovaries do not respond, the dosage can slowly be increased until a rise in estradiol secretion and follicle growth is evident. Treatment with the same dosage of HMG continues until the preovulatory estradiol serum level is attained. If the level rises too quickly, the dosage should be reduced. To induce ovulation, 5,000 or 10,000 IU HCG are injected IM 1 to 2 days after the last HMG administration.
Note: After administering a HMG dosage which is too high for the corresponding individual, a subsequent HCG administration can cause an unintentional hyperstimulation of the ovaries.
Sterility in males: Initially, 3 x 1,000 and 3,000 IU HCG a week are administered until a normal testosterone serum level is reached. Then, an additional dose of HMG (3 x 75-150 IU FSH + 75-150 IU LH) per week is administered IM for a few months. Treatment should be continued for at least 3 or 4 months.
Reconstitution Instructions: Reconstitute powder of vial in 1ml of Sodium Chloride Injection BP provided in the pack immediately prior to use. Up to 5 vials of HuMoG may be reconstituted in 1ml of Sodium Chloride Injection BP.
Route of Administration: Intramuscular (IM) + Subcutaneous (SC).

The acute toxicity of menotrophin has been shown to be very low. However, too high a dosage for more than one day may lead to hyperstimulation, which is categorised as mild, moderate or severe. Symptoms of overdosage usually appear 3-6 days after treatment with human chorionic gonadotrophin.
Mild hyperstimulation: Symptoms include some abdominal swelling and pain; ovaries enlarged to about 5 cm diameter. Therapy: rest; careful observation and symptomatic relief. Ovarian enlargement declines rapidly.
Moderate hyperstimulation: Symptoms include more pronounced abdominal distension and pain; nausea; vomiting; occasional diarrhoea; ovaries enlarged up to 12 cm diameter. Therapy: bed rest; close observation especially in the case of conception occurring, to detect any progression to severe hyperstimulation. Pelvic examination of enlarged ovaries should be gentle in order to avoid rupture of the cysts. Symptoms subside spontaneously over 2-3 weeks.
Severe hyperstimulation: This is a rare but serious complication, symptoms include pronounced abdominal distension and pain; ascites; pleural effusion; decreased blood volume; reduced urine output; electrolyte imbalance and sometimes shock; ovaries enlarge to in excess of 12 cm diameter. Therapy: hospitalisation; treatment should be conservative and concentrate on restoring blood volume and preventing shock. Acute symptoms subside over several days and ovaries return to normal over 20-40 days if conception does not occur, symptoms may be prolonged if conception occurs.

In females: Pregnancy; Enlargement of the ovaries or cysts that is not caused by polycystic ovarian syndrome; Gynaecological bleeding of unknown cause; Tumours in the uterus, ovaries and breasts.
In males: Carcinoma of the prostate; Tumours in the testes.
The following conditions should be properly treated before HMG-therapy is begun: dysfunction of the thyroid gland and of the cortex of the suprarenal gland, a rise in the serum level of prolactin with different causes (hyperprolactinaemia), tumours in the pituitary gland (hypophysis) or in part of the diencephalons (hypothalamus).

The following conditions should be properly treated and excluded as the cause of infertility before menotrophin therapy is initiated: Dysfunction of the thyroid gland and cortex of the suprarenal gland; Hyperprolactinaemia; Tumours in the pituitary or hypothalamic glands.
In the treatment of female infertility, ovarian activity should be checked (by ultrasound and plasma 17 beta-oestradiol measurement) prior to HuMoG administration. During treatment, these tests and urinary oestrogen measurement should be carried out at regular intervals, until stimulation occurs. Close supervision is imperative during treatment. See Dosage & Administration for optimum response levels of urinary oestrogens and plasma 17 beta-oestradiol.
Values below these ranges may indicate inadequate follicular development. If urinary oestrogen levels exceed 540 nmol (150 micrograms)/24 hours, or if plasma 17 beta-oestradiol levels exceed 3,000 pmol/L (800 picograms/ml), or if there is any steep rise in values, there is an increased risk of hyperstimulation and HuMoG treatment should be immediately discontinued, and human chorionic gonadotrophin withheld. Ultrasound will reveal any excessive follicular development and unintentional hyperstimulation. In the event of hyperstimulation, the patient should refrain from sexual intercourse until they are no longer at risk.
If during ultrasound, several mature follicles are visualised, human chorionic gonadotrophin should not be given as there is a risk of multiple ovulation and the occurrence of hyperstimulation syndrome.
Patients undergoing superovulation may be at an increased risk of developing hyperstimulation in view of the excessive oestrogen response and multiple follicular development. Aspiration of all follicles, prior to ovulation, may reduce the incidence of hyperstimulation syndrome.
The severe form of hyperstimulation syndrome 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.
Prior to treatment with HuMoG, primary ovarian failure should be excluded by the determination of gonadotrophin levels.
There have been reports of ectopic pregnancy in women receiving menotrophin who have undergone assisted conception. One predisposing factor for ectopic pregnancy is tubal disease/occlusion, which women undergoing assisted conception may have. No causal relationship between ectopic pregnancy and the use of menotrophin has been established.
Special precautions for the physician: HCG should not be administered to induce ovulation in females whose ovaries have unintentionally been hyperstimulated.
When treating sterile women, ovarian activity should be checked (ultrasound and estradiol levels in serum resp.) prior to HMG administration. During treatment, these tests should be carried out every one to two days until stimulation occurs. Ovarian reaction can also be measured using a cervix index.
Close supervision is imperative during treatment. Treatment should be immediately discontinued if unintentional hyperstimulation occurs.
Effects on ability to drive and use machine: No studies on the effects on the ability to drive and use machines have been performed. However, HuMoG is unlikely to have influence on the patient's ability to drive and use machines.

HuMoG should not be given if pregnancy is suspected or to lactating mothers.

In the female, a local reaction at the injection site, fever and arthralgia have been observed in rare cases. In the male, a combined treatment with HuMoG and HuCoG may cause gynecomastia.
Occasionally, nausea and vomiting can occur.
In single cases, hypersensitivity reactions and fever can occur during treatment with HuMoG. The administration of HuMoG may lead to reactions at the injection site: reddening, pain, swelling and itching. In very rare cases, long-term usage can lead to the formation of anti-bodies, making the therapy ineffective.
Treatment with HuMoG can often lead to ovarian hyperstimulation that first becomes clinically relevant after the administration of HuCoG (pregnancy hormone) to induce ovulation. This can lead to the formation of large ovarian cysts that tend to rupture, and to intraabdominal bleeding. In addition, the accumulation of fluids in the abdominal cavity (ascites), the accumulation of fluids in the chest cavity (hydrothorax), a decrease in the excretion of urine (oliguria), lowering of the blood pressure (hypotension), and occlusion of blood vessels by blood clots (thromboembolic phenomena) can occur.
Treatment should be immediately discontinued when the first signs of hyperstimulation appear: abdominal pain and a palpable (by the physician) enlargement in the lower abdomen, which can be detected sonographically.
If abdominal pain occurs, see a physician.
If pregnancy occurs, these side effects can intensify, continues over a long period of time, and be life-threatening.
Unintentional multiple pregnancies occur more often during treatment with HuMoG.

Interactions with other medications are unknown. HMG can be injected together with HCG when treating infertile males.
Incompatibilities: No drug incompatibilities has been reported so far. It should not be mixed with other drugs in the same ampoule or syringe.

Vials of HuMoG with 1ml Sodium Chloride Injection BP as solvent should be stored between 2°C-8°C. Do not freeze. Protect from light.
Reconstituted solution of HuMoG should be used immediately after preparation. Discard any unused portion.
Shelf Life: HuMoG: 36 months.
Solvent Sodium Chloride Injection: 60 months.

Trophic Hormones & Related Synthetic Drugs

G03GA02 - human menopausal gonadotrophin ; Belongs to the class of gonadotropins. Used as ovulation stimulants.

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