PDpreg

Package and drug specifications

• Vial: Including 5000 IU of human chorionic gonadotropin lyophilized powder

• Solvent ampoule: Including 1 mL of Sodium chloride 0.9%

• Medical staff and patients guide

Qualitative composition

• Vial: Lyophilized, sterile and white powder

• Solvent ampoule: Sterile, colorless and free of any visible particles

Tips to be advised to the patient

• Effects on the ability to drive and use machines: PDpreg^® has no effect on the ability to drive and use machines.

• Tell your doctor or pharmacist if you have any side effects.

• If you accidentally use more than the recommended amount, visit your doctor or healthcare provider immediately.

• If you have missed an injection, or injected too little, contact your doctor as soon as possible. Do not take a double dose to make up for any missed doses.

• This medicine is prescribed for your current condition. So do not use it in similar cases or advice to others.

• It is recommended that when using this drug, the name and serial number of the product is recorded in order to maintain the records of the manufacturing series used.

• The prepared solution can only be used once after preparation. Discard the remainder of the medicine after taking.

Use:

Therapeutic indications

• Hypogonadotropic hypogonadism

Treatment of hypogonadism secondary to a pituitary deficiency in males

• Ovulation induction

Induction of ovulation and pregnancy in the anovulatory, infertile woman in whom the cause of anovulation is secondary and not caused by primary ovarian failure, and who has been appropriately pretreated with human menotropins

• Prepubertal cryptorchidism

Treatment of prepubertal cryptorchidism not caused by anatomic obstruction

Contraindications

• Hypersensitivity to chorionic gonadotropin or any component of the formulation

• The presence of sex hormones-related tumors such as ovarian, uterine or breast carcinoma in women and prostate and breast carcinoma in men

• Malformations of the sexual organs incompatible with pregnancy

• Fibroid tumors of the uterus incompatible with pregnancy

• Vaginal bleeding due to unspecified cause

Warning and precautions

• Hypersensitivity reactions

Hypersensitivity reactions, both generalized and local; anaphylaxis; and angioedema have been reported. If a hypersensitivity reaction is suspected, discontinue PDpreg^®.

• Thromboembolism

Arterial and venous thromboembolism, both in association with and separate from OHSS have been reported following treatment with gonadotropins. Women with generally recognized risk factors for thrombosis, such as a personal or family history, severe obesity or thrombophilia, may have an increased risk of venous or arterial thromboembolic events, during or following treatment with gonadotropins. It should be noted, however, that pregnancy itself also carries an increased risk of thrombosis.

• Asthma

Use with caution in patients with asthma.

• Cardiovascular disease

Use with caution in patients with cardiovascular disease.

• Migraine

Use with caution in patients with a history of migraines.

• Seizure disorders

Use with caution in patients with a history of seizure disorders.

• Male pediatric patients

PDpreg^® may induce precocious puberty in children being treated for cryptorchidism; discontinue if signs of precocious puberty occur. PDpreg^® should be used cautiously in prepubertal boys to avoid premature epiphyseal closure or precocious sexual development. Skeletal maturation should be monitored regularly.

• Obesity

PDpreg^® is not effective adjunctive therapy in the treatment of obesity. (Fat metabolism, fat distribution or appetite)

• Ovarian Hyperstimulation Syndrome (OHSS)

OHSS is a medical event distinct from uncomplicated ovarian enlargement. Clinical signs and symptoms of mild and moderate OHSS are abdominal pain, nausea, diarrhea, mild to moderate enlargement of ovaries and ovarian cysts. Severe OHSS may be life-threatening. Clinical signs and symptoms of severe OHSS are large ovarian cysts, acute abdominal pain, ascites, pleural effusion, hydrothorax, dyspnea, oliguria, hematological abnormalities and weight gain. In rare instances, venous or arterial thromboembolism may occur in association with OHSS. Transient liver function test abnormalities suggestive of hepatic dysfunction with or without morphologic changes on liver biopsy have also been reported in association with OHSS. OHSS may be caused by administration of human Chorionic Gonadotropin (hCG) and by pregnancy (endogenous hCG). Early OHSS usually occurs within 10 days after PDpreg^® administration and may be associated with an excessive ovarian response to gonadotropin stimulation. Late OHSS occurs more than 10 days after PDpreg^® administration, as a consequence of the hormonal changes with pregnancy. Because of the risk of developing OHSS, patients should be monitored for at least two weeks after PDpreg^® administration. Women with known risk factors for a high ovarian response may be especially prone to the development of OHSS during or following treatment with PDpreg^®. For women having their first cycle of ovarian stimulation, for which risk factors are only partially known, close observation for early signs and symptoms of OHSS is recommended. To reduce the risk of OHSS, ultrasonographic assessments of follicular development should be performed prior to treatment and at regular intervals during treatment. The concurrent determination of serum estradiol levels may also be useful. In ART, there is an increased risk of OHSS with 18 or more follicles of 11 mm or more in diameter. When there are 30 or more follicles in total, it is advised to withhold PDpreg^® administration.

• Multi-fetal gestation and birth

In the pregnancies occurring after induction of ovulation with gonadotropic preparations, there is an increased risk of abortion and multiplets. Multiple pregnancies, especially high order, carry an increased risk in adverse maternal and perinatal outcomes. The parents should be advised of the potential risks of multiple pregnancies before starting treatment.

• Ectopic pregnancy

Infertile women undergoing Assisted Reproductive Technologies (ART) have an increased incidence of ectopic pregnancy. Early ultrasound confirmation that a pregnancy is intrauterine is therefore important. Prior to treating patients for inadequate endogenous stimulation of the gonads, an examination should be performed to exclude anatomical abnormalities of the genital organs or nongonadal endocrinopathies (e.g. thyroid or adrenal disorders, diabetes). Primary ovarian failure should be excluded by the determination of gonadotropin levels.

• Congenital Malformations

The incidence of congenital malformations after Assisted Reproductive Technologies (ART) may be higher than after spontaneous conceptions. This is thought to be due to differences in parental characteristics (e.g. maternal age, sperm characteristics) and an increased incidence of multiple gestations.

• Ovarian torsion

Ovarian torsion has been reported after treatment with gonadotropins, including PDpreg^®. Ovarian torsion may be related to other conditions, such as OHSS, pregnancy, previous abdominal surgery, past history of ovarian torsion, and previous or current ovarian cysts. Damage to the ovary due to reduced blood supply can be limited by early diagnosis and immediate detorsion.

• Medical examinations

For up to ten days after administration of PDpreg^®, a pregnancy test may give a false-positive result.

• Antibody formation

Administration of PDpreg^® can provoke the formation of antibodies against hCG. In rare cases, this may result in an ineffective treatment.

Use in pregnancy

The pregnancy category of this drug is X and it is prohibited to use it during pregnancy.

Use in lactation

There is not enough information available on the secretion of PDpreg^® in breast milk. However, if the benefits of taking medication are of primary importance to the mother, prescribing the medication is done with caution, according to the physician’s decision.

Dosing and method of administration

• Ovulation induction

5000 – 10000 units 1 day following last dose of menotropins

• Hypogonadotropic hypogonadism

• Regimen 1: 500 – 1000 units 3 times/week for 3 weeks, followed by the same dose twice weekly for 3 weeks

• Regimen 2: 4000 units 3 times/week for 6 to 9 months, then reduce dosage to 2000 units 3 times/week for additional 3 months

• Prepubertal cryptorchidism

• Regimen 1: 4000 units 3 times weekly for 3 weeks

• Regimen 2: 5000 units every second day for 4 injections

• Regimen 3: 500 units 3 times weekly for 4 to 6 weeks (if not successful may repeat course one month later using 1000 units/dose)

• Regimen 4: 15 injections of 500 – 1000 units administered over 6 weeks

• Use in renal impairment

Given the fact that androgens cause fluid retention, be used with caution.

• Hepatic impairment

The use of this drug in liver failure does not require dose adjustment.

Preparation and administration

• Injection of this drug is intramuscularly (recommended and preferred) and subcutaneous injection.

• Do not use the drug in the event of cracking or any damage to the vials and ampoules.

• Using the method described by your doctor or pharmacist, first disinfect the vial with alcohol and add the solvent injection into the vial containing the medicine slowly with a syringe. Then rotate the vial slowly and with rotational movements (during preparation, avoid vigorous vibration) to completely dissolve the contents of the powder. The resulting solution should be clear and free of any particles. Otherwise, do not take medication. Then, take the solution back into the syringe and take the intramuscularly or subcutaneously. Use the immediate solution immediately and keep the drug retained.

• Keep the medicine in the refrigerator at 2 to 8 ^°C and protect from frost.

• Keep the medicine away from light and in the original package.

• Avoid placing the drug in the vicinity of direct sunlight or using any heat source such as hot water to deliver the medicine to the ambient temperature.

• Keep the medicine out of the reach and sight of children.

• Avoid taking an expired medicine. The expiry date is shown on the original packaging and vial label. The expiration date is the last day of the month.

• The prepared solution is clear, colorless and free of particles, if you notice any change in color or particle, do not use it.

• This product is one-time use. Discard the remainder of the medicine after taking.

Undesirable effects

“Any medication along with the therapeutic effects may also cause some unwanted side effects, although not all of these effects are seen in one person, consult your doctor or pharmacist if you have any of the following side effects.”

• The incidence of the following complications is unclear.

• Immune system disorders: Hypersensitivity reactions (Angioedema, Erythema, Rash, Fever, Urticaria, Dyspnea)

• General disorders and administrative site conditions: Bruising, Pain, Redness, Swelling and Itching, Edema

• Nervous system disorders: Headache, Fatigue, Irritability

• Psychiatric disorders: Mood changes, Depression

• Vascular disorders: Thromboembolism (especially in the treatment of chorionic gonadotropin and follicle-inducing hormone)

• Respiratory, thoracic and mediastinal: Hydrothorax

• Gastrointestinal disorders: Abdominal pain, Nausea, Diarrhea, Ascites

• Reproduction system and breast disorders: Ovarian hyperstimulation syndrome, Breast pain, Ovarian enlargement, Ovarian cyst and enlargement of cysts and rupture, Gynecomastia (enlargement of the breast), Precocious puberty

• Metabolism and nutrition disorders: Water and sodium retention is occasionally seen after administration of high dosages in men

• Skin and subcutaneous tissue disorders: Acne

• Investigational: Weight gain

Drug interactions

There are no known interactions.