Folligrowth

• Vial: Lyophilized, white to off-white sterile powder.

• Ampoule: Sterile, colorless and free of particles

• Powder: Mannitol, Disodium Hydrogen Phosphate, Sucrose, Phosphoric acid

• Solvent: Sodium chloride 0.9%

Tips to be advised to the patient

• Urofollitropin has no effect on consciousness. Therefore, there is no limit to the ability to work with machinery and driving.

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

• The effects of taking over the recommended amount of urofollitropin are unknown. However, it can cause excessive ovarian stimulation syndrome. If you take an extra dose randomly, contact your doctor or pharmacist for further advice.

• If you forget to take a dose of medicine, contact your doctor as soon as you remember and avoid double the dose.

• 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 used series.

• Urofollitropin can be used only once after preparation. Discard the remainder of the medicine after taking.

1. Long term treatment in pediatric patients showing growth retardation confirmed by inadequate secretion of the growth hormone.
2. Long term treatment in pediatric patients showing growth retardation confirmed by renal insufficiency.
3. Long term treatment in PWS pediatric patients.
4. Long term treatment in Turner syndrome pediatric patients.
5. Long term treatment in pediatric patients who were born smaller regarding their gestational age and who show growth retardation and lack of height recovery at two years of age.
6. Wasting syndrome in AIDS patients.
7. Replacement therapy in adults with pronounced growth hormone deficiency as diagnosed by a single dynamic test for growth hormone deficiency.
8. Idiopathic short stature.

Dosing and method of administration

• Ovulation induction

Adults: Females: IM, SubQ: Initial: 150 units once daily for 5 days in the first cycle of treatment. After 5 days, dose adjustments up to 75-150 units can be made every ≥2 days based on ultrasound monitoring of ovarian response and/or measurement of serum estradiol levels; maximum daily dose: 450 units; treatment >12 days is not recommended. If response to urofollitropin is appropriate, administer HCG; withhold the HCG dose if ovarian monitoring suggests an increased risk of OHSS and advise the patient to refrain from intercourse. For subsequent cycles, the starting dose and dosage adjustments should be determined based on historical ovarian response.

• Assisted reproductive technologies (ART)

Adults: Females: SubQ: Starting on day 2 or 3 of cycle, administer 225 units once daily for the first 5 days; urofollitropin may be administered together with menotropins and the total initial dose of both products combined should not exceed 225 units (menotropins 150 units and urofollitropin 75 units; or menotropins 75 units and urofollitropin 150 units). Adjust dose after 5 days based on ultrasound monitoring of ovarian response and measurement of serum estradiol levels. Do not make additional adjustments more frequently than once every 2 days or by >75-150 units. Maximum daily dose: 450 units (of urofollitropin, or menotropins plus urofollitropin); treatment >12 days is not recommended; once adequate follicular development is evident, HCG should be administered. Withhold the HCG dose if ovarian monitoring suggests an increased risk of OHSS.

Use in renal and hepatic impairment

The safety and efficacy of this drug have not been established in patients with renal and hepatic failure.

Use in pediatric and elderly patients

The safety and efficacy of this drug have not been established in pediatric and elderly patients.

1. Hypersensitivity to urofollitropin or any component of the formulation

2. High levels of FSH indicating primary ovarian failure

3. Uncontrolled nongonadal endocrinopathies (eg, thyroid, adrenal, or pituitary disorders)

4. Sex hormone–dependent tumors of the reproductive tract and accessory organ

5. Tumors of pituitary gland or hypothalamus

6. Abnormal uterine bleeding of undetermined origin

7. Ovarian cysts or enlargement not due to polycystic ovary syndrome

8. Pregnancy

1. Urofollitropin is a potent gonadotropic substance capable of causing mild to severe adverse reactions, and should only be used under the supervision of physicians who are thoroughly familiar with infertility problems and their management.

   Gonadotropin therapy requires a certain time commitment by physicians and supportive health professionals, as well as the availability of appropriate monitoring facilities. In women, safe and effective use of urofollitropin calls for monitoring of ovarian response with ultrasound, alone or preferably in combination with measurement of serum estradiol levels, on a regular basis. There may be a degree of interpatient variability in response to FSH administration, with a poor response to FSH in some patients. The lowest effective dose in relation to the treatment objective should be used.

   • Treatment in women

   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 urofollitropin dosage and regimen of administration and careful monitoring of therapy will minimize 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 symptomatology may be observed in severe cases of OHSS: abdominal pain, abdominal distension, severe ovarian enlargement, weight gain, dyspnea, oliguria and gastrointestinal symptoms including nausea, vomiting and diarrhea. Clinical evaluation may reveal hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic events.

   Excessive ovarian response to gonadotropin 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 urofollitropin dosage, regimen of administration and careful monitoring of therapy will minimize the incidence of ovarian hyperstimulation and multiple pregnancies. 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 at about seven to ten days following treatment. Usually, OHSS resolves spontaneously with the onset of menses.

   If severe OHSS occurs, gonadotropin treatment should be stopped if still ongoing, the patient hospitalized and specific therapy for OHSS started.

   This syndrome occurs with higher incidence in patients with polycystic ovarian disease.

   • Multiple pregnancy

   Multiple pregnancies, especially high order, carry an increased risk of adverse maternal and perinatal outcomes.

   In patients undergoing ovulation induction with gonadotropins, the incidence of multiple pregnancies is increased compared with natural conception. The majority of multiple conceptions are twins. To minimize the risk of multiple pregnancies, careful monitoring of ovarian response is recommended.

   In patients undergoing ART procedures the risk of multiple pregnancies 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 ovulation induction or ART 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 gonadotropins increases the baseline risk of these tumors 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 recognized risk factors for thromboembolic events, such as 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 gonadotropins. In these women, the benefits of gonadotropin administration need to be weighed against the risks. It should be noted however, that pregnancy itself also carries an increased risk of thromboembolic events.

   • Hypersensitivity

   Hypersensitivity and anaphylactic reactions have been reported; discontinue use for serious reactions and treat appropriately.

Use in pregnancy

The pregnancy category of this drug is X and its use is contraindicated in pregnant women.

Use in breast-feeding

Due to inadequate study on breastfeeding women, it is not recommended during breastfeeding. However, if the benefits of taking medication to the mother are prioritized, the doctor’s decision to prescribe the drug is taken with caution.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects. Adverse effects have been reported in less than 1% of the patients treated with the human recombinant growth hormone, mainly as transitorily reactions over the injection site.

1. Acromegalic features on the face, hands and feet
2. Diabetes
3. Arthrosclerosis
4. Arterial hypertension
5. Carpal tunnel syndrome
6. The development of antibodies
7. Otitis media or hearing conditions in patients with Turner syndrome
8. Gynecomastia
9. Headache
10. Articular and muscular pain
11. Peripheral Edema
12. Pancreatitis
13. Rash
14. Jaundice
15. Intracranial hypertension
16. Lypodystrophy on injection site
17. Hematuria
18. Hypothyroidism

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.”

• Very common (probability of occurrence more than 10 %):

Headache, Abdominal pain

• Common (probability of occurrence of 1 – 10 %):

Urinary tract infection, Nasopharyngitis, Hot flushes, Nausea, Vomiting, Abdominal distension, Abdominal discomfort, Diarrhea, Constipation, Rash, Muscle spasms, Vaginal Hemorrhage, OHSS, Pelvic pain, Breast tenderness, Vaginal discharge, Pain, Injection site pain and reactions (redness, bruising, swelling and/or itching)

• Other complications (uncertainty):

Hypertension, Depression, Emotional changes, Acne vulgaris, Exfoliative dermatitis, Dehydration, Ovarian cyst, Weight gain, Respiratory disease, Sinusitis, Fever

Urofollitropin is a hormone secreted from the gonadotropic cells of the anterior part of the pituitary gland. urofollitropin is a hormone-derived product containing very high purity FSH that is obtained from the urine of a postmenopausal woman and then LH is isolated from it. During the follicular and luteal cycles, FSH secretion in men is constant and in women periodically. FSH stimulates growth, puberty and follicles, and increases the production of estrogen. Therefore, by increasing the proliferation of endometrial cells, it provides the ability to implantation of the fertilized egg.

• This drug is intramuscularly or subcutaneously.

• 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.

1. Keep the medicine in the refrigerator at 2 to 8 °C and protect from freezing.

2. Keep the medicine away from light, heat, moisture and in the original package.

3. Keep away from the sight and reach of children.

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

5. Discard any unused portion.