Follimon™ Inj. (Purified FSH)

Brand Name
Follimon™ Inj. (Purified FSH)
Generic Name
(Urofollitropin 75 IU)
Therapeutic Segment
Obstetrics & Gynecology, Infertility
Form
Injection

Follimon is a preparation of follicle stimulating hormone (FSH, Urofollitropin) extracted and purified from the urine of post-menopausal women. FSH is the hormone produced by the anterior pituitary gland, which acts on the ovaries to cause follicular development and Follimon can be used to induce follicular development in the treatment for infertility.

As Follimon is nearly devoid of LH, Follimon is a safe infertility treatment reducing likelihood of unpleasant side effects such as ovarian hyper stimulation syndrome (OHSS) and spontaneous abortion and human chorionic gonadotropin (HCG, IVF-C) must be given following the administration of Follimon, once follicular maturation has occurred.

Composition

Each vial of Follimon inj. is accompanied by a solvent vial or ampoule containing 1 ml of isotonic, sterile and pyrogen-free sodium chloride for injection.

1 vial of Follimon contains

Active ingredient : Urofollitropin(BP) …………………………………………… 75 IU
Excipient : Lactose monohydrate …………………………………… 10.0 mg

Description

White lyophilized powder for injection in a clear vial.

Indications and usage

Dosage and Administration

Ovulation induction

Although the initial recommended dose must be individualized, 1 vial of Follimon (Urofollitropin 75 IU) per day should be administered intramuscularly for 7-12 days and 5000-10000 IU of HCG(IVF-C) must be followed one day after the last day of urofollitropin.

If follicular maturation is insufficient, urofollitropin can be administered more than 12 days until estrogenic activity turns higher than healthy normal women.

In case ovary is abnormally enlarged at the point of completion of urofollitropin treatment, HCG should not be administered.

If there is evidence of ovulation but not pregnancy, repeat tins dosage regimen for at least 2 more courses and increase the dose of urofollitropin to 150 IU/day (2 vials)for 7-12 days and administer 5000 – 10000 IU of HCG(IVF-C) one day after the last administration of urofollitropin.

lf there is evidences of ovulation but pregnancy does not ensue, repeat the same dose for 2 courses.

Doses larger than this are not recommended.

External Fertilization

2 vials of urofollitropin(150 IU) should be continued to be administered until enough follicular maturation occurs in early follicular phase(Cycle 2, 3). Generally treatment period does not exceed 10 days.

How to use

1 vial of urofollitropin should be dissolved in 1-2 ml of the accompanied sterile sodium chloride for injection and administered intramuscularly immediately. Remained solution should not be reused.

Warnings and Precautions

1. Contra-indications

  1. High level of LH and FSH indicating primary ovarian failure
  2. Thryroid and adrenal dysfunction
  3. lntracranial lesion such as pituitary tumor
  4. Any cause of infertility other than anovulation
  5. Ovarian cysts and enlargement not due to polycystic ovary
  6. Hypersensitivity to urofollitropin
  7. Pregnant women

2. Warnings

Urofollitropin should be used only by physicians who have experiences in infertility problems and since it is possible that mild to severe adverse reactions are caused, patients should be appropriately monitored.

Overstimulation of ovary may occur.

Ovarian enlargement

Mild ovarian enlargement accompanied by abdominal distension and abdominal pain may occur in about 20% of patients treated with urifollitropin and HCG but naturally regress within 2-3 weeks. To avoid it, minimum operative amount of urofollitropin should be used and cautious monitoring on ovarian reaction is necessary.

If abnormal ovarian enlargement is shown in the anaphase of urifollitropin administration, HCG administration should be withheld.

Ovarian Hyper-stimulation Syndrome (OHSS)

OHSS is characterized by rapid progress and cause fluid infusion in the peritoneal cavity, thorax, and pericardium resulted from the increase in vascular permeability. Early symptoms of the OHSS are severe pelvic pain, nausea, vomiting, and weight gain.

Following symptoms may occur: abdominal pain, abdominal distension, gastrointestinal symptoms including nausea, vomiting, and diarrhea, severe ovarian enlargement, weight gain, dyspnea, oliguria, hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hemopericardium, pleural effusions, hydrothorax, acute pulmonary distress, thrombus.

OHSS occurs in approximately 6% of anovulatory patients treated with urofollitropin and 0.25% of external fertilization.

Because OHSS can develop rapidly, patients should be monitored for at least 2 weeks after HCG administration.

OHSS generally resolves with the onset of menses.

If OHSS occurs, treatment should be stopped and the patient hospitalized being given primarily symptomatic treatment consisting of bed rest, fluid and electrolyte management, and analgesics administration.

lf the phenomenon of hemoconcentration associated with fluid loss occurs, (1)fluid intake and output (2) weight (3) hematocrit (4) serum and urinary electrolytes (5) urine specific gravity (6) BUN and creatinine (7) abdominal girth should be assessed daily or often. A risk of injury to the ovary increases with OHSS.

Pelvic examination may cause rupture of an ovarian cyst resulting in hemoperitoneum and should therefore be avoided. If bleeding occurs, the surgical treatment should be designed to control bleeding and to retain ovarian tissues. In case significant ovarian enlargement occurs after ovulation, intercourse should be prohibited because of the danger of hemoperitoneum resulting from ruptured ovarian cysts.

The treatment of OHSS is divided into three phases. Because the use of diuretics can accelerate the diminished intravascular volume, diuretics should be avoided except in the late phase of resolution.

Acute Phase: Management during the acute phase should be designed to prevent hemoconcentration, thromboembolic phenomena, and kidney damage. Control reduced intravascular volume and normalize electrolytes.

Monitoring for the development of hyperkalemia is recommended.

Stable Phase: After stabilizing the patient during the acute phase, manage excessive fluid accumulation in abdominal cavity, thoracic cavity, and pericardium by instituting severe potassium, sodium, and fluid restriction.

Resolution Phase: A fall in hematocrit and an increasing urinary output may be observed due to the return of the fluid of abdominal cavity, thoracic cavity, and pericardium to the intravascular compartment.

Pulmonary and vascular complications may happen.(atelectasis, acute respiratory distress syndrome, thrombosis both in associated with and separate from OHSS) This may cause sequelae such as venous thrombophlebitis, pulmonary embolism, pulmonary infarction, cerebral vascular occlusion, and arterial occlusion, etc. and very rarely result in death.

It has been reported that multiple birth is associated with urofollitropin therapy. In clinical studies with urofollitropin, 83% of the pregnancies following therapy resulted in single births and 17% in multiple births.

The patient and her husband should be informed of the potential risk of multiple births before starting therapy.

3. Precautions

General Precautions

Sufficient examinations should be made before urofollitropin therapy. Prior to therapy, patients should be informed of the duration of treatment, required monitoring of their condition, possible adverse reactions, and the risk of multiple births.

Laboratory Tests

Since treatment with urofollitropin in most instances results in follicular growth and maturation, the status of sufficient follicular maturation should be monitored in case HCG is administered in order to induce ovulation.

Direct measurements such as the measurement of serum (or urinary) estrogenic activity and sonographic visualization of the ovaries are performed to determine the timing of HCG administration and to estimate the risk of OHSS and multiple gestation, and following indirect parameters may be combined.

Examinations of changes in the vaginal cytology, appearance and volume of the cervical mucus, spinnbarkeit, ferning of the cervical mucus, and ovulation are to get indicated of progesterone production and a rise in basal body temperature, increase in serum progesterone, and menstruation following the shift in basal body temperature are the indices generally used and fluid in the cul-de-sac, ovarian stigmata, and collapsed follicle may also be sonographic evidences of ovulation.

Although no clinically significant drug-drug interactions, carcinogenicity, and mutagenicity have been reported during urofollitropin therapy and it is not known whether this drug is excreted in human milk, caution should be exercised in case of administering this drug to a nursing mother as many other drugs.

4. Adverse Effects

Ovarian hyper stimulation, mild ovarian enlargement, ovarian cysts, abdominal pain, hypersensitivity, gastrointestinal symptoms, irritation at site of injection like pain, rash, and swelling, breast tenderness, headache, and dermatological symptoms may occur.

Ectopic pregnancy, congenital abnormalities, pulmonary and vascular complications, and ascetic bleeding may occur.

How Supplied: 1, 3, 5, 10, 20, 50 vials with solvent vials or ampoules/pack.

Storage Condition: Store below 25 ° C.

Shell Life: 24 months.