Follitropin Beta (Subcutaneous)

Overview

Follitropin is prescribed to help women conceive by inducing human-follicle stimulating hormones which increase the production of eggs in the ovaries. Follitropin can also be used to induce pregnancy and ovulation in women with anovulatory infertility when such infertility is the result of a functional cause and not by a failure of the ovaries. Follitropin can also be taken by males to aid in the increase of sperm production.

Folltiropin can be effective in the treatment of infertility, with some studies identifying that 55% of patients became pregnant. The typical time between beginning Follitropin Beta Treatment and pregnancy is three to six months with a host of factors (such as the woman's age and overall health) determining the success of treatment.

Due to the risks involved with hormone treatment, women are to go through extensive gynecologic and endocrinologic testing before the start of treatment. Additionally, women who have experienced primary ovarian failure are not treated with Follitropin Beta.

Type Of Medication

  • Hormone Replacement Therapy

Conditions Treated

Side Effects

Like most medications, Follitropin Beta does come with a significant risk of side effects. If an allergic reaction occurs, the patient should seek emergency medical attention or call the poison control center at (800) 222-1222 Some of these side effects are serious and warrant immediate medical attention if they occur. These side effects are:

  • Severe Abdominal/Stomach Pain
  • Bloating
  • Diarrhea
  • Heavy Vaginal Bleeding (Non-Menstrual)
  • Nausea or Vomiting (Severe)
  • Aching, Discomfort, or Heaviness in Stomach or Pelvis
  • Injection Site Pain, Redness, or Swelling
  • Rapid Weight Gain
  • Unusual Tiredness or Weakness

Additionally, there are some side effects that are less serious and do not require immediate medical attention. These side effects may subside during treatment as the patient's body adjusts to the medication. Additionally, the patient's doctor may be able to instruct the patient on ways to avoid these side effects or reduce their occurrence.

The less serious reactions to follitropin are:

If any side effects other than the ones listed here occur, the patient should contact their caregiver.

Dosage

The dosage and administration of Follitopin Beta depends on its specific use. Patients receiving Follitropin Beta as part of an Assisted Reproductive Technology will receive a starting dose of 150 to 225 IU subcutaneously. The response of their ovaries will determine their dosage for the fifth day onward. Patients who respond positively typically receive maintenance doses of 75 to 300 IU for 6-12 days, or longer if necessary. Patients that responded poorly received maintenance doses in the 375-600 IU range. When a significant presence of follicles of adequate size occurs, hCG is administered at a dose of 5000 IU to 10000 IU to induce the final maturation of Retrieval of the oocytes (eggs), 34 to 36 hours later. In cases where the ovaries are enlarged beyond normal levels, then hGC administration is withheld. This will reduce the risk of OHSS development.

When Follitropin Beta is used for ovulation induction. The starting dose of Follitropin Beta for these patients was 75 IU for 14 days. The intent was to increase the dose in a gradual, stepwise manner. The dosage was then increased by 37.5 IU a week until adequate follicular growth occurs and/or the indication of adequate response by serum estradiol. The maximum daily dose of Follitropin Beta that has been safely used for ovulation induction in patients is 300 IU. The patient should be treated with Follitropin Beta until ultrasonic visualizations and/or serum estradiol levels indicate pre-ovulatory conditions greater than or equal to those in patients with normal ovulation. Once this occurs, the patient should receive a dose of hCG in the 5000 IU to 10000 IU range. As is the case in ART patients, administration of hCG should not occur if the ovaries are enlarged beyond normal levels on the last day of therapy. Withholding hCG will reduce the risk of OHSS.

While the patient is being treated with Follitropin Beta, and for a two week period following treatment, the patient should undergo examinations every other day for indicators of excessive stimulation of the ovaries. If the ovaries become excessively enlarged or if the patient experiences pain in the abdominal region, Follitropin Beta treatment should be stopped. In most cases, OHSS begins after treatment with Follitropin Beta has ceased, and reaches a maximum between 7 and 10 days following ovulation.

Caregivers should encourage the patients to engage in sexual intercourse daily to induce ovulation induction. This should begin the day before the administration of hCG and occur until ovulation becomes apparent from indicators employed for progestational activity determination. Caregivers should only prescribe Follitropin Beta if they are willing to devote considerable time to the patient and familiarize themselves with laboratory studies, including conducting such studies themselves.

Before the Follotropin Beta is injected, the patient or caregiver should examine the container to ensure the liquid is clear and colorless, if it is not, or has any kind of particles in it, it should not be used.

  • Follitropin Beta should be allowed to reach room temperature before injection. Injecting cold Follitropin Beta may cause discomfort.
  • Only the syringe and prescribed needles should be used for the injection.
  • The patient should have the following materials on hand:
  • Alcohol (which should be used with Cotton Balls), or Alcohol Pads/Swabs)
  • Antibacterial Soap
  • Sterile Gauze
  • Safety Container to discard used needles/supplies
  • The injection should be prepared on a clean, dry surface. The patient should wash their hands thoroughly before injection.

The patient should then remove the flip cap from the vial and use an alcohol swab to wipe the rubber stopper. Use a fresh alcohol swab to clean a two inch area around the injection site.

The alcohol should be allowed to dry for at least one minute before injection. Then attach a needle to the syringe. Remove the cap from the needle and pierce it through the vial's rubber stopper. Draw the volume of the Follitropin Beta into the syringe as the caregiver has prescribed.

The syringe should be held in an upward direction and tapping of the sides should occur to force any air bubbles to the top. The plunger should then be squeezed until all air has been expelled and a single drop of Follitropin Beta appears at the needle's tip.

The caregiver will give instructions for subcutaneous injection. The best injection sites are the area below the navel or "bellybutton" or in the upper thigh.

The patient should pick up a large area of skin with their index finger and thumb. The needle should be inserted at a 90 degree angle into this surface.

If the caregiver decides to prescribe Follitropin Beta intramuscularly, the patient may benefit from asking another person for assistance. The upper outer quadrant of the buttock muscle is the best place for intramuscular injection of the drug. The administrator should use the same skin stretching technique as the subcutaneous method for insertion of the needle.

The patient should shift their weight to the leg on the opposite side of the injection site to ensure relaxation of the muscle. The needle should be inserted to its hub, at a 90-degree angle to the surface of the skin.

The syringe must be pulled out quickly, and an alcohol swab should be used to apply pressure to the injection site. The site should be massaged while maintaining pressure to help disburse follitropin beta solution, and for the relief of discomfort.

The syringe and vial should be used only once, and then safely discarded.

If the patient misses a dose, they should simply take their next dose on time as prescribed and not double the dose.

Drug Interactions

Before beginning treatment with any medication, the patient should inform the caregiver of all other medications they're on, as well as any allergies or conditions they have. Follitropin Beta is likely to interact with the following medications

Chasteberry - This natural supplement, used for the treatment of PMS symptoms among other conditions, is known to interact with hormonal drugs such as Follitropin Beta.

Ganirelix - The use of Follitropin Beta concurrently with ganirelix may decrease the effects of Follintropin Beta. If both medications must be taken, a dose adjustment may be required for one of the medications.

Additionally, Follitropin may interact with medications other than the ones listed here. If any such interaction occurs, the patient should notify their caregiver.

Warnings

Only caregivers with significant experience in infertility treatment should treat their patients with Follitropin Beta.

It is recommended that the lowest effective dose of Follitropin be used to reduce possible complications. It is recommended that the patient undergo ultrasound monitoring to test ovarian response and serum estradiol levels.

Follitropin Beta comes with the risk of Ovarian Hyperstimulation Syndrome. This can occur with or without vascular or pulmonary complications. Multiple births are also a possible effect of OHSS caused by Follitropin Beta. The condition is characterized by a rapidly occurring accumulation in fluid within the peritoneal cavity, thorax, and likely the pericardium. This results from a massive increase in vascular permeability. OHSS may cause the following symptoms

  • Abdominal Distention
  • Abdominal Pain
  • Acute Pulmonary Distress
  • Ascites
  • Diarrhea
  • Dyspnea
  • Electrolyte
  • Hemoconcentration
  • Hemoperitoneum
  • Hydrothroax
  • Hypo-Voluemia
  • Nausea/Vomiting
  • Ovarian Enlargement
  • Oliguria
  • Pleural Effusions
  • Thromboembolic Events
  • Weight Gain

OHSS can be avoided if the ovaries are checked for excessive enlargement on the last day of Follitropin Beta treatment. If they are found to be excessively large, withholding the hCG dose will prevent the development of OHSS. Usually OHSS develops after Follitropin Beta has been discontinued, with a peak of around 7-10 days before treatment. OHSS typically resolves itself upon the start of the woman's next period.

If a major case of OHSS occurs, the caregiver should immediately stop Follitropin treatment and hospitalize the patient. Symptomatic treatment should occur. This consists of:

  • Analgesics (if necessary)
  • Bed Rest
  • Fluid and Electrolyte Management

The physician should test for hemoconcentration indicative of the loss of fluid into the peritoneal cavity, or the peritoneum pleural cavity. Assessment should be carried out in the following manner

1. Measurement of Intake/Output of Fluid
2. Measurement of Weight
3. Measurement of Hematocrit
4. Measurement of Urinary Electrolytes and Serum
5. Measurement of Specific Gravity or Urine
6. Measurement of BUN and Creatine
7. Measurement of Total Proteins with Albumin
8. Studies of Coagulation
9. Monitoring for Hyperkalemia with Electrocardiogram
10. Girth in abdominal region

These assessments should take place daily or more often if necessary.

OHSS increases the risk of ovarian injury. The physician should not remove Ascitic, pleural, and pericardial fluid, unless doing so is necessary to relieve conditions such as cardiac tamponade or pulmonary distress. Pelvic examinations should be avoided, as it can induce hemoperitoneum due to rupture of an ovarian cyst. Upon occurrence of bleeding that requires surgery, the objective should be to control bleeding while retaining the maximum amount of ovarian tissue possible. Patients with severe enlargement of the ovaries should be prohibited from having sexual intercourse, due to the high risk of hemoperitoneum from the rupture of an ovarian cyst.

Management of Ovarian Hyperstimulation Syndrome is a three phase process

Acute Phase: The caregiver should direct management at the prevention of hemoconcentration due to intravascular volume loss to the third space. The caregiver should also work to minimize the risk of damage to the kidneys and thromboembolic phenomena. Treatment is intended for the normalization of electrolytes and maintaining intravascular volume at an acceptable, but slightly reduced level. Completely correcting the intravascular volume deficit may cause the accumulation of third space fluid to reach an unacceptable level.

Chronic Phase: During the chronic phase, which occurs after patient stabilization, severe restriction of fluid, sodium, and potassium should occur to limit excessive accumulation of fluid in the third space.

Resolution Phase: This phase is marked by the third space fluid returning to the intravascular compartment. This is indicated by an increase in urinary output and a drop in hematocrit. Edema, both peripheral and pulmonary, could result if the kidneys are unable to increase third space fluid as rapidly as it is moblized. If necessary, diuretics may be prescribed to treat edema during the resolution phase.

Women treated with gonadotropins have been known to suffer serious pulmonary conditions (such as acute respiratory distress syndrome and atelectasis. Thrombo-embolic events have also occurred in patients receiving gonadotropin treatment. These have occurred both separate from and in concurrence with cases of Ovarian Hyper-Stimulation syndrome. Intravascular thrombosis, originating in arterial or venous vessels can create a reduction in blood flow to extremities and vital organs. Events that have occurred in association with Follitropin Beta are as follows:

The risk of multiple births resulting from Follitropin Beta is high. The caregiver should inform the patient and their partner of this risk before Follitropin Beta treatment starts.

The diagnosis of infertility should receive careful attention. Candidates for Follitropin Beta should be selected with great care.

Most cases of Follitropin Beta treatment will result only in the growth and maturation of ovarian follicles. hCG must be given to the patient upon the conclusion of Follitropin Beta treatment or when maturation of the follicles is determined to have occurred. Visualization of the ovaries and endometrial lining and/or measuring serum estradiol levels. The combination of both these measures is a great tool in the monitoring of follicle growth and development. It can also aid in the timing of hCG administration as well as minimize the risk of OHSS and multiple gestations.

Progesterone production confirms ovulation through direct and indirect indicators. The most commonly used of these are as follows:

  • An increase in the patient's basal body temperature
  • An increase in the patient's serum progesterone
  • The patient beginning menstruation following the shift in basal body temperature.

Sonographic visualization, used in concurrency with these indicators, will aid the patient in determining the occurrence of ovulation. Evidence of ovulation may include the following.

  • The presence of fluid in the cul-de-sac
  • A marked decrease in the size of the follicle
  • Collapsed follicle

Long-term studies to evaluate toxicity in animals have not been performed. An Ames test using S. Typhimurium and E. Coli tester strains did not produce chromosomal aberrations in an in vitro assay.

However, it is not known if a nursing infant will be harmed by Follitropin Beta. However, due to the potential for serious harm to the baby if Follitropin is secreted in breast milk, the woman should choose between breastfeeding and taking Follitropin Beta.

The only symptom of Follitropin Beta overdose is the aforementioned Ovarian Hyperstimulation Syndrome.

  • Follitropin Beta is contraindicated in the following patients:
  • Women who exhibit prior sensitivity to hFSH products
  • Women who exhibit high levels of FSH, which indicates primary ovarian failure
  • Adrenal or Thyroid Dysfunction of an uncontrollable level

Tumors in the following areas:

  • Breast
  • Hypothalamus
  • Ovaries
  • Pituarity Grand
  • Uterus
  • Women who are already pregnant
  • Vaginal Bleeding of a heavy, irregular nature, with no known cause
  • Enlargement of the Ovaries, Cysts on the Ovaries

Hypersensitive Reactions to Streptomycin or Neomycin. It is possible for Follitropin Beta to contain traces of these antibiotics, and cause hypersensitive reactions in those who are susceptible to them.

Storage

The patient's caregiver will provide them with instructions on how to store Follitropin Beta containers. The containers should be kept away from light. Children and pets should not have access to Follitropin Beta. It should be kept in a safe place, and discarded using proper measures.

Summary

Follitropin Beta can be an effective aid in a helping a woman become pregnant. Its promotion of the growth and development of ovarian follicles in females, and spermatogenesis in males has been proven to help couples conceive a child. However, the success depends heavily on several factors, including the overall health of both the woman and her partner, her age, and her primary ovarian function. Follitropin is not a guaranteed success.

Follitropin Beta, like any hormonal treatment, is a powerful substance. Careful evaluation and examination of the woman must be performed by her caregiver. The caregiver should be one with extensive experience in infertility treatment. They should be willing to consistently monitor the patient's progress and watch for any signs of complication. They should be well versed in all scientific studies regarding the drug, and willing to participate in such studies themselves. Follitropin Beta carries a very high risk of Ovarian Hyperstimulation Syndrome (OHSS), and caregivers should always be looking for signs of this condition. If OHSS occurs, Follitropin Beta should be immediately discontinued, and the supplemental hCG injection should not take place. OHSS should then be treated based on its symptoms. Other possible adverse effects of Follitropin include cardiovascular and pulmonary issues.

Follitropin Beta can be a beneficial treatment for infertility, but it can also pose great danger if all parties are not careful in the administration of the drug.