Follitropin delta (recombinant human follicle-stimulating hormone) is a recombinant human DNA follicle stimulating hormone that is used to stimulate follicular development in females with ovarian failure.

Follitropin delta (Rekovelle) Uses:

Note: Not approved for use in the US.

• Multifollicular development during assisted reproductive technology:

  • Used to stimulate the development of multiple follicles in women undergoing assisted reproductive technology (ART)

Follitropin delta (Rekovelle) Dose in Adults

Note: Dose should be individualized. The lowest dose consistent with the expectation of good results should be used. Over the course of treatment, doses may vary depending on the response of every patient.

Follitropin delta (Rekovelle) multi follicular development during assisted reproductive technology (ART): SubQ:

Note:

• For the 1st treatment cycle, individual daily doses are selected according to serum anti-Mullerian hormone (AMH) levels and body weight (measured without shoes and coat just prior to the start of stimulation).
• Maintain the individual daily dose throughout the stimulation period. Adequate follicular development is generally achieved by the 9th day of treatment (range: 5 to 20 days).

• First treatment cycle:

  • AMH <15 pmol/L (irrespective of body weight): 12 mcg/day.
  • AMH ≥15 pmol/L: Dose depends upon AMH levels (expressed in pmol/L); daily dose decreases from 0.19 to 0.1 mcg/kg by increasing AMH levels. For detailed dosing information see manufacturer labeling.
  • Maximum dose: 12 mcg/day.

Note: As soon as ≥3 follicles ≥17 mm are observed, administer hCG to induce final follicular maturation. If there is an excessive ovarian response by the patient  (>25 follicles with diameter ≥12 mm) final follicular maturation with hCG should not be induced and the cycle should be canceled.

• Subsequent treatment cycles:

Note: Dose is based on the response of the ovary to the previous cycle.

• • If the response is adequate, a daily dose should be maintained.
  • Hypo-response: Dose may be increased by 25% based on the extent of response.
  • Hyper-response: Health care providers should be consulted as limited data is available.
  • Maximum dose: 24 mcg per 24 hours.

• Missed doses:

  • In case of a missed dose, the next dose should not be doubled; health care providers monitoring treatment should be notified.

Use in Children:

Not indicated.

Follitropin delta Pregnancy Risk Category: D

• Follitropin Delta is used to induce ovulation. It should not be used by females who are pregnant.
• Multiple births, congenital abnormalities, ectopic pregnancy and spontaneous abortion have all been reported.
• Congenital abnormalities can occur at a higher rate with assisted reproductive technology (ART), than with spontaneous conception.
• Parenteral characteristics (maternal and sperm characteristics, maternal age) could also play a role in the higher incidence.
• Treatment may be modified to decrease the risk of ovarian hyperstimulation syndrome, if there is an abnormal ovarian enlargement.
• If this is the case, you should advise patients to stop having intercourse and to use barrier contraceptive methods at least for 4 days.

Use during breastfeeding:

• It is unknown if breast milk contains follitropin delta.
• Breastfeeding is not recommended when Follitropin delta has been used.

Dose in Kidney Disease:

No dosage adjustments have been provided in the manufacturer's labeling.

Dose in Liver disease:

No dosage adjustments have been provided in the manufacturer's labeling.

Less Common Side Effects of Follitropin delta (Rekovelle):

• Central Nervous System:

  • Headache
  • Fatigue
  • Nipple Pain

• Endocrine & Metabolic:

  • Ovarian Hyperstimulation Syndrome

• Gastrointestinal:

  • Nausea

• Genitourinary:

  • Pelvic Cramps
  • Pelvic Pain
  • Uterine Pain

• Hematologic & Oncologic:

  • Polyp

• Immunologic:

  • Antibody Development

Contraindications to Follitropin delta (Rekovelle):

• Hypersensitivity to follitropins and any component of the formulation
  • Tumors of the breast, ovary, uterus or pituitary gland
  • Pregnancy
  • Breastfeeding
  • Undetermined source of gynecologic bleeding
  • Ovarian cysts and enlargements not caused by PCOS (polycystic-ovary syndrome)
  • Primary ovarian failure
  • Incompatible with pregnancy: Malformations of the sexual organs
  • Fibroid tumors in the uterus are incompatible with pregnancy

Warnings and precautions

• Abortion

  • Gonadotropins increase the chance of spontaneous abortion, but a causal relationship has not been established.

• Ectopic pregnancy

  • Women with tubal abnormalities may be at greater risk of ectopic pregnancy. An early ultrasound is recommended to confirm intrauterine pregnancy.

• Ovarian enlargement:

  • To reduce the risk of ovarian hyperstimulation syndrome, (OHSS), withhold hCG if there is abnormal ovarian enlargement.

• Ovarian hyperstimulation syndrome:

  • This is rare and can be life-threatening.
  • It can occur within one day, but it may get worse 7-10 days after treatment.
  • Abdominal distention/discomfort, diarrhea, nausea, and/or vomiting are few symptoms of mild/moderate OHSS.
  • Severe OHSS can present with severe abdominal pain, severe dyspnea or hypotension, ascites, severe anuria/oliguria and ascites, severe dyspnea or nausea/vomiting (intractable).
  • You may also experience decreased creatinine clearance, hemoconcentration and hypoproteinemia.
  • The mainstay of treatment is fluid and electrolyte management. Supportive care is also available. Prevention of thromboembolic complications
  • Stop using gonadotropin therapy

• Ovarian neoplasms

  • Women who have received multiple-drug therapy for controlled hormonal stimulation (multiple-drug therapy) have occasionally been diagnosed with benign and malignant neoplasms. However, the causal relationship has not been established.

• Ovarian torsion

  • Ovarian torsion has been reported following gonadotropin treatment. This could be due to OHSS or previous ovarian cysts, pregnancy or abdominal surgery.
  • Early diagnosis and prompt detorsion can help to limit the extent of ovarian damage.

• Effects on the pulmonary system:

  • Gonadotropin therapy can cause severe pulmonary conditions (atelectasis and acute respiratory distress syndrome, as well as exacerbation or asthma).

• Thromboembolic disorders

  • Women with a history or current thromboembolic disorder or risk factors (eg family history, severe obesity, thrombophilia) are at greater risk of developing or worsening arterial or venous thromboembolic events. This risk may be increased by gonadotropin treatment.

Monitoring parameters:

Prior to therapy:

• Pregnancy and primary ovarian failure should be ruled out
• Endocrinologic and gynecologic assessment (including pelvic anatomy)
• Fertility potential of partner
• Serum anti-Mullerian hormone (AMH) to determine the initial dose

(Note: Manufacturer has recommended the use of Elecsys AMH immunoassay to determine levels).

During therapy:

• Monitoring should be done for sufficient follicular maturation.
• This may be estimated directly by visualization of the ovaries and endometrial lining via ultrasound or measuring serum estradiol levels.
• The combination of both ultrasonography and measurement of estradiol levels is useful to monitor the growth and development of follicles and timing hCG administration.
• Signs and symptoms of ovarian hyperstimulation syndrome (OHSS) should be monitored at least 2 weeks following hCG administration.
• Abdominal distention/discomfort, diarrhea, nausea, and/or vomiting may be classified as mild/moderate OHSS symptoms.
• Whereas, severe abdominal pain, anuria/oliguria, ascites, severe dyspnea, hypotension, or nausea/vomiting (intractable) may be classified as severe OHSS symptoms.
• Decreased creatinine clearance, hemoconcentration, hypoproteinemia, elevated liver enzymes, elevated WBC, and electrolyte imbalances may also be present.

How to administer Follitropin delta (Rekovelle)?

Subcutaneous:

• Should be administered subcutaneously preferably in the abdomen.
• Administer the first injection under the supervision of a health care provider; self-administration of subsequent injections by the patient is at the discretion of the monitoring prescriber.
• Use prefilled cartridges in conjunction with the Rekovelle injection pen.

Mechanism of action of Follitropin delta (Rekovelle):

• Follitropin Delta is a human Follicle-stimulating Hormone (FSH) that has been prepared from recombinant DNA. 
• Women who are not experiencing primary ovarian failure can be stimulated by follitropins.

The onset of action:

• Peak effect: Follicle development: Within cycle

Bioavailability:

• Subcutaneous: ~64%

Half-life elimination:

• Subcutaneous: 40 hours (single dose); 28 hours (daily administration)

Time to peak:

• Subcutaneous: 20 hours (single dose); 10 hours (once-daily administration for 7 days)

International Brand Names of Follitropin delta:

• Rekovelle
• Follitrope
• Gonadopin
• Revove

Follitropin delta Brand Names in Pakistan:

No Brands Available in Pakistan.