Recombinant human follicle-stimulating hormone (recombinant human follitropin delta) is a hormone made from recombinant human DNA that is used to promote 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 encourage the growth of many follicles in female users of assisted reproductive technology (ART)

Follitropin delta (Rekovelle) Dose in Adults

Note: Individual dosage should be used. Use the lowest dose that yet leaves room for positive outcomes. Depending on how each patient responds, doses may change throughout the course of treatment.

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

Note:

• Individual daily doses are chosen for the first treatment cycle based on body weight and serum anti-Mullerian hormone (AMH) levels (measured without shoes and coat just prior to the start of stimulation).
• Throughout the stimulation time, continue to provide the specific daily dose. By the ninth day of pregnancy, enough follicular growth is typically attained.

• First treatment cycle:

  • AMH <15 pmol/L (irrespective of body weight): 12 mcg/day.
  • AMH ≥15 pmol/L: The daily dose drops from 0.19 to 0.1 mcg/kg by raising AMH levels, which are represented in pmol/L. See the manufacturer's package for complete dosage instructions.
  • Maximum dose: 12 mcg/day.

Note: Give hCG to encourage ultimate follicular maturation as soon as three follicles or more that are 17 mm in diameter are seen. Final follicular maturation with hCG should not be induced and the cycle should be stopped if the patient exhibits an excessive ovarian response (>25 follicles with a diameter of 12 mm).

• Subsequent treatment cycles:

Note: The 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: The dose may be increased by 25% based on the extent of the response.
  • Hyper-response: Healthcare 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; healthcare 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.
• There have been reports of multiple births, congenital anomalies, ectopic pregnancies, and spontaneous abortions.
• 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 for at least 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:

  • Withhold hCG if there is abnormal ovarian enlargement in order to lower the risk of ovarian hyperstimulation syndrome (OHSS).

• 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

  • Multiple-drug therapy for regulated hormonal stimulation in women has occasionally resulted in the diagnosis of benign and malignant neoplasms. The causal link has not yet been proven, though.

• Ovarian torsion

  • There have been reports of ovarian torsion after gonadotropin therapy. This might be a result of OHSS, old ovarian cysts, becoming pregnant, or having abdominal surgery.
  • The extent of ovarian injury can be reduced with early detection and quick detorsion.

• Effects on the pulmonary system:

  • Treatment with gonadotropins may result in serious pulmonary problems (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:

• It is important to keep an eye out for adequate follicular maturation.
• This can be determined directly by using ultrasonography to see the ovaries and endometrial lining or by checking the blood estradiol levels.
• To track the development of follicles and time the administration of hCG, it is helpful to combine ultrasonography and the measurement of estradiol levels.
• At least two weeks after hCG treatment, ovarian hyperstimulation syndrome (OHSS) symptoms and signs should be watched for.
• Mild/moderate OHSS symptoms include abdominal distention/discomfort, diarrhoea, nausea, and/or vomiting.
• On the other hand, severe OHSS symptoms include anuria/oliguria, ascites, severe dyspnea, hypotension, and nausea/vomiting (intractable).
• Hemoconcentration, decreased creatinine clearance,

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):

• A human follicle-stimulating hormone (FSH) called follitropin delta was created from recombinant DNA.
• Follitropins can stimulate females who do not have primary ovarian insufficiency.

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.