Follitropin Alfa (r-hFSH)/ Lutropin Alfa (r-hLH)

Registered South African indications:

• Stimulation of follicular development in adult women with severe LH and FSH deficiency

Contraindications

Registered contraindications in South Africa & other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients
• Tumours of the hypothalamus and pituitary gland
• Ovarian enlargement or ovarian cyst unrelated to polycystic ovarian disease and of unknown origin
• Gynaecological haemorrhages of unknown origin
• Ovarian, uterine, or mammary carcinoma

Follitropin alfa/ lutropin alfa must not be used when an effective response cannot be obtained, such as:

• Primary ovarian failure
• Malformations of sexual organs incompatible with pregnancy
• Fibroid tumors of the uterus incompatible with pregnancy

Cautions

• Renal impairment (South African recommendations)
• Hepatic impairment (South African recommendations)
• Porphyria or family history thereof 
• Hypothyroidism
• Adrenocortical deficiency
• Hyperprolactinemia
• Polycystic ovarian syndrome
• Young age 
• Lean body mass
• High doses
• Previous episodes of ovarian hyperstimulation syndrome
• Large number of developing ovarian follicles 
• Previous abdominal surgery
• History of ovarian torsion
• Previous or current ovarian cyst
• History of tubal disease
• Multiple regimens
• Recent or ongoing thromboembolic disease
• Risk factors for thromboembolic events

Forms avail. in SA and covered in this monograph: inj, pfp

South African registered indications and dosages

Treatment with follitropin alfa/ lutropin alfa should be initiated under the supervision of a physician experienced in the treatment of fertility problems

Stimulation of follicular development in adult women with severe LH and FSH deficiency (Additional agent(s) required)
- In clinical trials, these patients were defined by an endogenous serum LH level <1.2 IU/L

A treatment regimen commences with the recommended dose of follitropin alfa/ lutropin alfa containing 150 IU r-hFSH/75 IU r-hLH daily

Follitropin Alfa/ Lutropin Alfa
150/75 (IU per vial)

• SC: Initial: 1 vial, dly; If less than the recommended dose daily is used, the follicular response may be unsatisfactory because the amount of lutropin alfa may be insufficient

Follitropin Alfa/ Lutropin Alfa
300/150 (IU/0.48ml)
900/450 (IU/1.44ml)

• SC: If an FSH dose increase is deemed appropriate: Titrate by 37.5-75 IU of follitropin alfa preferably after 7-14 days; Max treatment duration: Acceptable to extend duration of stimulation up to 5 weeks/cycle
  THEN: When an optimal response is obtained, a single injection of 250𝜇g of r-hCG or 5000-10000 IU (five thousand to ten thousand IU) of hCG should be administered 24-48hrs after the last follitropin alfa/ lutropin alfa injection; The patient is recommended to have coitus on the day of, and on the day following hCG administration OR intrauterine insemination (IUI) may be performed

In LH and FSH deficient women (hypogonadotrophic hypogonadism), the objective of follitropin alfa/ lutropin alfa therapy is to develop a single mature Graafian follicle from which the oocyte will be liberated after the administration of human chorionic gonadotrophin (hCG)

Follitropin alfa/ lutropin alfa should be given as a course of daily injections. Since these patients are amenorrhoeic and have low endogenous oestrogen secretion, treatment can commence at any time. Treatment should be tailored to the individual patient’s response as assessed by measuring follicle size by ultrasound and oestrogen response

Luteal phase support may be considered since lack of substances with luteotrophic activity (LH/hCG) after ovulation may lead to premature failure of the corpus luteum. If an excessive response is obtained, treatment should be stopped and hCG withheld. Treatment should recommence in the next cycle at a dose of FSH lower than that of the previous cycle

The first injection should be performed under direct medical supervision. Self-administration should only be performed by patients who are well motivated, adequately trained and with access to expert advice

• Not indicated for use in children

Pregnancy

Recommendations below are applicable to South Africa and other jurisdictions

• Not indicated for use in pregnant women
• Data on a limited number of exposed pregnancies indicate no adverse reactions of follitropin alfa and lutropin alfa on pregnancy, embryonal or foetal development, parturition or postnatal development following controlled ovarian stimulation
• No teratogenic effect of such gonadotropins has been reported in animal studies. In case of exposure during pregnancy, clinical data are not sufficient to exclude a teratogenic effect of follitropin alfa/ lutropin alfa

Breastfeeding

Recommendations below are applicable to South Africa and other jurisdictions

• Not indicated for use in breastfeeding women

Fertility

Recommendations below are applicable to South Africa and other jurisdictions

• Indicated for use in infertility

Recommendations below are applicable to South Africa and other jurisdictions

• Caution; no information available

Recommendations below are applicable to South Africa and other jurisdictions

• Caution; no information available

Recommendations below are applicable to South Africa and other jurisdictions

• Not indicated for use in geriatric patients

Central Nervous System Disorders

• Headache

Cardiovascular Disorders

• Thromboembolism 

Respiratory Disorders

• Exacerbation or aggravation of asthma

Gastrointestinal Disorders

• Abdominal pain
• Abdominal distension
• Abdominal discomfort
• Nausea and vomiting
• Diarrhoea

Genitourinary Disorders

• Ovarian cysts
• Ovarian hyperstimulation syndrome 
• Pelvic pain
• Breast pain 

Skin and Subcutaneous Tissue Disorders

• Local injection site reactions

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
• Anaphylactic reactions
• Anaphylactic shock

No information available 

• Luteinising hormone levels
• Follicle stimulating hormone levels
• Ultrasound
• Estradiol level 
• Signs and symptoms of ovarian hyperstimulation syndrome 

Lutropin alfa is a recombinant human luteinising hormone, a glycoprotein composed of non-covalently bound alpha- and beta-subunits. In the stimulation of follicular development in anovulatory women deficient in luitinizine hormone and follicle stimulating hormone (FSH), the primary effect resulting from administration of lutropin alfa is an increase in oestradiol secretion by the follicles, the growth of which is stimulated by FSH. Follitropin is a recombinant form of endogenous follicle stimulating hormone (FSH). FSH binds to the follicle stimulating hormone receptor which is a G-coupled transmembrane receptor. Binding of the FSH to its receptor seems to induce phosphorylation and activation of the phosphatidylinositol-3-kinase (PI3K) and Akt signaling pathway, which is known to regulate many other metabolic and related survival/maturation functions in cells.

COMBINATION PREPARATIONS

Follitropin alfa/ Lutropin alfa

Injection (per vial) 150iu/75iu

• Pergoveris (Merck) originator