Lutropin Alfa

G03G - Gonadotropins and other ovulation stimulants ATC G03GA07 Protein approved 2000 Parenteral

JFDA label: Luveris

Mechanism of Action

Agonist of Lutropin-choriogonadotropic hormone receptor — Luteinizing hormone/Choriogonadotropin receptor agonist

Target	Action	Gene / class
Lutropin-choriogonadotropic hormone receptor efficacy	AGONIST	LHCGR

Indications

Approved

Infertility

Contraindications

Source: Lexicomp

Hypersensitivity to lutropin alfa or any component of the formulation Absolute
abnormal uterine bleeding of undetermined origin Absolute
active, untreated tumors of the hypothalamus and pituitary gland Absolute
breastfeeding Absolute
fibroid tumors of the uterus incompatible with pregnancy Absolute
malformations of sexual organs incompatible with pregnancy Absolute
ovarian cyst or enlargement unrelated to polycystic ovarian disease and of undetermined origin Absolute
ovarian, uterine, or breast cancer Absolute
primary ovarian failure Absolute
uncontrolled thyroid or adrenal dysfunction Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (3)

Very Common Headache · pain

Common Fatigue

Hepatobiliary disorders (2)

Common Increased serum ALT · increased serum AST

Renal and urinary disorders (2)

Very Common Dysmenorrhea · mastalgia

Metabolism and nutrition disorders (4)

Very Common Ovarian cyst

Common increased serum cholesterol · ovarian disease · Ovarian hyperstimulation

Gastrointestinal disorders (5)

Very Common abdominal pain · Flatulence

Common constipation · diarrhea · Nausea

General disorders and administration site conditions (1)

Common Injection site reaction

Respiratory, thoracic and mediastinal disorders (1)

Common Upper respiratory tract infection

Dosing

Source: Lexicomp

Infertility: Females (≥16 years to ≤60 years): SubQ: 75 units daily until adequate follicular development is noted (maximum dose: 75 units daily); maximum duration of treatment: 14 days, unless signs of imminent follicular development are present. Duration of stimulation may be extended in any one cycle up to 5 weeks (treatment should be individualized based on response to prior cycle). Administer concomitantly with follitropin alfa. Administer hCG one day after the last dose of lutropin alfa and follitropin alfa. Encourage patients to have daily intercourse beginning the day prior to hCG administration and until ovulation is apparent. If the ovaries are abnormally enlarged or if abdominal pain occurs, withhold hCG, discontinue lutropin alfa and follitropin alfa, and advise patient to avoid intercourse.

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Warnings & Precautions

Source: Lexicomp

Neoplasm

Benign and malignant neoplasms have been reported with multiple drug infertility treatment; causative association between gonadotropin therapy and increased risk of malignancy has not yet been established.

Ovarian enlargement

May be accompanied by abdominal distention or abdominal pain and generally regresses without treatment within 2 to 3 weeks; more common in women with polycystic ovarian syndrome. If ovaries are abnormally enlarged on the last day of treatment, withhold hCG to reduce the risk of ovarian hyperstimulation syndrome (OHSS).

Ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is a rare exaggerated response to ovulation induction therapy (Corbett 2014; Fiedler 2012). This syndrome may begin within 24 hours of treatment but may become most severe 7 to 10 days after therapy (Corbett 2014). Symptoms of mild/moderate OHSS may include abdominal distention/discomfort, diarrhea, nausea, and/or vomiting. Severe OHSS symptoms may include severe abdominal pain, anuria/oliguria, ascites, severe dyspnea, hypotension, or nausea/vomiting (intractable). Decreased creatinine clearance, hemoconcentration, hypoproteinemia, elevated liver enzymes, elevated WBC, and electrolyte imbalances may also be present (ASRM 2016; Corbett 2014; Fiedler 2012). Treatment is primarily symptomatic and includes fluid and electrolyte management, analgesics, and prevention of thromboembolic complications (ASRM 2016; SOGC-CFAS 2011). Therapy with gonadotropins should be stopped.

Thromboembolism

In association with and separate from ovarian hyperstimulation syndrome (OHSS), thromboembolic events have been reported. Disease-related concerns:

Porphyria

Gonadotropins may increase the risk of an acute porphyric attack in patients with porphyria or a family history of porphyria; discontinuation of therapy may be necessary with onset or worsening of condition. Special populations:

Elderly

Not indicated for use in females >60 years of age.

Pediatric

Not indicated for use in females Other warnings/precautions:

Appropriate use

To minimize risks, use only at the lowest effective dose. Monitor ovarian response with serum estradiol and vaginal ultrasound on a regular basis.

Experienced physician

These medications should only be used by physicians who are thoroughly familiar with infertility problems and their management.

Multiple births

May result from the use of these medications; advise patients of the potential risk of multiple births before starting the treatment. Discontinuation of therapy is recommended if there is a high risk for multiple pregnancies.

Pregnancy & Lactation

Pregnancy

Use is contraindicated in women who are pregnant. Adverse events have been observed in animal reproduction studies. Ectopic pregnancy, miscarriage, spontaneous abortion, and multiple births have been reported. The incidence of congenital abnormality may be slightly higher after assisted reproductive techniques than with spontaneous conception; higher incidence may be related to parenteral characteristics (maternal age, sperm characteristics). Lutropin alfa is used to stimulate follicular development.

Lactation

Contraindicated

Use in breastfeeding women is contraindicated per the manufacturer labeling. It is not known if lutropin alfa is present into breast milk.

Monitoring

Clinical pearl	Prior to therapy: Baseline LH Monitor sufficient follicular maturation. This may be directly estimated by sonographic visualization of the ovaries and endometrial lining alone or in combination with measurement of serum estradiol levels. The combination of both ultrasonography and measurement of estradiol levels is useful for monitoring for the growth and development of follicles and timing hCG administration. The clinical evaluation of estrogenic activity (changes in vaginal cytology and changes in appearance and volume of cervical mucus) provides an indirect estimate of the estrogenic effect upon the target organs and, therefore, it should only be used adjunctively with more direct estimates of follicular development (ultrasonography and serum estradiol determinations). The clinical confirmation of ovulation is obtained by direct and indirect indices of progesterone production. The indices most generally used are: rise in basal body temperature, increase in serum progesterone, and menstruation following the shift in basal body temperature. Sonographic evidence of ovulation includes collapsed follicle, fluid in the cul-de-sac, ovarian stigmata, and secretory endometrium. Monitor for signs and symptoms of OHSS for at least 2 weeks following hCG administration. OHSS: Monitoring of hospitalized patients should include abdominal circumference, albumin, cardiorespiratory status, electrolytes, fluid balance, hematocrit, hemoglobin, serum creatinine, urine output, urine spe

Clinical pearl

Prior to therapy: Baseline LH Monitor sufficient follicular maturation. This may be directly estimated by sonographic visualization of the ovaries and endometrial lining alone or in combination with measurement of serum estradiol levels. The combination of both ultrasonography and measurement of estradiol levels is useful for monitoring for the growth and development of follicles and timing hCG administration. The clinical evaluation of estrogenic activity (changes in vaginal cytology and changes in appearance and volume of cervical mucus) provides an indirect estimate of the estrogenic effect upon the target organs and, therefore, it should only be used adjunctively with more direct estimates of follicular development (ultrasonography and serum estradiol determinations). The clinical confirmation of ovulation is obtained by direct and indirect indices of progesterone production. The indices most generally used are: rise in basal body temperature, increase in serum progesterone, and menstruation following the shift in basal body temperature. Sonographic evidence of ovulation includes collapsed follicle, fluid in the cul-de-sac, ovarian stigmata, and secretory endometrium. Monitor for signs and symptoms of OHSS for at least 2 weeks following hCG administration. OHSS: Monitoring of hospitalized patients should include abdominal circumference, albumin, cardiorespiratory status, electrolytes, fluid balance, hematocrit, hemoglobin, serum creatinine, urine output, urine spe

Biology & Pharmacokinetics

Pharmacokinetics

Bioavailability	56.0%
Half-life	21.0 h

Registered Products (2)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Luveris	Vial 75 IU	1 vial	THE ARAB DRUG STORE P.S.C	26.030
Pergoveris 150iu/75iu	Vial 75 IU, 150 IU	1 Powder Vial + 1 Solvent Vial	THE ARAB DRUG STORE P.S.C	63.980