Lutropin Alfa

Class: Gonadotropins
Molecular Formula: C437H682N122O134S13
CAS Number: 152923-57-4
Brands: Luveris

Introduction

Gonad-stimulating hormone; a biosynthetic (recombinant DNA origin) form of naturally occurring human LH.1

Uses for Lutropin Alfa

Female Infertility

Used in conjunction with recombinant FSH (follitropin alfa) to stimulate follicular development in anovulatory, infertile women with hypothalamic or pituitary insufficiency (hypogonadotropic hypogonadism)1 2 3 and profound LH deficiency (LH <1.2 international units [IU]/L).1 7

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Lutropin Alfa Dosage and Administration

General

  • Should be prescribed by clinicians experienced in infertility treatment.1

  • Prior to initiating therapy with lutropin alfa, perform a thorough gynecologic and endocrinologic evaluation; assess pelvic anatomy and rule out early pregnancy.1 Determine that serum LH concentrations are <1.2 IU/L, FSH concentrations <5 IU/L, and a negative progestin challenge test (i.e., a lack of withdrawal bleeding with progesterone administration).1 2 3 5 8 Perform a thorough diagnostic evaluation in patients who demonstrate abnormal uterine bleeding and other signs of endometrial abnormalities.1 8 Evaluate partner’s infertility.1 8

  • Administer lutropin alfa in conjunction with recombinant follitropin alfa daily until follicular maturation (as determined by serum estradiol concentrations and ovary ultrasound examinations) occurs.1

  • When ultrasound assessment and serum estradiol concentrations show sufficient follicular maturation, discontinue lutropin alfa and follitropin alfa; administer hCG 1 day after the last dose of lutropin alfa and follitropin alfa to complete final follicular maturation and induce ovulation.1

  • Do not administer hCG if the ovaries show an excessive response to treatment with gonadotropins because of an increased risk of ovarian hyperstimulation syndrome.1 (See Ovarian Hyperstimulation Syndrome under Cautions.)

  • Encourage couple to have daily sexual intercourse beginning the day prior to administration of hCG, until ovulation occurs (as determined by a rise in basal body temperature, an increase in serum progesterone, and menstruation following a shift in basal body temperature).1 (See Adequate Patient Evaluation and Monitoring under Cautions.)

  • Safety and efficacy of concomitant administration of lutropin alfa and other recombinant or urinary human follicle-stimulating hormone (FSH) preparations unknown.1 7 8

Administration

Sub-Q Administration

Administer by sub-Q injection, generally into the abdomen;1 may be self-administered by patient.1 2

Administer lutropin alfa and follitropin alfa as separate injections.1

Reconstitution

Reconstitute vial containing 82.5 units of lutropin alfa sterile lyophilized powder with 1 mL of sterile water for injection (provided by manufacturer).1

Gently swirl vial until lyophilized powder dissolves; do not shake.1 Following reconstitution, total extractable amount per 82.5 unit vial is 75 units.1

Administer immediately following reconstitution.1 7 8

Dosage

Dosage of lutropin alfa is expressed in terms of international units (IU, units) of LH activity.1

Adults

Female Infertility
Sub-Q

75 units daily in conjunction with follitropin alfa (75–150 units daily) until follicular maturation occurs.1 (See General under Dosage and Administration.)

If stimulation of ovulation is unsuccessful, individualize dosage of lutropin alfa and follitropin alfa administered in subsequent cycles based on woman’s response in the preceding cycle.1 2

Prescribing Limits

Adults

Female Infertility
Subcutaneous

Maximum 225 units daily studied in clinical trials.2 3 7

Maximum 14 days of therapy recommended unless signs of imminent follicular development (e.g., follicle size exceeding 10 mm) are present at 14 days.1 2 3

Maximum 3 cycles of therapy administered in clinical trials.2 3

Cautions for Lutropin Alfa

Contraindications

  • Known hypersensitivity to lutropin alfa, other LH preparations, or any ingredient in the formulation.1 8

  • Primary ovarian failure.1 8

  • Uncontrolled thyroid or adrenal dysfunction.1 8

  • Uncontrolled organic intracranial lesions (e.g., pituitary neoplasms).1 8

  • Abnormal intrauterine bleeding of undetermined origin.1 8

  • Ovarian cysts or enlargement of undetermined origin.1 8

  • Sex-hormone-dependent neoplasms of the reproductive tract and accessory organs.1 8

  • Known or suspected pregnancy.1 8

Warnings/Precautions

Warnings

Ovarian Enlargement

Risk of mild to moderate uncomplicated ovarian enlargement; may be accompanied by abdominal distension and/or pain but generally regresses without treatment within 2–3 weeks.1 Careful monitoring of ovarian response recommended.1

If ovaries are abnormally enlarged (i.e., development of ≥3 follicles with a mean diameter of ≥15 mm) and/or if excessive estradiol production (>1100 pg/mL) occurs following the last dose of lutropin alfa and follitropin alfa, withhold hCG administration during the current course of therapy to minimize the risk of development of ovarian hyperstimulation syndrome (OHSS).1 (See Ovarian Hyperstimulation Syndrome under Cautions.)

Ovarian Hyperstimulation Syndrome (OHSS)

Risk of potentially severe OHSS, characterized by an apparent dramatic increase in vascular permeability that may result in rapid accumulation of fluid in the peritoneal cavity, thorax, and potentially, the pericardium.1

OHSS may progress rapidly (within 24 hours to several days) and is initially manifested by severe pelvic pain, nausea, vomiting, and weight gain.1 Other symptoms include abdominal pain/distension, diarrhea, dyspnea, and oliguria.1 Hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic events may occur.1

Transient liver function test abnormalities, which may be accompanied by morphologic changes (as detected by liver biopsy) have been reported.1

OHSS occurs most often after completion of gonadotropin therapy; develops rapidly, reaching maximum severity after 7–10 days; and usually resolves spontaneously with the onset of menses.1 OHSS may be more severe and protracted if pregnancy occurs.1

Discontinue therapy with lutropin alfa and follitropin alfa if ovaries are abnormally enlarged or abdominal pain occurs; withhold hCG administration and advise patient to avoid sexual intercourse.1

If severe OHSS occurs, discontinue therapy, hospitalize patient, and consult a clinician experienced in the management of OHSS or fluid and electrolyte imbalances.1

Multiple Births

Multiple ovulations resulting in multiple gestations reported.1 3 6 8

Pulmonary and Vascular Complications

Potential for arterial thromboembolism exists.1

General Precautions

Adequate Patient Evaluation and Monitoring

Administer only under the supervision of qualified clinicians experienced in fertility disorders and in interpretation of indices of ovulation.1

Monitor follicular development (e.g., using ovarian ultrasound, serum estradiol concentrations) in order to correctly identify follicular maturation, determine timing of hCG administration, detect ovarian enlargement, and minimize risks of OHSS and multiple gestation.1

Obtain clinical confirmation of ovulation from direct and indirect indices of progesterone production, including a rise in basal body temperature, increase in serum progesterone, and menstruation following a shift in basal body temperature.1 Sonographic evidence of ovulation includes findings of fluid in the cul-de-sac, ovarian stigmata, collapsed follicle, and a secretory endometrium.1

Specific Populations

Pregnancy

Category X.1 (See Contraindications under Cautions.)

Lactation

Not known whether lutropin alfa is distributed into milk.1 Use not recommended.1

Pediatric Use

Safety and efficacy not established.1 Not indicated for use in pediatric patients.1

Geriatric Use

Safety and efficacy not established.1 Not indicated for use in geriatric patients.1

Hepatic Impairment

Pharmacokinetics not evaluated.1

Renal Impairment

Pharmacokinetics not evaluated.1

Common Adverse Effects

Headache,1 2 3 nausea,1 2 3 ovarian hyperstimulation,1 3 breast pain,1 abdominal pain,1 ovarian cyst.1

Interactions for Lutropin Alfa

No formal drug interaction studies to date.1

Lutropin Alfa Pharmacokinetics

Absorption

Bioavailability

Mean absolute bioavailability is 56%.1

Onset

Following sub-Q administration, maximum serum concentrations reached after 4–16 hours.1

Elimination

Metabolism

<5% of dose excreted renally as unchanged drug.1

Half-life

Biphasic; terminal half-life is approximately 18 hours.1

Stability

Storage

Parenteral

Injection

Store refrigerated or at room temperature (2–25°C); protect from light.1

Use immediately after reconstitution; discard unused portion.1

Actions

  • Stimulates (in combination with FSH) the development of a potentially competent follicle to indirectly prepare the reproductive tract for implantation and pregnancy.1

  • Stimulates theca cells in the ovaries to secrete androgens; increases estradiol secretion by the follicles.1 4

  • Substitutes for the endogenous LH surge responsible for ovulation and stimulates late maturation of the ovarian follicle, resumption of oocytic meiosis, initiation of rupture of the preovulatory ovarian follicle, and oocyte expulsion. 1 4

  • Induces and maintains the corpus luteum.4

Advice to Patients

  • Importance of providing patient a copy of manufacturer’s patient information.1

  • Importance of patient understanding and following instructions regarding reconstitution of lutropin alfa, duration of treatment, and required monitoring procedures.1

  • Importance of informing patient of potential adverse effects (e.g., ovarian hyperstimulation syndrome, multiple gestation).1

  • Importance of patients informing a clinician if severe pain or bloating in the stomach or pelvic area, severe upset stomach, vomiting, or weight gain occurs.8

  • Importance of patients contacting a clinician immediately if a dose of lutropin alfa is missed.8

  • Importance of patient informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1 8

  • Importance of women informing their clinician if they plan to breast-feed.1

  • Importance of informing patient of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Lutropin Alfa

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for subcutaneous use only

82.5 units (delivers 75 units)

Luveris

Serono

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Serono. Luveris (lutropin alfa) for injection prescribing information. Rockland, MA; 2005 May.

2. European Recombinant Human LH Study Group. Recombinant human luteinizing hormone (LH) to support recombinant human follicle-stimulating hormone (FSH)-induced follicular development in LH- and FSH-deficient anovulatory women: a dose-finding study. J Clin Endorinol Metab. 1998; 83:1507-14.

3. Burgues S and the Spanish Collaborative Group on Female Hypogonadotrophic Hypogonadism. The effectiveness and safety of recombinant human LH to support follicular development induced by recombinant human FSH in WHO group I anovulation: evidence from a multicentre study in Spain. Hum Reprod. 2001; 16:2525-32. [PubMed 11726569]

4. le Contonnec JY, Porchet HC, Beltrami V et al. Clinical pharmacology of recombinant human luteinizing hormone: part I. Pharmacokinetics after intravenous administration to healthy female volunteers and comparison with urinary human luteinizing hormone. Fertil Steril. 1998; 69:189-94. [PubMed 9496327]

5. Kingingham RB, Apgar BS, Schwenk TL et al. Evaluation of amenorrhea. Am Fam Physician. 1996;53:1185-94.

6. Campo S, Campo V, Lanzone A. Twin pregnancy using recombinant gonadotropins in a woman with hypogondotropic hypogonadism. Gynecol Endocrinol. 2002; 16:27-32. [PubMed 11915578]

7. Serono, Rockland, MA: Personal communication.

8. Serono. Luveris (lutropin alfa) injection FAQ’s. Rockland, MA. Undated. Available at . Accessed 2006 Dec 1.

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