Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injection, powder for reconstitution:
Menopur: 75 units [supplied with diluent]
Pharmacology
Mechanism of Action
Menotropins is a purified combination of follicle stimulating hormone (FSH) and luteinizing hormone (LH) extracted from the urine of postmenopausal women. Treatment provides ovarian follicular growth and maturation in females who do not have primary ovarian failure. Also stimulates spermatogenesis in males (off-label use)
Pharmacokinetics/Pharmacodynamics
Excretion
Urine.
Time to Peak
FSH (following a single dose): 18 hours (SubQ).
Half-Life Elimination
Follicle-stimulating hormone (FSH) 11 to 13 hours (following multiple doses).
Use: Labeled Indications
For multiple follicle development and pregnancy in ovulatory women as part of an assisted reproductive technology cycle.
Limitations of use: Prior to therapy, preform a complete gynecologic exam and endocrinologic evaluation to diagnose the cause of infertility; exclude the possibility of pregnancy; evaluate the fertility status of the male partner; exclude a diagnosis of primary ovarian failure.
Use: Off Label
Stimulation of spermatogenesisyes
Based on the American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients, menotropins given for stimulation of spermatogenesis in males with primary or secondary hypogonadotropic hypogonadism is effective and recommended in the management of this condition.
Contraindications
Hypersensitivity to menotropins or any component of the formulation; primary ovarian failure as indicated by a high follicle-stimulating hormone level; uncontrolled nongonadal endocrinopathies (eg, thyroid, adrenal, pituitary); pituitary or hypothalamic tumors; sex hormone-dependent tumors of the reproductive tract and accessory organs; abnormal uterine bleeding of undetermined origin; ovarian cyst or enlargement not due to polycystic ovary syndrome; pregnancy.
Dosage and Administration
Dosing: Adult
Assisted reproductive technologies (females): SubQ: Initial: 225 units once daily beginning on cycle day 2 or 3; Menotropins may be administered together with urofollitropin and the total initial dose of both products combined should not exceed 225 units (menotropins 150 units and urofollitropin 75 units; or menotropins 75 units and urofollitropin 150 units). Adjust dose after 5 days based on ultrasound monitoring of ovarian response and/or measurement of serum estradiol levels. Do not make additional adjustments more frequently than once every 2 days or by >150 units. Maximum daily dose: 450 units (of menotropins, or menotropins plus urofollitropin); treatment >20 days is not recommended. Once follicular growth indicates an adequate ovarian response, administer hCG. Follow current clinical practice to reduce the risk of ovarian hyperstimulation syndrome.
Spermatogenesis (males) (off-label use): IM: Following pretreatment with hCG: 75 units 3 times per week with hCG twice weekly until sperm is detected in the ejaculate (4 to 6 months); if response is inadequate after 6 months, may increase menotropins dosage to 150 units 3 times per week for another 6 months (AACE [Petak 2002]).
Reconstitution
Reconstitute with sodium chloride 0.9% for injection (provided); gently swirl to dissolve, do not shake to avoid formation of bubbles. Use immediately after reconstitution. May also be mixed with Bravelle (urofollitropin for injection).
If >1 vial of menotropins is required for a single dose, up to 6 vials can be reconstituted and administered as a single injection. This is done by first reconstituting 1 vial with sodium chloride 0.9% injection as previously described, withdrawing the entire contents of the reconstituted vial, and (using this as the diluent for the second vial) injecting into the second vial, etc. Use immediately after reconstitution.
After reconstitution inject immediately; discard any unused portion.
Administration
SubQ: Administer to alternating sites of the lower abdomen.
Storage
Store at 3°C to 25°C (37°F to 77°F). Protect from light.
Drug Interactions
There are no known significant interactions.
Adverse Reactions
Adverse effects and incidences may vary according to specific product, indication, dosage, or route of administration.
>10%: Genitourinary: Multiple gestation (35%)
1% to 10%:
Central nervous system: Headache (5% to 6%)
Endocrine & metabolic: Ovarian disease (3% to 8%), ovarian hyperstimulation syndrome (2% to 7%)
Gastrointestinal: Abdominal pain (5% to 7%), nausea (4% to 7%), abdominal cramps (3% to 7%), enlargement of abdomen (2% to 6%), gastrointestinal fullness (≥5%), vomiting (3%), diarrhea (2%)
Genitourinary: Vaginal hemorrhage (3% to 8%), pelvic pain (1% to 3%), breast tenderness (2%), ectopic pregnancy (1%)
Infection: Infection (1%)
Local: Injection site reaction (2% to 8%), swelling at injection site (1% to 8%), pain at injection site (≤4%), inflammation at injection site (2%)
Respiratory: Dyspnea (1% to 2%)
Frequency not defined:
Cardiovascular: Tachycardia
Central nervous system: Dizziness
Dermatologic: Rash at injection site, skin rash
Endocrine & metabolic: Ovarian cyst, ovary enlargement
Hematologic & oncologic: Hemoperitoneum, ovarian neoplasm
Hypersensitivity: Anaphylaxis
Local: Irritation at injection site
Respiratory: Flu-like symptoms, tachypnea
Miscellaneous: Fetal abnormality, ovarian torsion
<1%, postmarketing, and/or case reports: Abdominal distention, abdominal distress, acne vulgaris, acute respiratory distress syndrome, angioedema, atelectasis, cerebrovascular accident, embolism, facial edema, fatigue, hot flash, hypersensitivity reaction, laryngeal edema, local tissue necrosis, lower abdominal pain, malaise, occlusion of cerebral arteries, occlusive arterial disease (may result in loss of limb), pulmonary complications, pulmonary embolism, pulmonary infarct, thromboembolism, thrombophlebitis (includes venous), thrombosis
Warnings/Precautions
Concerns related to adverse effects:
- Hypersensitivity: Hypersensitivity and anaphylactic reactions have been reported; discontinue use for serious reactions and treat appropriately.
- Ovarian enlargement: The lowest effective dose should be used to decrease the risk of abnormal ovarian enlargement. If ovaries are abnormally enlarged on the last day of menotropin treatment, follow current clinical practice to reduce the risk of ovarian hyperstimulation syndrome (OHSS).
- 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 hCG treatment but may become most severe 7 to 10 days after therapy (Corbett 2014). Mild/moderate OHSS signs/symptoms may include abdominal distention/discomfort, diarrhea, nausea, vomiting, and mild/moderate enlargement of ovaries/ovarian cysts. Severe OHSS signs/symptoms may include severe abdominal pain, anuria/oliguria, ascites, severe dyspnea, hypotension, hydrothorax, nausea/vomiting (intractable), pleural effusion, rapid weight gain, venous thrombosis, and large ovarian cysts. 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; Shmorgun 2017).
- Ovarian torsion: Has been reported following gonadotropin treatment; may be related to OHSS, prior ovarian torsion, prior or current ovarian cyst, polycystic ovaries, pregnancy, or prior abdominal surgery. Early diagnosis and prompt detorsion may limit the extent of ovarian damage.
- Pulmonary effects: Serious pulmonary conditions (atelectasis, acute respiratory distress syndrome, and exacerbation of asthma) have been reported.
- Thromboembolism: In association with and separate from OHSS, thromboembolic events have been reported. Risk may be increased in patients with a personal or family history of thromboembolic events, severe obesity, or thrombophilia.
Other warnings/precautions:
- Appropriate use: To minimize risks, use only at the lowest effective dose. Monitor ovarian response with transvaginal ultrasound; concurrent measurement of estradiol levels may also be useful.
- 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 multi-fetal gestation and multiple births before starting the treatment.
Monitoring Parameters
Monitor follicular growth by transvaginal ultrasound to determine adequate ovarian response and timing of hCG administration. Concurrent measurement of estradiol levels may also be useful.
Monitor for signs and symptoms of ovarian hyperstimulation syndrome (OHSS) for at least 2 weeks following hCG administration. Initial symptoms of moderate to severe OHSS may include a sensation of bloating, abdominal pain, rapid weight gain, and decreased urine output (Shmorgun 2017).
OHSS: Monitoring of hospitalized patients should include albumin, degree of ascites, cardiorespiratory status, electrolytes, fluid balance, hematocrit, hemoglobin, hydration, serum creatinine, urine output, urine specific gravity, signs of thromboembolism, vital signs, weight (daily or as necessary) and liver enzymes (weekly) (Shmorgun 2017).
Males: Monitor for sufficient spermatogenesis (AACE [Petak 2002]).
Pregnancy
Pregnancy Risk Factor
X
Pregnancy Considerations
Ectopic pregnancy, congenital abnormalities, spontaneous abortion, and multi-fetal gestations/births have been reported. The incidence of congenital abnormality may be slightly higher after assisted reproductive technology (ART) than with spontaneous conception; higher incidence may be related to parenteral characteristics (maternal age, genetics, sperm characteristics). Menotropins are used for the induction of ovulation and with ART; use is contraindicated in women who are already pregnant. Pregnancy should be excluded prior to treatment.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience injection site irritation, nausea, abdominal pain, headache, abdominal cramps, or bloating. Have patient report immediately to prescriber breast pain, enlarged breasts, fast heartbeat, yellow skin, fast breathing, pale skin, blue/gray skin discoloration, flu-like symptoms, signs of ovarian hyperstimulation syndrome (severe abdominal pain or bloating; severe nausea, vomiting, or diarrhea; excessive weight gain; shortness of breath; or change in amount of urine passed), or signs of blood clots (numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
