Dosing and uses of Menopur, Repronex (menotropins)
Adult dosage forms and strengths
powder for injection: LH/FSH
- 75 IU
Ovulation Induction
Indicated for patients with oligoanovulation
Repronex: 150 IU IM/SC for the first 5 days of treatment; adjustments not to be made more frequently than every 2 days; not to exceed 75-150 IU per adjustment (not to exceed 450 IU/dose); not to exceed 12 days of therapy
If patient's response satisfactory, administer 5000-10,000 units of hCG one day following the last dose of menotropins
Do not administer hCG dose if serum estradiol >2000 pg/mL, if ovaries abnormally large, or abdominal pain occurs; patient should also refrain from intercourse
May repeat therapy if follicular development inadequate or pregnancy does not occur
ART (Assisted Reproductive Technology)
Menopur
- Begin on cycle day 2 or 3
- Initial dose for women who have received a GnRH agonist for pituitary suppression is 225 IU SC qDay
- May be coadministered with urofollitropin (Bravelle), and the total initial dose when the products are combined should not exceed 225 IU (ie, menotropins 150 IU and urofollitropin 75 IU OR menotropins 75 IU and urofollitropin 150 IU)
- Therapy should not exceed 20 days
- Consider adjusting the dose after 5 days based on ovarian response, as determined by ultrasound evaluation of follicular growth and serum estradiol levels
- Do not make additional dosage adjustments more frequently than q2days or by >150 IU at each adjustment
- Continue treatment until adequate follicular development is evident, and then administer hCG Withhold hCG in cases where the ovarian monitoring suggests an increased risk of ovarian hyperstimulation syndrome on the last day of menotropin therapy
- Do not administer daily doses of menotropins or menotropins in combination with urofollitropin that exceed 450 IU
Repronex
- 225 units SC in patients that have received GnRH agonist for pituitary suppression; adjustments not to be made more frequently than every 2 days; not to exceed 75-150 IU per adjustment (not to exceed 450 IU/dose); not to exceed 12 days of therapy
- If patient's response satisfactory, administer 5000-10,000 IU hCG one day following the last dose of menotropins
- Do not administer hCG dose if serum estradiol >2000 pg/mL, if ovaries abnormally large, or abdominal pain occurs; patient should also refrain from intercourse
- May repeat therapy if follicular development inadequate or pregnancy does not occur
Spermatogenesis
75 IU each of LH and FSH SC/IM 3 times/week for at least 4 months
Administration
Reconstitute with 1-2 mL Ns
Use immediately following reconstitution, discard unused portion
Monitor
Females
- Ovarian enlargement (ultrasonography)
- Serum estradiol
Males
- Serum testosterone
- Secondary masculine characteristics
Pediatric dosage forms and strengths
Safety and efficacy not established
Menopur, Repronex (menotropins) adverse (side) effects
>10%
Heachache (34%)
Abdominal pain (18%)
Nausea (12%)
OHSS (13%-dose related)
Injection site pain (4-12%)
1-10%
Flushing (2.4%)
Dizziness (2.6%)
Malaise (2.8%)
Migraine (2.4%)
Breast tenderness (1.8%)
Hot flashes (0.6-2.6%)
Menstrual irregularities (3.2%)
Abdominal cramping/fullness (6%)
Constipation (1.6%)
Diarrhea (2.8%)
Ovarian disease (3.8%)
Vaginal hemorrhage (3.2%)
Back pain (3.2%)
Cough increased (1.6-2.6%)
Respiratory disorder (3.9-5.8%)
Flu-like syndrome (1.3-2.6%)
<1%
Ovarian enlargement & hyperstimulation
Frequency not defined
Arterial thromboembolism (rare but potentially fatal)
Gynecomastia in males
Hemoperitoneum
Warnings
Contraindications
Pregnancy; may cause fetal harm
Hypersensitivity
High levels of FSH indicating primary ovarian failure
Presence of uncontrolled nongonadal endocrinopathies (eg, thyroid, adrenal, or pituitary disorders)
Sex hormone dependent tumors of the reproductive tract and accessory organ
Tumors of pituitary gland or hypothalamus
Abnormal uterine bleeding of undetermined origin
Ovarian cysts or enlargement of undetermined origin, not due to polycystic ovary syndrome
Cautions
Should be administered only by physicians thoroughly experienced in fertility disorders
Hypersensitivity/anaphylactic reactions reported
Ovarian hyperstimulation syndrome (OHSS) reported; OHSS is a medical event distinct from uncomplicated ovarian enlargement and may progress rapidly to become a serious medical event; characterized by dramatic increase in vascular permeability, which can result in a rapid accumulation of fluid in the peritoneal cavity, thorax, and potentially, the pericardium
Use lowest effect dose to minimize abnormal ovarian enlargement; if ovaries are enlarged on last day of therapy, do not administer hCG because of risk for OHSs
May cause pulmonary and vascular complications (eg, atelectasis, ARDS)
Ovarian torsion has been reported after treatment with gonadotropins
Multi-fetal gestation and births have been reported with all gonadotropin therapy
Incidence of congenital malformations after some ART (specifically IVF or ICSI) may be slightly higher than after spontaneous conception (likely due to parental characteristics)
Since infertile women undergoing ART often have tubal abnormalities, the incidence of ectopic pregnancy may be increased
Increased incidence of spontaneous abortion and ovarian neoplasms observed (without causality)
Pregnancy and lactation
Pregnancy category: X
Lactation: Not known whether drug is excreted in breast milk; use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Menopur, Repronex (menotropins)
Mechanism of action
LH & FSH are pituitary gonadotropins that stimulate gonadal function, including spermatogenesis & ovulation
Serum concentration:
Following 6 doses of 150 IU/day SC/IM, serum concentrations of FSH
- SC: 1.7-15.9 mIU/mL
- IM: 0.5-10.1 mIU/mL
LH serum concentrations were 0-3.2 mIU/mL for both routes of administration
Half-Life
Initial phase
- FSH: 4 hr
- LH: 20 min
Final phase
- FSH: 70 hr
- LH: 4 hr
Elimination
Excretion: Urine (8% unchanged)
