Menopur

Gonadotropins
Pituitary Hormones

NOTE: Menotropins (hMG) should be used only by health care prescribers who are experienced in managing endocrine or fertility disorders and only in facilities where appropriate clinical and endocrinology evaluations are available.
Hazardous Drugs Classification
NIOSH 2016 List: Group 3
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.

The following menotropins products are administered by intramuscular (IM) injection only: Humegon, Pergonal.
Repronex may be administered by either intramuscular (IM) or subcutaneous (SC) injection.
Menopur is administered by subcutaneous (SC) injection.
Do not inject any menotropins product intravenously.
 
Reconstitution of either IM or SC injections:
Reconstitute dose with 1—2 ml of 0.9% Sodium Chloride Injection, USP (NS injection), as instructed and provided by the manufacturer for the particular product used. For example, for patients requiring a single injection from multiple vials of Menopur for their dose, up to 6 vials can be reconstituted with just 1 ml of NS Injection, using the technique described by the manufacturer.
Use reconstituted injections immediately and discard any unused portions.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Draw the reconstituted injection into an empty, sterile syringe before administration.

Intramuscular injection (Humegon, Pergonal, or Repronex):
Adults: Inject deeply into a large muscle, preferably into the anterolateral aspect of the thigh.

Subcutaneous injection (Repronex):
Subcutaneous injections of Repronex should be made into the lower abdomen.
Inject subcutaneously taking care not to inject intradermally.
Alternate sides with each dose administration.
 
Subcutaneous injection (Menopur):
When administered via subcutaneous injection, Menopur and Bravelle (urofollitropin) may be mixed and administered in the same syringe.
Subcutaneous injections of Menopur should be made into the lower abdomen. Injection into the thigh is not recommended unless the lower abdomen is not usable because of scarring, surgical deformity or other medical conditions.
Inject subcutaneously taking care not to inject intradermally.
Alternate sides with each dose administration.

ovarian hyperstimulation syndrome / Delayed / 2.0-13.2
angioedema / Rapid / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
thromboembolism / Delayed / 0-1.0
stroke / Early / 0-1.0
pulmonary embolism / Delayed / 0-1.0
thrombosis / Delayed / Incidence not known
acute respiratory distress syndrome (ARDS) / Early / Incidence not known

ovarian enlargement / Delayed / 5.0-10.0
vaginal bleeding / Delayed / 3.1-7.9
hot flashes / Early / 0.6-2.6
migraine / Early / 2.4-2.4
dyspnea / Early / 1.0-2.1
constipation / Delayed / 0-1.6
phlebitis / Rapid / 0-1.0
erythema / Early / Incidence not known
tachypnea / Early / Incidence not known
sinus tachycardia / Rapid / Incidence not known

headache / Early / 5.2-34.1
gynecomastia / Delayed / 0-30.0
abdominal pain / Early / 5.0-17.6
nausea / Early / 4.0-12.0
injection site reaction / Rapid / 1.0-11.8
vomiting / Early / 0-4.2
pelvic pain / Delayed / 0.4-3.9
back pain / Delayed / 0-3.2
diarrhea / Early / 0-2.8
malaise / Early / 2.6-2.8
dizziness / Early / 2.6-2.6
mastalgia / Delayed / 1.8-2.6
cough / Delayed / 1.6-2.6
flushing / Rapid / 2.4-2.4
urticaria / Rapid / 0-1.0
rash / Early / 0-1.0
fatigue / Early / Incidence not known
fever / Early / Incidence not known
pruritus / Rapid / Incidence not known

Menopur

Rx

Purified preparation of FSH and LH, obtained from the urine of postmenopausal women; also referred to as HMG; used for ovulation induction and associated with multiparity; also used for oligospermia in males in combination with hCG; highly purified products are of similar efficacy in IVF to recombinant FSH and produce less injection reactions than less purified menotropins products.

75 international units of FSH/LH activity given IM once daily for 7 to 12 days as indicated by patient response, followed by hCG 1 day after the last dose of menotropins. If there is indication of ovulation but no pregnancy, the dose of menotropins in the cycle may be increased after 2 more cycles to 150 international units of FSH/LH activity. In general, more than 150 international units/day of FSH/LH activity is not recommended. Occasionally, the chosen daily dose of menotropins may be administered in 2 divided daily doses. Dosing beyond 12 days in any 1 cycle is not recommended.

75 international units of FSH/LH activity given IM or subcutaneously once daily for the first 5 days. Based on clinical monitoring, subsequent dosing may be adjusted according to patient response. Adjust dose by no more than 75 to 150 IU/day every 2 days. Occasionally, the daily dose may be administered in 2 divided doses. Max dose: 450 international units/day; duration beyond 12 days in any cycle is not recommended. Discontinue when the patient response is appropriate. Give hCG 1 day after the last dose of Repronex.

75 to 150 international units of FSH/LH activity given IM once daily for 7 to 12 days. The 75 international unit dose is recommended initially. The daily dose may be administered in 2 divided doses. Max dose: generally 150 international units/day; duration beyond 12 days in any cycle is not recommended. Discontinue when the patient response is appropriate. Give hCG 1 day after the last dose of menotropins. Oocyte retrieval is usually performed 34 to 36 hours later, before ovulation can occur.

225 international units of FSH/LH activity given IM or subcutaneously once daily initially. Based on clinical monitoring, subsequent dosing may be adjusted according to patient response. Adjust dose by no more than 75 to 150 international units/day every 2 days. The daily dose may be administered in 2 divided doses. Max dose: 450 international units/day; duration beyond 12 days in any cycle is not recommended. Discontinue when the patient response is appropriate. Give hCG 1 day after the last dose of Repronex. Oocyte retrieval is usually performed 34 to 36 hours later, before ovulation can occur.

225 international units of FSH/LH activity given subcutaneously once daily initially. Urofollitropin (Bravelle) may be administered together with menotropins (Menopur) with a total initial dose not to exceed 225 international units subcutaneously (150 international units urofollitropin, 75 international units menotropins OR 75 international units urofollitropin, 150 international units menotropins). Based on clinical monitoring, subsequent dosing may be adjusted according to patient response. Adjust dose by no more than 150 international units/day every 2 days. Max dose: 450 international units/day (menotropins alone or in combination with urofollitropin); duration beyond 20 days in any cycle is not recommended. Discontinue when the patient response is appropriate. Give hCG 1 day after the last dose of Menopur. Oocyte retrieval is usually performed 34 to 36 hours later, before ovulation can occur.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

There are no drug interactions associated with Menotropins products.

Menopur Subcutaneous Inj Pwd F/Sol: 75-75IU

No specific maximum dosage limit recommendations are available. Dosage regimens of menotropins depend upon the patient's age, sex, condition being treated, and the prescribing clinician's judgment. Therefore, doses vary widely and must be carefully individualized.

Mechanism of Action: Since menotropins are purified preparations of human FSH and LH, the mechanism of action mimics that of the two gonadotropins. However, the FSH activity of menotropins is dramatically greater than that of the LH in the preparation. A small amount of hCG is also present in the preparations. Endogenous FSH and LH are normally secreted from the pituitary every hour in both males and females, and the patterns of secretion are both age and sex dependent. Both FSH and LH are involved in the regulation of ovarian and testicular function.•Activity in adult females: Endogenous FSH is normally released in abundance during the follicular phase of the menstrual cycle. FSH stimulates the ovarian follicle and controls estrogen release from the granulosa cells of the ovary. Endogenous LH is normally released in a pulsatile fashion in the follicular phase, and then produces an LH surge just before ovulation to promote the final maturation of the oocyte ans corpus luteum. The LH surge stimulates the luteal cells (corpus luteum) to produce progesterone and the thecal cells to produce androgens. Most of the androgens produced are converted to estradiol and other estrogens. In fertility protocols, menotropins are primarily administered to mimic the action of FSH, and administration usually results in follicular growth and maturation. In some circumstances, menotropins therapy is proceeded by or concurrent with GnRH agonists or antagonists to place pituitary hormone regulation in the control of the fertility specialist. To produce ovulation, human chorionic gonadotropin (hCG), which has essentially identical actions as those of LH, is administered after menotropins. Following hCG administration, final luteinization or maturation of the oocytes occurs and either ovulation can ensue, or oocyte retrieval can take place for assisted reproductive technology (ART) procedures such as in vitro fertilization (IVF).•Activity in adult and adolescent males: Endogenous FSH, along with testosterone, normally stimulates spermatogenesis and androgen-binding protein synthesis in the Sertoli cells of the seminiferous tubules. Endogenous LH stimulates testosterone production in the Leydig cells of the testes. Menotropins, whose primary activity is to provide FSH, are combined with hCG (which acts like LH to stimulate testosterone production) to stimulate spermatogenesis and an increase in testicular volume. Pre-treatment with hCG is required to increase the production of testosterone and the development of secondary sex characteristics prior to the coadministration of menotropins. Once initiated, it takes 70—80 days for germ cells to reach the spermatozoal stage; several months of combination treatment are usually required until adequate sperm counts are produced.

Menotropins are administered parenterally either as intramuscular (IM) injections, or for select products, as subcutaneous (SC) injections. Due to their polypeptide nature, gonadotropins are quickly destroyed in the gastrointestinal tract. The exact distribution and metabolism of menotropins have not been elucidated. Based on the kinetics of endogenous gonadotropins, the terminal half-life of LH is roughly 0.5—4 hours. 

Based on the ratio of FSH maximum concentrations and the area-under-the-curve, SC administration of menotropins is not bioequivalent to IM administration. Compared to IM administration, SC administration increases the Cmax and AUC of FSH by 35% and 20% respectively. The median time to reach peak FSH concentrations is 18 hours for IM dosing. Following repeated IM administration of menotropins, the pharmacokinetics of serum FSH concentrations are linear up to a dose of 450 IU/day; serum LH concentrations are low and variable. The mean elimination half-life of FSH is 59.2 hours following single dose IM administration.

Based on the ratio of FSH maximum concentrations and the area-under-the-curve, SC administration of menotropins is not bioequivalent to IM administration. Compared to IM administration, SC administration increases the Cmax and AUC of FSH by 35% and 20% respectively. The median time to reach peak FSH concentrations is 12 hours for SC dosing. The mean elimination half-life of FSH is 53.7 hours following single dose SC administration.

Menotropins are used in the treatment of infertility and are classified in FDA pregnancy category X and thus are contraindicated after conception has occurred. Limited data are available regarding the use of menotropins in human gestation, and the potential for serious fetal harm cannot be excluded. Therefore, pregnancy should be ruled out prior to the administration of menotropins with each fertility treatment course. In addition to potential effects on the fetus, including congenital malformation, protocols using menotropins inherently increase the risk of multiple gestation and the risks associated with such pregnancies. The rate of spontaneous abortions in women who become pregnant after receiving menotropins may be increased; reasons have not been established.

Menotropins should be used with caution in lactating mothers who are breast-feeding their infants. Most endogenous gonadotropins are found in breast milk or tissues to some degree. It is neither known whether exogenous menotropins are distributed into breast milk, nor what effect they would have on the feeding infant.