Luveris 75

/ Merck

Posology: In LH and FSH deficient women, the objective of Luveris therapy in association with FSH is to develop a single mature Graafian follicle from which the oocyte will be liberated after the administration of human chorionic gonadotropin (hCG). Luveris should be given as a course of daily injections simultaneously with FSH. Since these patients are amenorrhoeic and have
low endogenous oestrogen secretion, treatment can commence at any time.
Luveris should be administered concomitantly with follitropin alfa.
Treatment should be tailored to the individual patient’s response as assessed by measuring follicle size by ultrasound and oestrogen response. A recommended regimen commences at 75 IU of lutropin alfa (ie. one vial of Luveris) daily with 75-150 IU FSH.
In clinical trials, Luveris has been shown to increase the ovarian sensitivity to follitropin alfa.
If an FSH dose increase is deemed appropriate, dose adaptation should preferably be after 7-14 day intervals and preferably by 37.5 IU-75 IU increments. It may be acceptable to extend the duration of stimulation in any one cycle to up to 5 weeks.
When an optimal response is obtained, a single injection of 250 micrograms of r-hCG or 5,000 IU to 10,000 IU hCG should be administered 24-48 hours after the last Luveris and FSH injections. The patient is recommended to have coitus on the day of, and on the day following, hCG administration.
Alternatively, intrauterine insemination (IUI) may be performed.
Luteal phase support may be considered since lack of substances with luteotrophic activity (LH/hCG) after ovulation may lead to premature failure of the corpus luteum.
If an excessive response is obtained, treatment should be stopped and hCG withheld.
Treatment should recommence in the next cycle at a dose of FSH lower than that of the previous cycle.
Special populations:
Older people: There is no relevant indication for the use of Luveris in the elderly population. Safety and effectiveness of Luveris in elderly patients have not been established.
Renal or hepatic impairment: Safety, efficacy, and pharmacokinetics of Luveris in patients with renal or hepatic impairment have not been established.
Paediatric population: There is no relevant indication for the use of Luveris in the paediatric population.
Method of administration: Luveris is intended for subcutaneous use. The first injection of Luveris should be performed under direct medical supervision. The powder should be reconstituted, immediately prior to use, with the solvent provided. Self-administration of this medicinal product should only be
performed by patients who are well-motivated, adequately trained and with access to expert advice.

In association with a follicile stimulating hormone (FSH), the preparation is recommended for the stimulation of follicular development in women with severe LH and FSH deficiency. In clinical trials those patients were defined by endogenous serum LH level < 1.2 IU/L.

– hypersensitivity to active substances or to any of the excipients.
– tumours of the hypothalamus and pituitary gland
– ovarian enlargement or ovarian cyst unrelated to polycystic ovarian disease and of unknown origin
– gynaecological haemorrhages of unknown origin
– ovarian, uterine, or mammary carcinoma
Luveris must not be used when a condition exists which would make a normal pregnancy impossible, such as:
– primary ovarian failure
– malformations of sexual organs incompatible with pregnancy
– fibroid tumours of the uterus incompatible with pregnancy

Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
General recommendations: Before starting treatment, the couple’s infertility should be assessed as appropriate and putative contraindications for pregnancy evaluated. In addition, patients should be evaluated for hypothyroidism, adrenocortical deficiency and hyperprolactinemia and appropriate specific treatment given.
Porphyria: In patients with porphyria or a family history of porphyria, this medicinal product may increase the risk of an acute attack. Deterioration or a first appearance of this condition may require cessation of treatment.
Ovarian hyperstimulation syndrome (OHSS): A certain degree of ovarian enlargement is an expected effect of controlled ovarian stimulation. It is more commonly seen in women with polycystic ovarian syndrome and usually regresses without treatment.
In distinction to uncomplicated ovarian enlargement, OHSS is a condition that can manifest itself with increasing degrees of severity. It comprises marked ovarian enlargement, high serum sex steroids, and an increase in vascular permeability which can result in an accumulation of fluid in the peritoneal, pleural and, rarely, in the pericardial cavities.
Mild manifestations of OHSS may include abdominal pain, abdominal discomfort and distension, or enlarged ovaries. Moderate OHSS may additionally present with nausea, vomiting, ultrasound evidence of ascites or marked ovarian enlargement.
Severe OHSS further includes symptoms such as severe ovarian enlargement, weight gain, dyspnoea or oliguria. Clinical evaluation may reveal signs such as hypovolaemia, haemoconcentration, electrolyte imbalances, ascites, pleural effusions, or acute pulmonary distress. Very rarely, severe OHSS may be complicated by ovarian torsion or thromboembolic events, such as pulmonary embolism, ischaemic stroke or myocardial infarction.
Independent risk factors for developing OHSS include young age, lean body mass, polycystic ovarian syndrome, higher doses of exogenous gonadotropins, high absolute or rapidly rising serum estradiol levels and previous episodes of OHSS, large number of developing ovarian follicles and large number of oocytes retrieved in assisted reproductive technology (ART) cycles.
Adherence to recommended drug and FSH dosage and regimen of administration can minimise the risk of ovarian hyperstimulation. Monitoring of stimulation cycles by ultrasound scans as well as estradiol measurements are recommended to early identify risk factors.
There is evidence to suggest that hCG plays a key role in triggering OHSS and that the syndrome may be more severe and more protracted if pregnancy occurs. Therefore, if signs of ovarian hyperstimulation occur, it is recommended that hCG be withheld and the patient be advised to refrain from coitus or use barrier contraceptive methods for at least 4 days. As OHSS may progress rapidly (within 24 hours) or over several days to become a serious medical event, patients should be followed for at least two weeks after hCG administration.
Mild or moderate OHSS usually resolves spontaneously. If severe OHSS occurs, it is recommended that gonadotropin treatment be stopped if still ongoing and that the patient be hospitalised and appropriate therapy be started.
Ovarian torsion: Ovarian torsion has been reported after treatment with other gonadotropins. This may be associated with other risk factors such as OHSS, pregnancy, previous abdominal surgery, past history of ovarian torsion, previous or current ovarian cyst and polycystic ovarian syndrome. Damage to the ovary due to reduced blood supply can be limited by early diagnosis and immediate detorsion.
Multiple pregnancy: In patients undergoing induction of ovulation, the incidence of multiple pregnancy and births is increased compared with natural conception. The majority of multiple conceptions are twins. Multiple pregnancy, especially high order, carry an increased risk of adverse maternal and perinatal outcomes.
To minimise the risk of higher order multiple pregnancy, careful monitoring of ovarian response is recommended. In patients undergoing ART procedures the risk of multiple pregnancy is related mainly to the number of embryos replaced, their quality and the patient age.
Pregnancy loss: The incidence of pregnancy loss by miscarriage or abortion is higher in patients undergoing stimulation of follicular growth for ovulation induction or ART than following natural conception.
Ectopic pregnancy: Women with a history of tubal disease are at risk of ectopic pregnancy, whether the pregnancy is obtained by spontaneous conception or with fertility treatments. The prevalence of ectopic pregnancy after ART was reported to be higher than in the general population.
Congenital malformations: The prevalence of congenital malformations after ART may be slightly higher than after spontaneous conceptions. This could be due to parental factors (e.g. maternal age, genetics), ART procedures and multiple pregnancies.
Thromboembolic events: In women with recent or ongoing thromboembolic disease or women with generally recognised risk factors for thromboembolic events, such as personal or family history, thrombophilia or severe obesity (body mass index > 30 kg/m2), treatment with gonadotropins may further increase the risk for aggravation or occurrence of such events. In these women, the benefits of gonadotropin administration need to be weighed against the risks. It should be noted however, that pregnancy itself, as well as OHSS, also carries an increased risk of thromboembolic events.
Reproductive system neoplasms: There have been reports of ovarian and other reproductive system neoplasms, both benign and malignant, in women who have undergone multiple treatment regimens for infertility. It is not yet established whether or not treatment with gonadotropins increases the risk of these tumours in infertile women.
Sodium content: This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. it is essentially “sodium-free”.
See prescribing information for full details.

Common: Headache, abdominal pain, abdominal discomfort, nausea, vomiting, diarrhea, mild or moderate OHSS (including associated symptomatology), ovarian cyst, breast pain, pelvic pain, injection site reaction (e.g. pain, erythema, haematoma, swelling and/or irritation at the site of injection).
See prescribing information for full details.

Should not be administered as a mixture with other medicinal products in the same injection, except follitropin alfa.

Pregnancy:
There is no indication for the use during pregnancy.
Data on a limited number of exposed pregnancies indicate no adverse reactions of gonadotropins on pregnancy, embryonal or foetal development, parturition or postnatal development following controlled ovarian stimulation. No teratogenic effect has been observed in animal studies. In case of exposure during pregnancy, clinical data are not sufficient to exclude a teratogenic effect.
Breast-feeding:
This medicinal product is not indicated during breast-feeding.
Fertility:
This medicinal product is indicated for the stimulation of follicular development, in association with FSH.

The effects of an overdose of this medicinal product are unknown. Nevertheless, there is a possibility that OHSS may occur.
Single doses of up to 40,000 IU of lutropin alfa have been administered to healthy female volunteers without serious adverse reactions and were well tolerated.
Management:
Treatment is directed to symptoms.

Do not store above 25°C.
Store in the original package in order to protect from light.