- Drugs List
- Precautions and Warnings
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Powder and solvent for solution for injection containing 75 IU lutropin alfa (recombinant human luteinising hormone - rhLH) per vial.
Lutropin alfa is produced from genetically engineered Chinese hamster ovary (CHO) cells.
Treatment with lutropin alfa should be initiated and supervised by a specialist experienced in the treatment of fertility disorders.
Self administration should only be carried out by well motivated patients, who have received adequate training and have access to expert advice.
In LH and FSH deficient women, the objective of lutropin alfa 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 gonadotrophin (hCG). Lutropin alfa 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.
Treatment should be tailored to the individual patient's response as assessed by measuring the follicle size by ultrasound and by oestrogen response. A recommended regimen commences at 75 IU of lutropin alfa daily with 75 - 150 IU FSH.
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 lutropin alfa 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 preformed.
Luteal phase support may be considered since lack of substances with luteotrophic activity 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.
Administer by subcutaneous injection.
Self-administration of lutropin alfa should only be performed by patients who are well-motivated, adequately trained and with access to expert advice.
The powder should be reconstituted with the solvent provided by gently swirling, immediately prior to use. The reconstituted solution should not be administered if it contains particles or is not clear.
Lutropin alfa may be mixed with follitropin alfa and co-administered as a single injection. In this case, lutropin alfa should be reconstituted first and then used to reconstitute the follitropin alfa powder.
IncompatibilitiesThis medicinal product must not be mixed with other medicinal products except those mentioned in 'Reconstitution'.
Ovarian, uterine, or mammary carcinoma
Tumours of the hypothalamus and pituitary gland
Ovarian enlargement or cyst unrelated to polycystic ovarian disease
Undiagnosed vaginal bleeding
Primary ovarian failure
Pregnancy ( see Pregnancy )
Breastfeeding ( see Lactation)
Hereditary fructose intolerance
Precautions and Warnings
Treatment should be initiated under the supervision of a physician experienced in the treatment of fertility problems.
Before starting treatment, the couple's infertility should be assessed as appropriate and putative contraindications for pregnancy excluded, for example, ovarian failure, malformation of the sexual organs incompatible with pregnancy or fibroid tumours of the uterus incompatible with pregnancy.
In addition, patients should be evaluated for hypothyroidism, adrenocortical deficiency, hyperprolactinaemia and pituitary or hypothalamic tumours, and appropriate specific treatment given.
Ovarian hyperstimulation syndrome (OHSS) can occur. 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. Very rarely, severe OHSS may be complicated by ovarian torsion or thromboembolic events, such as pulmonary embolism, ischaemic stroke or myocardial infarction.
Clinical evaluation may reveal signs such as hypovolaemia, haemoconcentration, electrolyte imbalances, ascites, pleural effusions, or acute pulmonary distress. 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 ART cycles.
Adherence to recommended dosages and regimens 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.
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. 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 on-going and that the patient be hospitalised and appropriate therapy be started.
Ovarian torsion has been reported after treatment with other gonadotropins. Damage to the ovary due to reduced blood supply man be limited by early diagnosis and immediate treatment. Other risk factors for ovarian torsion include ovarian hyperstimulation syndrome (OHSS), pregnancy, previous abdominal surgery, previous history of ovarian torsion, ovarian cysts of history of ovarian cysts and polycystic ovaries.
Women with generally recognised risk factors for thrombosis (personal or family history, body mass index >30kg per metre squared, thrombophilia) may have an increased risk of venous or arterial thrombotic events during or following treatment with gonadotrophins. It should be noted however, that pregnancy itself, as well as OHSS, also carries an increased risk of thromboembolic events
Risk of multiple pregnancies. Multiple gestation, especially high order, carries an increased risk of adverse maternal and perinatal outcomes. Patients should be advised of the potential risks of multiple pregnancies before starting treatment.
If pregnancy occurs possibility of ectopic pregnancy should be considered. An early ultrasound is recommended to confirm intrauterine pregnancy.
A higher risk of pregnancy loss is observed with women undergoing assisted reproduction techniques (ART).
Incidences of congenital malformations are slightly more common after ART. This is thought to be due to parental characteristics (maternal age, sperm characteristics) and multiple gestations.
Cases of ovarian and other reproductive neoplasms (benign and malignant) have been reported in women undergoing multiple drug infertility treatment. It is currently unclear as to whether gonadotrophins increase the baseline risk of these tumours in infertile women.
Use with caution in patients with porphyria.
The preparation contains sucrose and is contraindicated in patients with hereditary fructose intolerance. In addition, caution is advised in patients with glucose-galactose malabsorption syndrome.
Use in PorphyriaUse with caution in patients with porphyria or a family history of porphyria. Deterioration or a first appearance of this condition may require cessation of treatment. NAPOS classifies lutropin alfa as probably porphyrogenic.
Pregnancy and Lactation
Contraindicated during pregnancy.
There are no known teratogenic effects of gonadotrophins following controlled ovarian hyperstimulation treatment. However, clinical data is insufficient to exclude any teratogenic effects when exposure occurs during pregnancy. No specific malformative effects have been observed during pregnancy.
No teratogenic effect has been observed in animal studies.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Contraindicated during breastfeeding.
Schaefer suggests that due to the low oral bioavailability of the gonadotropins, there would be no adverse effect on the infant (Schaefer 2007).
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Effects on Ability to Drive and Operate Machinery
Lutropin alfa has no or negligible influence on the ability to drive and use machines.
Injection site reactions
Increased risk of ectopic pregnancy
Increased risk of multiple pregnancy
Increased risk of miscarriage
Ovarian hyperstimulation syndrome (OHSS)
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
British National Formulary, 62nd Edition (2011) Pharmaceutical Press, London.
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.
Summary of Product Characteristics: Luveris 75IU. Serono Pharmaceuticals Ltd. Revised October 2011.
The Drug Database for Acute Porphyria (NAPOS)
Available at: https://www.drugs-porphyria.com/languages/UnitedKingdom/s1.php?l=gbr
Lutropin alfa Last revised: October 1, 2004
Last accessed: March 8, 2012
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