Patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container. For a complete listing, see the Dosage Forms, Composition and Packaging section of the product monograph; Patients with uncontrolled thyroid or adrenal failure; Patients with active, untreated tumours of the hypothalamus and pituitary gland; Patients who are pregnant or lactating; Ovarian, uterine, or mammary carcinoma; Ovarian enlargement or ovarian cyst unrelated to polycystic ovarian disease and of unknown origin; Abnormal uterine bleeding of unknown origin 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 WARNINGS AND PRECAUTIONS General LUVERIS should only be used by physicians who are thoroughly familiar with the treatment of hypogonadotropic hypogonadism (HH) and its management.
Possible contraindications for pregnancy should be evaluated. In particular, patients should be evaluated for hypothyroidism, adrenocortical insufficiency, hyperprolactinemia and pituitary or hypothalamic tumours, and appropriate specific treatment instituted.
Patients undergoing stimulation of follicular growth are at an increased risk of developing hyperstimulation in view of possible excessive estrogen response and multiple follicular development. In patients with porphyria or a family history of porphyria, Gonadotropins may increase the risk of an acute attack.
Deterioration or a first appearance of this condition may require cessation of treatment. The porphyrias are a group of inherited or acquired disorders of certain enzymes in the heme bio- synthetic pathway. They manifest either by neurological complications or cutaneous disorders or occasionally both.
Symptoms of porphyria attacks may include abdominal pain, nausea/vomiting, personality changes or mental disorders. Acute attacks of porphyria are usually ascribed to environmental factors, certain drugs, infections, alcohol, fasting and stress.
Sex hormones have also been described as playing a key role in the onset of porphyria attacks. Women are at least three times more likely than men to LUVERIS® Product Monograph Page 5 of 30 experience an acute attack and in some women (10-30%), attacks are clearly related to the pre- menstrual phase of the menstrual cycle.
As LUVERIS and GONAL-F are both associated with supra-physiological levels of estrogens, there is a theoretical risk that both gonadotropins would precipitate attack of porphyria. Only isolated cases have been reported after ovarian stimulation by gonadotropins.
The patient should be informed: Of the duration of treatment and monitoring of their condition that will be required Of her personal risk of ovarian hyperstimulation syndrome That there is a potential risk of multiple births Carcinogenesis and Mutagenesis Long-term studies to evaluate the carcinogenic potential of LUVERIS in animals have not been performed.
In vitro mutagenicity testing of LUVERIS in bacteria and mammalian cell lines, chromosome aberration assay in human lymphocytes and in vivo mouse micronucleus have shown no indication of genetic defects. Impaired fertility has been reported in animals exposed to high doses of lutropin alfa; increased pre- and post-implantation losses were observed in female rats and rabbits given lutropin alfa at doses of 10 IU/kg/day and higher.
Cardiovascular As with other gonadotropin products, a potential for arterial thromboembolism exists.
Thromboembolic Events:
In women with recent or ongoing thromboembolic disease or with generally recognised risk factors for thrombo-embolic events, such as personal or family history, 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 ovarian hyperstimulation syndrome (OHSS), also carries an increased risk of thrombo-embolic events.
Sexual Function/Reproduction Ovarian Enlargement:
Mild to moderate uncomplicated ovarian enlargement, which may be accompanied by abdominal distension and/or abdominal pain, may occur in patients treated with gonadotropins such as LUVERIS. These conditions generally regress without treatment within two or three weeks.
Careful monitoring of ovarian response can further minimize the risk of overstimulation. If the ovaries are abnormally enlarged on the last day of therapy with LUVERIS and GONAL-F, human chorionic gonadotropin (hCG) should not be administered in this course of therapy.
This will reduce the risk of development of OHSS.
LUVERIS® Product Monograph Page 6 of 30 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. OHSS is a medical event distinct from uncomplicated ovarian enlargement.
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. Severe OHSS may progress rapidly (within 24 hours to several days) to become a serious medical event. It is characterized by an increase in vascular permeability, which can result in a rapid accumulation of fluid in the peritoneal cavity, thorax, and potentially, the pericardium.
Clinical evaluation may reveal hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress. Very rarely, […]