Increlex

HOS-094446 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile Adverse reaction data was taken from a total of 413 clinical trial patients with IGFD, including 92 patients with severe primary IGFD. Data was also collected from post-marketing sources. The most frequently reported adverse reactions from the clinical trials were headache (44%), hypoglycaemia (28%), vomiting (26%), injection site hypertrophy (17%), and otitis media (17%). Intracranial hypertension/increased intracranial pressure occurred in 4 (0.96%) of patients from the clinical trials and occurred in 7 – 9 year old treatment naïve subjects. During clinical trials in other indications totaling approximately 300 patients, reports of local and/or systemic hypersensitivity were received for 8% of patients. There were also reports of systemic hypersensitivity from post-marketing use, of which some cases were indicative of anaphylaxis. Post- marketing reports of local allergic reactions were also received. Some patients may develop antibodies to mecasermin. No attenuation of growth was observed as a consequence of the development of antibodies. Tabulated list of adverse reactions Table 1 contains very common (≥ 1/10), common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1000, < 1/100) adverse reactions which occurred in clinical trials. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Other adverse reactions have been identified during post approval use of INCRELEX. As these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency (not known). Table 1: Adverse reactions Reactions observed in the Reactions observed from the System Organ Class clinical trials post-marketing environment Blood and lymphatic system Common: Thymus hypertrophy disorders 6 Immune system disorders Not known: Systemic hypersensitivity (anaphylaxis, generalized urticaria, angioedema, dyspnoea), local allergic reactions at the

Auszug; vollständigen Abschnitt im Original lesen.

HOS-094442 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 3 INCRELEX is contraindicated in children and adolescents with active or suspected neoplasia, or any condition or medical history which increases the risk of benign or malignant neoplasia. Therapy should be discontinued if evidence of neoplasia develops. As INCRELEX contains benzyl alcohol, it must not be given to premature babies or neonates.

HOS-094441 · has-indication-information · PDF-Seite 2

For the long-term treatment of growth failure in children and adolescents from 2 to 18 years with confirmed severe primary insulin-like growth factor-1 deficiency (Primary IGFD). Severe Primary IGFD is defined by: • height standard deviation score ≤ –3.0 and • basal IGF-1 levels below the 2.5th percentile for age and gender and • GH sufficiency. • Exclusion of secondary forms of IGF-1 deficiency, such as malnutrition, hypopituitarism, hypothyroidism, or chronic treatment with pharmacologic doses of anti-inflammatory steroids. Severe Primary IGFD includes patients with mutations in the GH receptor (GHR), post-GHR signaling pathway, and IGF-1 gene defects; they are not GH deficient, and therefore, they cannot be expected to respond adequately to exogenous GH treatment. In some cases, when deemed necessary, the physician may decide to assist in the diagnosis by performing an IGF-I generation test.

HOS-094444 · has-interaction-information · PDF-Seite 5

No interaction studies have been performed. Doses of insulin and/or other hypoglycaemic medicinal products may need to be reduced (see section 4.4).

HOS-094445 · has-pregnancy-information · PDF-Seite 5

Women of childbearing potential / Contraception in males and females A negative pregnancy test is recommended for all women of child bearing potential prior to treatment with mecasermin. It is also recommended that all women of childbearing potential use adequate contraception during treatment. Pregnancy There are no or limited amount of data for the use of mecasermin in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). The potential risk for humans is unknown. This medicinal product should not be used during pregnancy. 5 Breast-feeding Breast-feeding while taking INCRELEX is not recommended, because there is insufficient information on the excretion of mecasermin in human milk. Fertility Mecasermin has been tested in a rat teratology study with no effects on fœtus up to 16 mg/kg (20 fold the maximum recommended human dose (MRHD) based on body surface area) and in a rabbit teratology with no effects on foetus at dose of 0.5 mg/kg (2 fold the MRHD based on body surface area). Mecasermin has no effects on fertility in rats using intravenous doses 0.25, 1, and 4 mg/day (up to 4 times the clinical exposure with the MRHD based on AUC). The effects of mecasermin on the unborn child have not been studied. Therefore there is insufficient medical information to determine whether there are significant risks to a foetus. Studies have not been conducted with mecasermin in breast-feeding mothers. INCRELEX should not be given to pregnant or nursing women. A negative pregnancy test and adequate contraception is required in all pre- menopausal women receiving INCRELEX.

HOS-094443 · has-warning-information · PDF-Seite 4

Benign and malignant neoplasms There is an increased risk of benign and malignant neoplasia in children and adolescents treated with INCRELEX, since IGF-1 plays a role in the initiation and progression of benign and malignant tumours. There have been post-marketing reports of both benign and malignant neoplasms in children and adolescents who have received treatment with INCRELEX. These cases represented a variety of different malignancies and included rare malignancies usually not seen in children (see section 4.8). The increased risk of neoplasia may be higher in patients who receive INCRELEX for unapproved uses or at higher than recommended doses. Current knowledge of IGF-1 biology suggests that IGF-1 plays a role in malignancies in all organs and tissues. Physicians should therefore be vigilant of any symptoms of potential malignancy. If benign or malignant neoplasia develops, INCRELEX treatment should be discontinued definitely and appropriate expert medical care sought. Mecasermin is not a substitute for GH treatment. Mecasermin should not be used for growth promotion in patients with closed epiphyses. Mecasermin should be administered shortly before or after a meal or snack, because it may have insulin-like hypoglycaemic effects. Special attention should be paid to young children, children with a history of hypoglycaemia and children with inconsistent food intake. Patients should avoid engaging in any high-risk activities within 2-3 hours after dosing, particularly at the initiation of mecasermin treatment, until a well-tolerated dose of INCRELEX has been established. If a person with severe hypoglycemia is unconscious or otherwise unable to ingest food normally, an injection of glucagon may be required. Persons with a history of severe hypoglycemia should have glucagon available. At the time of initial prescription, physicians should educate parents on the signs, symptoms and treatment of hypoglycaemia, including injection of glucagon. Doses of insulin and/or other hypoglycaemic medicinal products may need to be reduced for diabetic subjects using this medicinal product. Echocardiogram is recommended before initiation of mecasermin treatment in all patients. Patients who terminate treatment should also have an echocardiogram. Patients with abnormal echocardiogram findings or cardiovascular symptoms should be followed regularly with echocardiogram procedures. Lymphoid tissue (e.g., tonsillar) hypertrophy associated with complications, such a

Auszug; vollständigen Abschnitt im Original lesen.