Signifor

6 mg pasireotide by subcutaneous injection twice a day. Two months after the start of Signifor therapy, patients should be evaluated for clinical benefit. Patients who experience a significant reduction in urinary free cortisol (UFC) levels should continue to receive Signifor for as long as benefit is derived.

6 mg dose is well tolerated by the patient. Patients who have not responded to Signifor after two months of treatment should be considered for discontinuation. Management of suspected adverse reactions at any time during the treatment may require temporary dose reduction of Signifor.

3 mg twice a day is suggested. If a dose of Signifor is missed, the next injection should be administered at the scheduled time. Doses should not be doubled to make up for a missed dose. Switch from intramuscular to subcutaneous formulation There are no clinical data available on switching from the intramuscular to the subcutaneous 3 pasireotide formulation.

6 mg pasireotide twice a day. The patient should be monitored for response and tolerability and further dose adjustments may be needed. Special populations Paediatric population The safety and efficacy of Signifor in children and adolescents aged 0 to 18 years have not been established.

No data are available. 2). 2). Hepatic impairment Dose adjustment is not required in patients with mildly impaired hepatic function (Child Pugh A). 2). 6 mg twice a day. 4). Method of administration Signifor is to be administered subcutaneously by self injection.

Patients should receive instructions from the physician or a healthcare professional on how to inject Signifor subcutaneously. Use of the same injection site for two consecutive injections is not recommended. Sites showing signs of inflammation or irritation should be avoided.

Preferred injection sites for subcutaneous injections are the top of the thighs and the abdomen (excluding the navel or waistline). 6.

Summary of the safety profile A total of 201 Cushing’s disease patients received Signifor in phase II and III studies. The safety profile of Signifor was consistent with the somatostatin analogue class, except for the occurrence of hypocortisolism and degree of hyperglycaemia.

The data described below reflect exposure of 162 Cushing’s disease patients to Signifor in the phase III study. 9 mg Signifor. 8%) were female. 3%) patients had persistent or recurrent Cushing’s disease and few (≤5%) in either treatment group had received previous pituitary irradiation.

0% of patients having at least six months’ exposure. 4% of patients. 5% of patients. Grade 3 and 4 adverse reactions were mostly related to hyperglycaemia. The most common adverse reactions (incidence ≥10%) were diarrhoea, nausea, abdominal pain, cholelithiasis, injection site reactions, hyperglycaemia, diabetes mellitus, fatigue and glycosylated haemoglobin increased.

Tabulated list of adverse reactions Adverse reactions reported up to the cut-off date of the analysis are presented in Table 1. Adverse reactions are listed according to MedDRA primary system organ class. Within each system organ class, adverse reactions are ranked by frequency.

Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Frequencies were defined as follows:

Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); not known (cannot be estimated from the available data). 2% of patients) in the phase III study in Cushing’s disease patients. e. e. e. 30% at month 6). Mean fasting plasma glucose levels commonly increased within the first month of treatment, with decreases and stabilisation observed in subsequent months.

Fasting plasma glucose and HbA1c values generally decreased over the 28 days following pasireotide discontinuation but remained above baseline values. Long-term follow-up data are not available. Patients with baseline HbA1c ≥7% or who were taking antidiabetic medicinal products prior to randomisation tended to have higher mean changes in fasting plasma glucose and HbA1c relative to other patients.

Glucose metabolism Alterations in blood glucose levels have been frequently reported in healthy volunteers and patients treated with pasireotide. 8). The degree of hyperglycaemia appeared to be higher in patients with pre-diabetic conditions or established diabetes mellitus.

8). 9 mg twice daily. e. glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]). Glycaemic status (fasting plasma glucose/haemoglobin A1c [FPG/HbA1c]) should be assessed prior to starting treatment with pasireotide.

FPG/HbA1c monitoring during treatment should follow established guidelines. Self monitoring of blood glucose and/or FPG assessments should be done weekly for the first two to three months and periodically thereafter, as clinically appropriate, as well as over the first two to four weeks after any dose increase.

In addition, monitoring of FPG 4 weeks and HbA1c 3 months after the end of the treatment should be performed. If hyperglycaemia develops in a patient being treated with Signifor, the initiation or adjustment of antidiabetic treatment is recommended, following the established treatment guidelines for the management of hyperglycaemia.

5). There have been post-marketing cases of ketoacidosis with Signifor in patients with and without a history of diabetes. Patients who present with signs and symptoms consistent with severe metabolic acidosis should be assessed for ketoacidosis regardless of diabetes history.

In patients with poor glycaemic control (as defined by HbA1c values >8% while receiving anti-diabetic therapy), diabetes management and monitoring should be intensified prior to initiation and during pasireotide therapy. Liver tests Mild transient elevations in aminotransferases are commonly observed in patients treated with pasireotide.

8). Monitoring of liver function is recommended prior to treatment with pasireotide and after one, two, four, eight and twelve weeks during treatment. Thereafter liver function should be monitored as clinically indicated. Patients who develop increased transaminase levels should be monitored with a second liver function evaluation to confirm the finding.

1. Severe hepatic impairment (Child Pugh C).