Pasireotide: Somatostatin analog for Cushing disease

Abstract

Anew somatostatin analog, pasireotide (Signifor—Novartis), has been approved for the treatment of adult patients with Cushing disease for whom pituitary surgery is not an option or has not been curative. The drug works by binding and activating somatostatin receptors, which are generally overexpressed in patients with Cushing disease, resulting in inhibition of adrenocorticotropic hormone secretion and decreased cortisol secretion.■Educate patients on the proper administration of pasireotide.■Hypocortisolism and hyperglycemia can occur with pasireotide.Patients self-administer pasireotide as a subcutaneous injection twice daily. According to the manufacturer, the product is expected to be available in March in 0.3 mg/mL, 0.6 mg/mL, and 0.9 mg/mL strengths.Managing Cushing diseaseCushing disease is a rare disorder that occurs as a result of a corticotropinsecreting pituitary adenoma. If left untreated, the disease can cause substantial morbidities, such as cardiovascular, metabolic, respiratory, and psychiatric complications; bone de-mineralization; and increased susceptibility to infections.Pituitary surgery is the primary treatment modality, with remission rates ranging between 65% and 90%. Second-line treatment options are limited for patients who experience a recurrence, however. These options include repeat surgery, radiation, bilateral adrenalectomy, and medical therapies. Pasireotide offers clinicians a pharmacological therapy that can be used in patients with recurrence or who are not candidates for surgery.Patient counselingGive patients the drug’s Medication Guide and review it with them. Educate patients on the proper administration of pasireotide, which includes gently pinching the skin at the injection site, holding the syringe at a 45° angle, and then injecting the medication into the top of the thigh or abdomen. Inform patients to avoid multiple injections at the same site and not to use the same injection site for two consecutive injections. Discuss signs and symptoms of potential adverse events with patients; these include weakness and fatigue associated with low cortisol levels and excessive thirst, high urine output, and increased weight loss associated with high blood sugar.Clinical dataApproval was based on data from a multicenter Phase III study conducted in 162 patients with persistent or recurrent Cushing disease despite pituitary surgery or de novo patients who were not candidates for surgery; trial results were published last year in the March 8 issue of the New England Journal of Medicine. Patients were given either pasireotide 0.6 mg twice daily (n=82) or 0.9 mg twice daily (n=80), with doses increased after 3 months if indicated.After 6 months of therapy, 15% and 26% of patients in the 0.6 mg and 0.9 mg groups, respectively, reached the primary endpoint of normalization of mean 24-hour urinary free cortisol (UFC) levels. In addition, the percentages of patients with mean UFC no greater than the upper limit of normal or at least a 50% reduction from baseline—a less stringent requirement than the primary endpoint—were 34% in the 0.6 mg and 41% in the 0.9 mg groups, respectively. The most common adverse reactions occurring in at least 20% of patients were diarrhea, nausea, hyperglycemia, cholelithiasis, headache, abdominal pain, fatigue, and diabetes.Pasireotide (Signifor)Manufacturer: NovartisDrug class: Somatostatin analogIndication: Treatment of Cushing diseaseDosage: Initial dose of 0.6 mg or 0.9 mg given by subcutaneous injection twice daily. The dosing range is 0.3 mg to 0.9 mg twice daily based on response and tolerability■An initial dose of 0.3 mg twice daily is recommended for patients with moderate hepatic impairment, up to a maximum dose of 0.6 mg twice daily; pasireotide should not be used in those with severe hepatic impairment.Of note: Warning and precautions associated with use of pasireotide include hypocortisolism, hyperglycemia, bradycardia and QT prolongation, liver function elevations, and cholelithiasis.■Assess baseline levels of fasting plasma glucose, glycosylated hemoglobin, and liver function and conduct baseline electrocardiogram and gallbladder ultrasound tests before starting pasireotide. Optimize the antidiabetes regimen for patients with poorly controlled diabetes before initiating treatment with pasireotide. Monitoring these parameters during treatment is also recommended.In a letter to the editor published in the May 31, 2012, issue of the New England Journal of Medicine, Giovanni Targher, MD, commented on pasireotide’s role in therapy, writing, “Since alternative therapies (including bilateral adrenalectomy) are available for patients with persistent or recurrent Cushing’s disease, it would be important to consider all options before embarking on what might turn out to be many years of medication.” Anew somatostatin analog, pasireotide (Signifor—Novartis), has been approved for the treatment of adult patients with Cushing disease for whom pituitary surgery is not an option or has not been curative. The drug works by binding and activating somatostatin receptors, which are generally overexpressed in patients with Cushing disease, resulting in inhibition of adrenocorticotropic hormone secretion and decreased cortisol secretion.■Educate patients on the proper administration of pasireotide.■Hypocortisolism and hyperglycemia can occur with pasireotide. ■Educate patients on the proper administration of pasireotide.■Hypocortisolism and hyperglycemia can occur with pasireotide. ■Educate patients on the proper administration of pasireotide.■Hypocortisolism and hyperglycemia can occur with pasireotide. Patients self-administer pasireotide as a subcutaneous injection twice daily. According to the manufacturer, the product is expected to be available in March in 0.3 mg/mL, 0.6 mg/mL, and 0.9 mg/mL strengths. Managing Cushing diseaseCushing disease is a rare disorder that occurs as a result of a corticotropinsecreting pituitary adenoma. If left untreated, the disease can cause substantial morbidities, such as cardiovascular, metabolic, respiratory, and psychiatric complications; bone de-mineralization; and increased susceptibility to infections.Pituitary surgery is the primary treatment modality, with remission rates ranging between 65% and 90%. Second-line treatment options are limited for patients who experience a recurrence, however. These options include repeat surgery, radiation, bilateral adrenalectomy, and medical therapies. Pasireotide offers clinicians a pharmacological therapy that can be used in patients with recurrence or who are not candidates for surgery.Patient counselingGive patients the drug’s Medication Guide and review it with them. Educate patients on the proper administration of pasireotide, which includes gently pinching the skin at the injection site, holding the syringe at a 45° angle, and then injecting the medication into the top of the thigh or abdomen. Inform patients to avoid multiple injections at the same site and not to use the same injection site for two consecutive injections. Discuss signs and symptoms of potential adverse events with patients; these include weakness and fatigue associated with low cortisol levels and excessive thirst, high urine output, and increased weight loss associated with high blood sugar. Cushing disease is a rare disorder that occurs as a result of a corticotropinsecreting pituitary adenoma. If left untreated, the disease can cause substantial morbidities, such as cardiovascular, metabolic, respiratory, and psychiatric complications; bone de-mineralization; and increased susceptibility to infections. Pituitary surgery is the primary treatment modality, with remission rates ranging between 65% and 90%. Second-line treatment options are limited for patients who experience a recurrence, however. These options include repeat surgery, radiation, bilateral adrenalectomy, and medical therapies. Pasireotide offers clinicians a pharmacological therapy that can be used in patients with recurrence or who are not candidates for surgery.Patient counselingGive patients the drug’s Medication Guide and review it with them. Educate patients on the proper administration of pasireotide, which includes gently pinching the skin at the injection site, holding the syringe at a 45° angle, and then injecting the medication into the top of the thigh or abdomen. Inform patients to avoid multiple injections at the same site and not to use the same injection site for two consecutive injections. Discuss signs and symptoms of potential adverse events with patients; these include weakness and fatigue associated with low cortisol levels and excessive thirst, high urine output, and increased weight loss associated with high blood sugar. Give patients the drug’s Medication Guide and review it with them. Educate patients on the proper administration of pasireotide, which includes gently pinching the skin at the injection site, holding the syringe at a 45° angle, and then injecting the medication into the top of the thigh or abdomen. Inform patients to avoid multiple injections at the same site and not to use the same injection site for two consecutive injections. Discuss signs and symptoms of potential adverse events with patients; these include weakness and fatigue associated with low cortisol levels and excessive thirst, high urine output, and increased weight loss associated with high blood sugar. Give patients the drug’s Medication Guide and review it with them. Educate patients on the proper administration of pasireotide, which includes gently pinching the skin at the injection site, holding the syringe at a 45° angle, and then injecting the medication into the top of the thigh or abdomen. Inform patients to avoid multiple injections at the same site and not to use the same injection site for two consecutive injections. Discuss signs and symptoms of potential adverse events with patients; these include weakness and fatigue associated with low cortisol levels and excessive thirst, high urine output, and increased weight loss associated with high blood sugar. Clinical dataApproval was based on data from a multicenter Phase III study conducted in 162 patients with persistent or recurrent Cushing disease despite pituitary surgery or de novo patients who were not candidates for surgery; trial results were published last year in the March 8 issue of the New England Journal of Medicine. Patients were given either pasireotide 0.6 mg twice daily (n=82) or 0.9 mg twice daily (n=80), with doses increased after 3 months if indicated.After 6 months of therapy, 15% and 26% of patients in the 0.6 mg and 0.9 mg groups, respectively, reached the primary endpoint of normalization of mean 24-hour urinary free cortisol (UFC) levels. In addition, the percentages of patients with mean UFC no greater than the upper limit of normal or at least a 50% reduction from baseline—a less stringent requirement than the primary endpoint—were 34% in the 0.6 mg and 41% in the 0.9 mg groups, respectively. The most common adverse reactions occurring in at least 20% of patients were diarrhea, nausea, hyperglycemia, cholelithiasis, headache, abdominal pain, fatigue, and diabetes.Pasireotide (Signifor)Manufacturer: NovartisDrug class: Somatostatin analogIndication: Treatment of Cushing diseaseDosage: Initial dose of 0.6 mg or 0.9 mg given by subcutaneous injection twice daily. The dosing range is 0.3 mg to 0.9 mg twice daily based on response and tolerability■An initial dose of 0.3 mg twice daily is recommended for patients with moderate hepatic impairment, up to a maximum dose of 0.6 mg twice daily; pasireotide should not be used in those with severe hepatic impairment.Of note: Warning and precautions associated with use of pasireotide include hypocortisolism, hyperglycemia, bradycardia and QT prolongation, liver function elevations, and cholelithiasis.■Assess baseline levels of fasting plasma glucose, glycosylated hemoglobin, and liver function and conduct baseline electrocardiogram and gallbladder ultrasound tests before starting pasireotide. Optimize the antidiabetes regimen for patients with poorly controlled diabetes before initiating treatment with pasireotide. Monitoring these parameters during treatment is also recommended.In a letter to the editor published in the May 31, 2012, issue of the New England Journal of Medicine, Giovanni Targher, MD, commented on pasireotide’s role in therapy, writing, “Since alternative therapies (including bilateral adrenalectomy) are available for patients with persistent or recurrent Cushing’s disease, it would be important to consider all options before embarking on what might turn out to be many years of medication.” Approval was based on data from a multicenter Phase III study conducted in 162 patients with persistent or recurrent Cushing disease despite pituitary surgery or de novo patients who were not candidates for surgery; trial results were published last year in the March 8 issue of the New England Journal of Medicine. Patients were given either pasireotide 0.6 mg twice daily (n=82) or 0.9 mg twice daily (n=80), with doses increased after 3 months if indicated. After 6 months of therapy, 15% and 26% of patients in the 0.6 mg and 0.9 mg groups, respectively, reached the primary endpoint of normalization of mean 24-hour urinary free cortisol (UFC) levels. In addition, the percentages of patients with mean UFC no greater than the upper limit of normal or at least a 50% reduction from baseline—a less stringent requirement than the primary endpoint—were 34% in the 0.6 mg and 41% in the 0.9 mg groups, respectively. The most common adverse reactions occurring in at least 20% of patients were diarrhea, nausea, hyperglycemia, cholelithiasis, headache, abdominal pain, fatigue, and diabetes.Pasireotide (Signifor)Manufacturer: NovartisDrug class: Somatostatin analogIndication: Treatment of Cushing diseaseDosage: Initial dose of 0.6 mg or 0.9 mg given by subcutaneous injection twice daily. The dosing range is 0.3 mg to 0.9 mg twice daily based on response and tolerability■An initial dose of 0.3 mg twice daily is recommended for patients with moderate hepatic impairment, up to a maximum dose of 0.6 mg twice daily; pasireotide should not be used in those with severe hepatic impairment.Of note: Warning and precautions associated with use of pasireotide include hypocortisolism, hyperglycemia, bradycardia and QT prolongation, liver function elevations, and cholelithiasis.■Assess baseline levels of fasting plasma glucose, glycosylated hemoglobin, and liver function and conduct baseline electrocardiogram and gallbladder ultrasound tests before starting pasireotide. Optimize the antidiabetes regimen for patients with poorly controlled diabetes before initiating treatment with pasireotide. Monitoring these parameters during treatment is also recommended. Manufacturer: NovartisDrug class: Somatostatin analogIndication: Treatment of Cushing diseaseDosage: Initial dose of 0.6 mg or 0.9 mg given by subcutaneous injection twice daily. The dosing range is 0.3 mg to 0.9 mg twice daily based on response and tolerability■An initial dose of 0.3 mg twice daily is recommended for patients with moderate hepatic impairment, up to a maximum dose of 0.6 mg twice daily; pasireotide should not be used in those with severe hepatic impairment.Of note: Warning and precautions associated with use of pasireotide include hypocortisolism, hyperglycemia, bradycardia and QT prolongation, liver function elevations, and cholelithiasis.■Assess baseline levels of fasting plasma glucose, glycosylated hemoglobin, and liver function and conduct baseline electrocardiogram and gallbladder ultrasound tests before starting pasireotide. Optimize the antidiabetes regimen for patients with poorly controlled diabetes before initiating treatment with pasireotide. Monitoring these parameters during treatment is also recommended. Manufacturer: Novartis Drug class: Somatostatin analog Indication: Treatment of Cushing disease Dosage: Initial dose of 0.6 mg or 0.9 mg given by subcutaneous injection twice daily. The dosing range is 0.3 mg to 0.9 mg twice daily based on response and tolerability■An initial dose of 0.3 mg twice daily is recommended for patients with moderate hepatic impairment, up to a maximum dose of 0.6 mg twice daily; pasireotide should not be used in those with severe hepatic impairment. Of note: Warning and precautions associated with use of pasireotide include hypocortisolism, hyperglycemia, bradycardia and QT prolongation, liver function elevations, and cholelithiasis.■Assess baseline levels of fasting plasma glucose, glycosylated hemoglobin, and liver function and conduct baseline electrocardiogram and gallbladder ultrasound tests before starting pasireotide. Optimize the antidiabetes regimen for patients with poorly controlled diabetes before initiating treatment with pasireotide. Monitoring these parameters during treatment is also recommended. In a letter to the editor published in the May 31, 2012, issue of the New England Journal of Medicine, Giovanni Targher, MD, commented on pasireotide’s role in therapy, writing, “Since alternative therapies (including bilateral adrenalectomy) are available for patients with persistent or recurrent Cushing’s disease, it would be important to consider all options before embarking on what might turn out to be many years of medication.”