paltusotine 20 MG Oral Tablet

INDICATIONS AND USAGE PALSONIFY is indicated for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. PALSONIFY is a somatostatin receptor agonist indicated for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option ( 1 ).

DOSAGE AND ADMINISTRATION Take orally once daily with water on an empty stomach (at least 6 hours after a meal) and at least 1 hour before the next meal ( 2.1 ). Recommended initial dosage is 40 mg once daily. During initiation, PALSONIFY may be temporarily reduced to 20 mg once daily if needed, based on tolerability. Once adverse reactions have resolved, resume PALSONIFY 40 mg once daily ( 2.2 ). After 2 to 4 weeks, based on IGF-1 levels, titrate to 60 mg once daily ( 2.2 ). 2.1 Important Administration Instructions Take PALSONIFY orally once daily with water on an empty stomach, at least 6 hours after a meal (e.g., after overnight fasting) and at least 1 hour before the next meal [see Clinical Pharmacology ( 12.3 )] . 2.2 Recommended Dosage, Titration, and Monitoring The recommended initial dosage of PALSONIFY is 40 mg once daily. During initiation period, PALSONIFY may be temporarily reduced to 20 mg once daily if needed, based on tolerability [see Adverse Reactions ( 6.1 )] . Once adverse reactions have resolved, resume PALSONIFY 40 mg once daily. After 2 to 4 weeks on PALSONIFY 40 mg once daily, based on IGF-1 levels, titrate to a PALSONIFY dosage of 60 mg once daily. 2.3 Dosage Modifications for Drug Interactions Concomitant Use with Strong CYP3A4 Inducers Patients taking strong CYP3A4 inducers may require an increased dosage of PALSONIFY. Do not exceed three-fold the PALSONIFY dosage prior to concomitant use or 120 mg daily, whichever is less [see Drug Interactions ( 7.1 )] . Concomitant Use with Moderate CYP3A4 Inducers Patients taking moderate CYP3A4 inducers may require an increased dosage of PALSONIFY. Do not exceed two-fold the PALSONIFY dosage prior to concomitant use or 120 mg daily, whichever is less [see Drug Interactions ( 7.1 )] . Concomitant Use with Proton Pump Inhibitors Patients taking proton pump inhibitors may require an increased dosage of PALSONIFY. Avoid concomitant use of proton pump inhibitors in patients who are already on PALSONIFY 60 mg [see Drug Interactions ( 7.1 )] .

WARNINGS AND PRECAUTIONS Cholelithiasis and its Complications: Monitor periodically. If complications of cholelithiasis occur, discontinue PALSONIFY and treat appropriately ( 5.1 ). Hyperglycemia and Hypoglycemia: Monitor glucose and adjust antidiabetic treatment as needed ( 5.2 ). Cardiovascular Abnormalities: Bradycardia or conduction abnormalities may occur. Dosage adjustments of concomitantly used drugs with bradycardia effects may be necessary ( 5.3 ). Thyroid Function Abnormalities: Hypothyroidism may occur. Assess thyroid function periodically ( 5.4 ). Steatorrhea and Malabsorption of Dietary Fats: New onset steatorrhea, stool discoloration, loose stools, abdominal bloating, and weight loss may occur. If new occurrence or worsening of these symptoms are reported, evaluate for potential pancreatic exocrine insufficiency ( 5.5 ). Vitamin B 12 Deficiency: Monitor vitamin B 12 levels during treatment if indicated ( 5.6 ). 5.1 Cholelithiasis and its Complications PALSONIFY may inhibit gallbladder contractility and decrease bile secretion, which may lead to gallbladder stones or sludge. Cholelithiasis was reported in participants treated with PALSONIFY in clinical trials. Complications of cholelithiasis, such as acute cholecystitis and pancreatitis, have also been reported with the use of PALSONIFY [see Adverse Reactions ( 6.1 )] . Monitor patients periodically. If complications of cholelithiasis occur, discontinue PALSONIFY and treat appropriately. 5.2 Hyperglycemia and Hypoglycemia PALSONIFY may alter the balance between the counter-regulatory hormones, insulin, glucagon, and growth hormone, which may result in hypoglycemia, hyperglycemia, or diabetes mellitus. Hyperglycemia was reported in participants treated with PALSONIFY in clinical trials [see Adverse Reactions ( 6.1 )] . Monitor blood glucose levels when PALSONIFY treatment is initiated or when the dose is altered. Adjust antidiabetic treatment accordingly. 5.3 Cardiovascular Abnormalities Cardiac conduction abnormalities and other ECG changes such as PR interval prolongation have occurred during treatment with PALSONIFY. Bradycardia, sinus arrest, and atrioventricular block were reported in participants treated with PALSONIFY in clinical trials [see Adverse Reactions ( 6.1 )] . These ECG changes may occur in patients with acromegaly. Dosage adjustments of concomitantly used drugs that have bradycardia effects (e.g., beta-blockers) may be necessary. 5.4 Thyroid Function Abnormalities Somatostatin analogs may suppress the secretion of thyroid-stimulating hormone, which may result in hypothyroidism. Periodic assessment of thyroid function (TSH, total, and/or free T 4 ) is recommended during treatment with PALSONIFY. 5.5 Steatorrhea and Malabsorption of Dietary Fats New onset steatorrhea, stool discoloration and loose stools have been reported in patients receiving somatostatin analogs. Somatostatin analogs reversibly inhibit secretion of pancreatic enzymes and bile acids, which may result in malabsorption of dietary fats and subsequent symptoms of steatorrhea, loose stools, abdominal bloating, and weight loss. If new occurrence or worsening of these symptoms are reported in patients receiving PALSONIFY, evaluate patients for potential pancreatic exocrine insufficiency and manage accordingly. 5.6 Vitamin B 12 Deficiency Decreased vitamin B 12 levels have been observed in patients treated with somatostatin analogs, including PALSONIFY. Monitor vitamin B 12 levels during treatment with PALSONIFY if clinically indicated.

CONTRAINDICATIONS None. None ( 4 )

Mechanism of Action Similar to the natural hormone somatostatin, paltusotine suppresses growth hormone (GH) and insulin-like growth factor-1 (IGF-1) secretion. Paltusotine exerts its pharmacological activity via selective agonism (>4000-fold) at somatostatin receptor 2 (SSTR2) and exhibits little or no affinity for other SST receptor subtypes. Paltusotine inhibited cyclic adenosine monophosphate accumulation via human SSTR2 activation with an average drug (agonist) concentration that results in half-maximal response (EC 50 ) of 0.25 nM.