AHFS Class:

• Somatostatin Agonists 68:29.04

Brands:

• Palsonify^®

Generic Name(s):

• Paltusotine Hydrochloride

Paltusotine is a somatostatin receptor agonist.1

Paltusotine has the following uses:

Paltusotine 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. 1

General

Paltusotine hydrochloride is available in the following dosage form(s) and strength(s):

Tablets: 20 mg and 30 mg of paltusotine1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

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. 1
• Recommended initial dosage of paltusotine is 40 mg once daily.1 During initiation, paltusotine may be temporarily reduced to 20 mg once daily if needed, based on tolerability.1 Once adverse reactions have resolved, resume paltusotine 40 mg once daily. 1
• After 2 to 4 weeks, based on IGF-1 levels, titrate to 60 mg once daily. 1
• Dosage adjustments may be necessary for drug interactions.1 See Full Prescribing Information for additional information.1

Contraindications

• None1

Warnings/Precautions

Cholelithiasis

Paltusotine may inhibit gallbladder contractility and decrease bile secretion, which may lead to gallbladder stones or sludge.1 Cholelithiasis was reported in participants treated with paltusotine in clinical trials.1 Complications of cholelithiasis, such as acute cholecystitis and pancreatitis, have also been reported with the use of paltusotine.1 Monitor patients periodically.1 If complications of cholelithiasis occur, discontinue paltusotine and treat appropriately. 1

Hyperglycemia and Hypoglycemia

Paltusotine may alter the balance between the counter-regulatory hormones, insulin, glucagon, and growth hormone, which may result in hypoglycemia, hyperglycemia, or diabetes mellitus.1 Hyperglycemia was reported in participants treated with paltusotine in clinical trials.1 Monitor blood glucose levels when paltusotine treatment is initiated or when the dose is altered.1 Adjust antidiabetic treatment accordingly. 1

Cardiovascular Abnormalities

Cardiac conduction abnormalities and other ECG changes such as PR interval prolongation have occurred during treatment with paltusotine.1 Bradycardia, sinus arrest, and atrioventricular block were reported in participants treated with paltusotine in clinical trials.1 These ECG changes may occur in patients with acromegaly.1 Dosage adjustments of concomitantly used drugs that have bradycardia effects (e.g., beta-blockers) may be necessary. 1

Thyroid Function Abnormalities

Somatostatin analogs may suppress the secretion of thyroid-stimulating hormone, which may result in hypothyroidism.1 Periodic assessment of thyroid function (TSH, total, and/or free T₄) is recommended during treatment with paltusotine. 1

Steatorrhea and Malabsorption of Dietary Fats

New onset steatorrhea, stool discoloration, and loose stools have been reported in patients receiving somatostatin analogs.1 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.1 If new occurrence or worsening of these symptoms are reported in patients receiving paltusotine, evaluate patients for potential pancreatic exocrine insufficiency and manage accordingly. 1

Vitamin B12 Deficiency

Decreased vitamin B₁₂ levels have been observed in patients treated with somatostatin analogs, including paltusotine.1 Monitor vitamin B₁₂ levels during treatment with paltusotine if clinically indicated. 1

Specific Populations

Pregnancy

The available data with paltusotine use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.1 In animal reproduction studies, no malformations were observed with oral administration of paltusotine to pregnant rats and rabbits during organogenesis at exposures 11 and 3 times the human exposure at the maximum recommended human dose (MRHD) of 60 mg once daily, respectively. 1

The background risk of major birth defects and miscarriage for the indicated population is unknown.1 All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.1 In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. 1

Lactation

There is no information available on the presence of paltusotine in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production.1 Paltusotine is present in animal milk.1 When a drug is present in animal milk, it is likely to be present in human milk.1 The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for paltusotine and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition. 1

Pediatric Use

The safety and efficacy of paltusotine have not been established in pediatric patients. 1

Geriatric Use

In the Phase 3 studies, 17/84 (20.2%) paltusotine-treated participants were ≥65 years of age.1 No overall differences in safety or effectiveness of paltusotine have been observed between participants 65 years of age and older and younger adult participants.1 No dose adjustments are required based on age. 1

Hepatic Impairment

No dosage adjustment of paltusotine is recommended for patients with hepatic impairment.1 In a clinical pharmacology study in participants with varying degrees of hepatic impairment, exposures of paltusotine were similar across all hepatic impairment groups when compared with participants with normal hepatic function. 1

Common Adverse Effects

Most common adverse reactions (≥5%) are diarrhea, abdominal pain, nausea, decreased appetite, sinus bradycardia, hyperglycemia, palpitations, and gastroenteritis.1

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

• Strong CYP3A4 Inducers: May decrease paltusotine exposure and require paltusotine dosage increase. 1
• Moderate CYP3A4 Inducers: May decrease paltusotine exposure and require paltusotine dosage increase. 1
• Proton Pump Inhibitors: May decrease paltusotine exposure and require paltusotine dosage increase.1
• Cyclosporine: may decrease cyclosporine exposure and require cyclosporine dosage adjustment. 1

Actions

Mechanism of Action

Similar to the natural hormone somatostatin, paltusotine suppresses growth hormone (GH) and insulin-like growth factor-1 (IGF-1) secretion.1 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.1 Paltusotine inhibited cyclic adenosine monophosphate accumulation via human SSTR2 activation with an average drug (agonist) concentration that results in half-maximal response (EC₅₀) of 0.25 nM. 1

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Patient Information). 1
• Advise patients to contact their healthcare provider if they experience signs or symptoms of gallstones (cholelithiasis) or complications of cholelithiasis (e.g., cholecystitis, cholangitis, and pancreatitis).1
• Advise patients to contact their healthcare provider if they have problems with blood sugar levels, either hyperglycemia or hypoglycemia. 1
• Advise patients to contact their healthcare provider if they notice irregular heartbeat.1
• Advise patients that their thyroid function may be assessed periodically.1
• Advise patients to contact their healthcare provider if they experience new or worsening symptoms of steatorrhea, loose stools, abdominal bloating, weight loss.1
• Advise patients that Vitamin B₁₂ levels may be monitored during treatment.1

Additional Information

AHFS first Release^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

1. Crinetics Pharmaceuticals, Inc. PALSONIFY^® (PALTUSOTINE) ORAL prescribing information. 2025 Sep. [Web]