Palsonify (paltusotine HCl)

Paltusotine is commercially available as the hydrochloride salt; dosage is expressed in terms of paltusotine.

Patients taking strong cytochrome P-450 (CYP) 3A4 inducers may need a higher paltusotine dosage; do not exceed a 3-fold increase or 120 mg daily, whichever is lower.

Patients taking moderate CYP3A4 inducers may need a higher paltusotine dosage; do not exceed a 2-fold increase or 120 mg daily, whichever is lower.

Patients taking proton pump inhibitors (PPIs) may require an increased paltusotine dosage; avoid PPIs in patients already receiving paltusotine 60 mg daily.

No dosing information is available for this tab.

No dosing information is available for this tab.

Paltusotine is metabolized in the liver mainly through glucuronidation, primarily via uridine diphosphate glucuronosyltransferase (UGT) 1A1 and UGT1A9, with oxidation as a secondary pathway mediated mainly by cytochrome P450 (CYP) 3A4/5 and to a lesser extent by CYP2D6.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Somatostatin Analogs/Gallium Ga 68 Dotatate; Ga 68 Dotatoc

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Both somatostatin analogs and gallium Ga 68 dotatate/ gallium Ga 68 dotatoc bind to the same somatostatin receptors, resulting in competitive inhibition.(1)

CLINICAL EFFECTS: Concurrent use of gallium Ga 68 dotatate/ gallium Ga 68 dotatoc and somatostatin analogs may affect the results of the scan.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: In patients receiving somatostatin analogs, perform the image just prior to dosing with long-acting somatostatin analogs. Short acting somatostatin analogs can be used up to 24 hours before imaging with gallium Ga 68 dotatate or gallium Ga 68 dotatoc. (1)

DISCUSSION: Both somatostatin analogs and gallium Ga 68 dotatate/ gallium Ga 68 dotatoc bind to the same somatostatin receptors, resulting in competitive inhibition, which can affect the results of the scan.(1)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Paltusotine (< 60 Mg)/Proton Pump Inhibitors

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The aqueous solubility of paltusotine is pH dependent. Higher gastric pH leads to lower solubility which may reduce paltusotine absorption.(1)

CLINICAL EFFECTS: Coadministration of proton pump inhibitors (PPIs) may reduce the bioavailability of paltusotine, leading to decreased systemic levels and effectiveness.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of paltusotine states that concomitant use of paltusotine with PPIs may require an increased dosage of paltusotine. Patients who are already on paltusotine 60 mg daily should avoid concomitant use with PPIs.(1)

DISCUSSION: In an interaction study, paltusotine area-under-the-curve (AUC) was decreased by 21% with 20 mg dose and 42% with 60 mg dose levels.(1)

Paltusotine/Moderate Cyp3a4 Inducers

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Moderate CYP3A4 inducers may induce the metabolism of paltusotine.(1)

CLINICAL EFFECTS: Concurrent or recent use of moderate CYP3A4 inducers may alter the clinical effectiveness of paltusotine.(1)

PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.

PATIENT MANAGEMENT: Patients taking moderate CYP3A4 inducers may require an increased dosage of paltusotine.(1) The manufacturer of paltusotine states do not exceed two-fold the paltusotine dosage prior to concomitant use or 120 mg daily, whichever is less.(1) Monitor patients receiving concurrent therapy for reduced efficacy.

DISCUSSION: Paltusotine is metabolized by CYP3A4.(1) Moderate CYP3A4 inducers such as efavirenz are predicted to decrease concentration maximum (Cmax) and area-under-curve (AUC) of paltusotine approximately 5% and 30%, respectively.(1) In an interaction study, paltusotine concentration maximum (Cmax) and area-under-curve (AUC) decreased by 44% and 70%, respectively, following concomitant administration of carbamazepine (strong CYP3A inducer).(1) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, fexinidazole, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat, thioridazine, and tovorafenib.(2,3)

Paltusotine/Strong Cyp3a4 Inducers

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Strong CYP3A4 inducers may induce the metabolism of paltusotine.(1)

CLINICAL EFFECTS: Concurrent or recent use of strong CYP3A4 inducers may alter the clinical effectiveness of paltusotine.(1)

PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.

PATIENT MANAGEMENT: Patients taking strong CYP3A4 inducers may require an increased dosage of paltusotine.(1) The manufacturer of paltusotine states do not exceed three-fold the paltusotine dosage prior to concomitant use or 120 mg daily, whichever is less.(1) Monitor patients receiving concurrent therapy for reduced efficacy.

DISCUSSION: Paltusotine is metabolized by CYP3A4.(1) In an interaction study, paltusotine concentration maximum (Cmax) and area-under-curve (AUC) decreased by 44% and 70%, respectively, following concomitant administration of carbamazepine (strong CYP3A inducer).(1) Strong CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine and St John's Wort.(2,3)

*None.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

• Bradycardia
• Diabetes mellitus
• Exocrine pancreatic insufficiency
• Hypothyroidism
• Vitamin b12 deficiency

Most common adverse reactions (>=5%) of paltusotine are diarrhea, abdominal pain, nausea, decreased appetite, sinus bradycardia, hyperglycemia, palpitations, and gastroenteritis.

There are no severe adverse reactions for this drug.

More Frequent

• Acute abdominal pain
• Diarrhea

Less Frequent

• Anorexia
• Biliary calculus
• Gastroenteritis
• Hyperglycemia
• Nausea
• Palpitations
• Sinus bradycardia

Rare or Very Rare

• Vitamin b12 deficiency

No enhanced messaging available.

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

Data in pregnant patients are insufficient to determine whether paltusotine poses risks for birth defects or pregnancy loss. Animal studies in rats and rabbits showed no malformations at exposures up to 11- and 3-times the human exposure at the maximum recommended dose.

The presence of paltusotine in human milk and its effects on infants or milk production are unknown. Because paltusotine is found in animal milk at higher levels than in plasma, transfer into human milk is possible. The benefits of breastfeeding should be weighed against the mother's clinical need for paltusotine and any potential risks to the infant.

The manufacturer makes no specific dosage recommendations in geriatric patients.

In phase 3 trials, 20.2% of paltusotine-treated patients were >=65 years of age. No safety or efficacy differences were observed between older and younger adults, and no age-based dose adjustments are needed.