Prescribing guide
Palsonify (paltusotine)Dosing, IGF-1 titration, interactions, specialty dispensing and prior authorization criteria for acromegalyFor prescribers and their offices treating acromegaly: what the pharmacy needs before it ships, what the prior authorization wants documented, the titration and the monitoring the label requires.
Dispensing gate
No REMS; specialty dispensing through Biologics by McKesson, Orsini or select pituitary centers after prior authorization; CrinetiCARE product enrollment form faxed to 844-CRN-FAXX (844-276-3299).
Example PA threshold
Cigna example: age 18 or older, inadequate response to or not a candidate for surgery or radiotherapy, pretreatment IGF-1 above ULN, endocrinologist, prior octreotide LAR or lanreotide.
Monitoring
Glucose at initiation and each dose change; IGF-1 at 2 to 4 weeks for titration; periodic gallbladder and thyroid assessment; B12 if indicated; adjust bradycardic drugs as needed.
Support line
CrinetiCARE, 844-CRN-HELP (844-276-4357), benefits investigation, PA and appeals support, copay as low as $0 for commercial plans with up to $25,000 a year, a quick start supply during coverage delays, and a patient assistance program.
Give your patient their plan
A one-page handout for starting Palsonify, in plain language: what the first fill waits on, the first dates, who will call and the symptoms to report, with blank lines for the start date and your office's number. The link opens the patient's full first 90 days page, where their dates become calendar entries.
trialfriend.com/p/palsonifyBefore the first fill: REMS, labs and enrollment
The steps that the pharmacy, the REMS or the drugmaker's program will wait on, in the order they usually need to happen. A first fill of a specialty drug most often stalls on one of these rather than on the plan.
| Step | What it requires | Source |
|---|---|---|
| Document the baseline | Cigna IP0769 asks for a pretreatment IGF-1 above the laboratory's ULN for age and sex, drawn before any somatostatin analog, dopamine agonist or Somavert, plus surgical and radiotherapy history. | Cigna policy |
| Enroll in CrinetiCARE | Fax the product enrollment form to 844-CRN-FAXX (844-276-3299) with both sides of the insurance card. Select 40mg (20mg tablets x2) or 60mg (30mg tablets x2), 2 tablets once daily, ICD-10 E22.0, and list prior acromegaly drugs and doses. CrinetiCARE will obtain the patient's signature if the patient is not in the office. | Enrollment form |
| Route the prescription | Biologics by McKesson (800-850-4306) or Orsini Specialty Pharmacy (847-239-5680). Health systems order through McKesson Specialty Health (800-482-6700) or McKesson Plasma Biologics (877-625-2566). | Access guide |
| New York and Iowa | Send an electronic prescription per state law, to AllCare Plus Pharmacy (NPI 1902167596). | Enrollment form |
| Bridge a slow approval | Quick Start and Bridge Program: free supply while coverage is pending or under appeal, for uninsured patients or insured patients with a documented delay of at least 48 hours after the insurer has all required information. Product may not be billed to any payer and does not count toward deductibles. | CrinetiCARE terms |
| Medication reconciliation | Flag PPIs, strong or moderate CYP3A4 inducers, bradycardic drugs such as beta-blockers, cyclosporine and antidiabetic therapy. | FDA label |
| Switching from a depot | The label gives no switching guidance. In PATHFNDR-1 the first dose was given when the next octreotide or lanreotide injection would have been due. | PATHFNDR-1 paper |
Prior authorization criteria and what to document
One public policy as the example: Cigna, September 1, 2026. Approval a year at a time. Cigna first made this policy effective on January 15, 2026, and its August 13, 2026 review made no criteria changes. It cites the September 2025 label, which is still the current label. Other plans set their own rules. The Blue Cross Blue Shield Federal Employee Program, for one, has no injection-first step. It asks the prescriber to agree to monitor IGF-1, blood sugar, thyroid function, ECG, vitamin B12 and gallstone signs, and allows up to 120mg a day for 12 months. It is here as an example of what a plan asks for, not as a rule.
| Element | What the policy asks | In the chart | Source |
|---|---|---|---|
| Age and diagnosis | 18 or older, with acromegaly | Diagnosis note and ICD-10-CM code E22.0 | Cigna policy |
| Surgery or radiotherapy | Inadequate response to surgery and/or radiotherapy, not an appropriate candidate for either, or negative effects from tumor size such as optic nerve compression | Operative and radiation notes, or the reason neither is an option | Cigna policy |
| Baseline IGF-1 | Pretreatment IGF-1 above ULN for age and gender for the reporting laboratory, before any somatostatin analog, dopamine agonist or Somavert | Lab report with its reference range | Cigna policy |
| Prescriber | Prescribed by or in consultation with an endocrinologist | Specialty on the request, or the consult note | Cigna policy |
| Preferred product | Employer Plans and Individual and Family Plans: tried one of octreotide ER injectable suspension (Sandostatin LAR Depot, generic), Somatuline Depot or lanreotide subcutaneous injection | Prior injection, dose and dates | Cigna policy |
| Quantity | Plans may set per-day tablet limits; Crinetics' sample limits are 2 x 20mg tablets for 40mg and 2 x 30mg tablets for 60mg | Target dose on the prescription and PA request | Access guide |
Palsonify dosing and titration
| When | Label | Source |
|---|---|---|
| Day 1 | 40mg orally once daily with water on an empty stomach, at least 6 hours after a meal (for example after an overnight fast) and at least 1 hour before the next meal. | FDA label |
| During initiation | May reduce temporarily to 20mg once daily for tolerability; resume 40mg once adverse reactions resolve. | FDA label |
| After 2 to 4 weeks | Based on IGF-1, titrate to 60mg once daily, the maximum recommended dose. | FDA label |
| With CYP3A4 inducers | May require an increase: strong inducers up to 3 times the prior dose, moderate inducers up to 2 times, in either case not above 120mg daily. | FDA label |
| With PPIs | May require an increase; avoid PPIs in patients already on 60mg. | FDA label |
| Supply | 20mg pink tablets (NDC 84015-920-60) and 30mg yellow tablets (NDC 84015-930-60), each in a bottle of 60: a 30-day supply at 2 tablets daily. Store at 20 to 25°C, excursions 15 to 30°C, in the original container. | FDA label |
| Missed dose | The label gives no missed-dose instruction. | FDA label |
| Special populations | No adjustment for hepatic impairment or age; no clinically significant PK effect of eGFR 52 to 148 mL/min/1.73m2, body weight or UGT1A1 polymorphism. | FDA label |
Monitoring the Palsonify label requires
| When | What | What the label says to do with it | Source |
|---|---|---|---|
| Initiation and each dose change | Blood glucose | Hyperglycemia, diabetes or hypoglycemia may occur; adjust antidiabetic treatment. Study 1 week 24: FPG +6.9 against +1.5mg/dL, HbA1c +0.26% against +0.04% | FDA label |
| Weeks 2 to 4 | IGF-1 | Titrate to 60mg based on IGF-1; most Study 1 responders normalized within 2 to 4 weeks | FDA label |
| Periodically | Gallbladder | Cholelithiasis or complications in 10 of 173 (6%), mostly within 9 months; one obstructive pancreatitis needed cholecystectomy; discontinue if complications occur | FDA label |
| Periodically | TSH, total and/or free T4 | Somatostatin analogs may suppress TSH and cause hypothyroidism | FDA label |
| First 3 months, and with bradycardic drugs | Heart rate and conduction | Sinus bradycardia 7% against 0 in Study 1, asymptomatic; sinus arrest (2) and complete AV block (1) in open-label extensions in patients with cardiovascular comorbidities; adjust beta-blockers or other bradycardic drugs as needed | FDA label |
| If clinically indicated | Vitamin B12 | Decreased levels seen with somatostatin analogs, including Palsonify | FDA label |
| New or worse steatorrhea | Pancreatic exocrine function | Evaluate for exocrine insufficiency with steatorrhea, stool discoloration, loose stools, bloating or weight loss | FDA label |
| Eyes | Retinal findings | The label requires no eye exam; it reports ocular phototoxicity in rats, and retinal findings without baselines during open-label periods | FDA label |
| Post-approval | Enhanced pharmacovigilance | The FDA asked Crinetics to submit retinal and related eye events as 15-day alert reports through the 5th year after approval | FDA letter |
| Renewal | Clinical status | Cigna approves 1 year at a time and lists no separate renewal criteria | Cigna policy |
Palsonify drug interactions and contraindications
| Label category | Agents and what the label says | Source |
|---|---|---|
| Strong CYP3A4 inducers | Carbamazepine cut paltusotine Cmax about 44% and AUC about 70%; dose may rise to 3 times the prior dose, maximum 120mg daily | FDA label |
| Moderate CYP3A4 inducers | Efavirenz predicted to cut AUC about 30%; dose may rise to 2 times the prior dose, maximum 120mg daily | FDA label |
| Proton pump inhibitors | pH-dependent solubility; AUC down 21% at 20mg and 42% at 60mg; avoid in patients already on 60mg | FDA label |
| Cyclosporine | Cyclosporine Cmax down 53% and AUC down 35%; follow cyclosporine therapeutic drug monitoring | FDA label |
| Bradycardic drugs | Beta-blockers and other drugs that slow heart rate may need dose adjustment | FDA label |
| Food | High-fat meal cut AUC 85% and Cmax 81%; low-fat meal cut AUC 72% and Cmax 68% | FDA label |
| No meaningful effect | Weak CYP3A4 inducers and CYP3A4/5, P-gp or UGT1A1 inhibitors predicted not to matter; no clinically significant effect on CYP3A4/5 or MATE substrates | FDA label |
| Pharmacokinetics | Half-life about 28 hours; steady state within 1 week; no clinically significant QTc prolongation at 4.6 times the maximum dose | FDA label |
Why a first fill stalls, and the fix
- The plan wants an injection tried firstCigna covers Palsonify only after one of octreotide LAR (Sandostatin LAR Depot or its generic), Somatuline Depot or lanreotide injection has been tried. The office lists which injection you used on the request.
- Missing IGF-1 or surgery historyCigna wants an IGF-1 above the normal range from before any acromegaly medicine, plus a note on surgery or radiation. The prescriber must be an endocrinologist or work with one.
- Prior authorization deniedCrinetiCARE helps offices with benefits checks, prior authorization and appeals. Its site gives the office a letter of medical necessity template and an appeal letter template.
- More tablets than the plan allowsCrinetics warns that plans may cap the tablets allowed per day. It tells offices to state the target dose, since both 40mg and 60mg are 2 tablets a day.
- Coverage is taking a whileThe Quick Start and Bridge Program may supply Palsonify free while coverage is pending or under appeal. Insured patients qualify after a documented delay of at least 48 hours once the insurer has all it needs.
- A copay you cannot payCrinetics' guide for offices says commercially insured patients may pay as little as $0, with up to $25,000 in support a year. People covered by federal or government-funded programs are excluded from the copay program.
- Your plan uses a copay maximizer or accumulatorThe copay card terms say patients whose plan runs either program are not eligible to use the card. Call CrinetiCARE to ask what other help may apply.
CrinetiCARE
- One-on-one nurse educators for ongoing support and education during treatment
- Help navigating insurance coverage and finding a specialist near you
- A copay program for commercial insurance, as little as $0, with 12 months of enrollment and no income requirement, not for people covered by state or federal healthcare programs
- A quick start supply so you can begin therapy while insurance coverage is being decided
- A patient assistance program giving Palsonify at no cost to eligible people who are uninsured or whose insurance excludes it, including people on Medicare or Medicaid
- Links to independent foundations, including The Assistance Fund, PAN Foundation, HealthWell Foundation and Patient Advocate Foundation
Questions prescribers' offices ask about Palsonify
What is the Palsonify dose?
The September 2025 label starts at 40mg orally once daily and titrates to 60mg after 2 to 4 weeks based on IGF-1. It is taken with water on an empty stomach at least 6 hours after a meal and at least 1 hour before the next; 20mg is allowed temporarily during initiation for tolerability.
What monitoring does the Palsonify label require?
The September 2025 label asks for blood glucose at initiation and at each dose change, with antidiabetic therapy adjusted as needed. It also calls for periodic gallbladder monitoring, periodic TSH and total or free T4, vitamin B12 if clinically indicated, and evaluation for pancreatic exocrine insufficiency if steatorrhea appears; it sets no ECG schedule.
How do PPIs and CYP3A4 inducers change the Palsonify dose?
PPIs reduced paltusotine AUC by 21% at 20mg and 42% at 60mg in the September 2025 label, which says to avoid PPIs in patients already on 60mg. With strong CYP3A4 inducers the dose may go up to 3 times the prior dose, and with moderate inducers up to 2 times, never above 120mg daily.
How do patients switch from injected octreotide or lanreotide?
The September 2025 label gives no switching instructions. In PATHFNDR-1 the first dose was given when the next octreotide or lanreotide injection would have been due, and 83% against 4% on placebo kept IGF-1 at or below 1.0 times ULN at week 36.
What do insurers ask for to approve Palsonify?
The Cigna policy on this page, effective September 1, 2026, approves 1 year at a time for adults with an inadequate response to surgery or radiotherapy, or who are not candidates. It asks for a pretreatment IGF-1 above ULN, an endocrinologist, and a prior trial of octreotide LAR, Somatuline Depot or lanreotide.
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Sources
- DailyMed - PALSONIFY- paltusotine tablet, film coated (prescribing information and Patient Information, revised September 2025), Crinetics Pharmaceuticals, via DailyMed, 2025-09-16.
- PALSONIFY prescribing information, September 2025 (Drugs@FDA file 219070s000lbl.pdf), FDA, Drugs@FDA, 2025-09-25.
- NDA 219070 approval letter, Palsonify (paltusotine) tablets, September 25, 2025, FDA, 2025-09-25.
- Approved Risk Evaluation and Mitigation Strategies (REMS), FDA, 2026-11-07.
- CrinetiCARE: PALSONIFY™ Patient Assistance Program, Crinetics Pharmaceuticals, 2026-11-07.
- CrinetiCARE for Healthcare Professionals: PALSONIFY™ - Crineticare, Crinetics Pharmaceuticals, 2026-11-07.
- Terms and Conditions - Crineticare, Crinetics Pharmaceuticals, 2026-11-07.
- PALSONIFY Product Enrollment Form (US-PAL-26-0144-2), Crinetics Pharmaceuticals, 2026-11-07.
- Access and reimbursement guide for healthcare providers (HCPs) (US-PAL-2500084-1), Crinetics Pharmaceuticals, 2026-11-07.
- Medicare coverage: A simple guide to understanding Medicare plans and Medicare Part D prescription coverage (US-PAL-2500086-1), Crinetics Pharmaceuticals, 2026-11-07.
- How To Take PALSONIFY™ (paltusotine) for Acromegaly Treatment, Crinetics Pharmaceuticals, 2026-11-07.
- MOA and Dosing for PALSONIFY™ (paltusotine) | HCP, Crinetics Pharmaceuticals, 2026-11-07.
- Acromegaly Disease Control Maintained After Switching From Injected Somatostatin Receptor Ligands to Oral Paltusotine, The Journal of Clinical Endocrinology & Metabolism, 2025-01-01.
- Somatostatin Receptor Agonist – Palsonify, Drug Coverage Policy IP0769, Cigna, 2026-09-01.
- Pharmacy Policy 5.30.099, Palsonify, Blue Cross Blue Shield Federal Employee Program, 2026-04-01.
- Vertex Completes Acquisition of Crinetics Pharmaceuticals and Announces Expansion of Executive Leadership Team, Vertex Pharmaceuticals, 2026-09-01.
A reference drawn from the September 16, 2025 label, the drugmaker's published program and one public insurer policy shown as an example, checked on November 7, 2026. Labels and policies change; the label on DailyMed and the plan's current policy govern. Trial Friend is not a medical provider. It reports what these documents say and does not judge whether a drug is safe or right for any patient; that is the prescriber's decision. Not a substitute for the prescribing information.