Prescribing guide
Signifor (pasireotide)And Signifor LAR baseline testing, glucose and liver monitoring, dosing by formulation and prior authorization criteria for Cushing diseaseFor prescribers and their offices treating Cushing disease: what the pharmacy needs before it ships, what the prior authorization wants documented, the titration and the monitoring the label requires.
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Dispensing gate
No REMS; baseline FPG, HbA1c, liver tests, ECG, potassium and magnesium (plus gallbladder ultrasound per the Signifor label), correction of hypokalemia and hypomagnesemia, prior authorization, and a Patient Prescription Form faxed to Anovo.
Example PA threshold
Cigna example: age 18 or older (Signifor policy), not a surgical candidate or surgery not curative per the prescriber, endocrinologist or Cushing syndrome specialist; 4 months initial, then 1 year with response.
Monitoring
Glucose weekly for the first 2 to 3 months (Signifor) or 3 months (Signifor LAR) and after dose increases; liver tests at 1 to 2 weeks (Signifor) or 2 to 3 weeks (LAR), then monthly for 3 months; ECG, potassium, magnesium, gallbladder and pituitary function periodically.
Support line
Recordati Rare Diseases R.A.R.E. Patient Support 1-888-855-7273 (1-888-855-RARE), fax 1-855-813-2039, $20 co-pay for qualified commercially insured patients, home injection program for Signifor LAR.
Give your patient their plan
A one-page handout for starting Signifor, 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/signifor1
Before 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 |
|---|---|---|
| No REMS, Signifor | The Signifor label has no REMS, no boxed warning and no contraindications. The 2012 approval letter set postmarketing requirements, not a REMS. | Signifor label |
| No REMS, Signifor LAR | The Signifor LAR label has no REMS, no boxed warning and no contraindications. | Signifor LAR label |
| Baseline tests, Signifor | FPG, HbA1c, liver tests, serum potassium and magnesium, a baseline ECG and a gallbladder ultrasound (section 2.2). Pituitary function, such as TSH and free T4 and GH and IGF-1, before initiation (section 5.6). | Signifor label |
| Baseline tests, Signifor LAR | FPG and HbA1c, liver tests, ECG, serum potassium and serum magnesium (section 2.1). Pituitary function, such as thyroid, adrenal and gonadal, before initiation (section 5.5). The Patient Information says an ultrasound of the gallbladder is done before and during treatment. | Signifor LAR label |
| Correct and optimize first | Hypokalemia and hypomagnesemia must be corrected before administration. Poorly controlled diabetes should be intensively optimized with anti-diabetic therapy before starting (Signifor sections 2.2, 5.2 and 5.3; Signifor LAR sections 2.1, 5.1 and 5.2). | Signifor label |
| Medication reconciliation | Review QT-prolonging drugs, anti-arrhythmics, drugs associated with bradycardia, beta-blockers, calcium channel blockers, cyclosporine and bromocriptine (sections 5.3 and 7). | Signifor label |
| Prescription form | One Patient Prescription Form covers both products. Fax to 855-813-2039; the form states it is valid only if faxed directly from the prescriber to Anovo, and stamped signatures are not valid. Refax or call 888-855-7273 if no confirmation fax arrives within 24 hours. | Prescription form |
| Form details | Select newly prescribed or current patient, the ICD-10 code (E24.0 or E24.9 for Cushing disease), and the strength. Signifor is listed as 0.3mg, 0.6mg or 0.9mg ampules, 60 per box, as a 1-month or 3-month supply; Signifor LAR as 10mg, 20mg, 30mg, 40mg or 60mg kits, 1-month supply. The form asks for baseline or most recent laboratory and biomarker values, prior surgery dates and past medication therapies. | Prescription form |
| Supplies and nursing | Signifor supplies (1mL syringe, 27G 1/2 inch needle, 18G 1/2 inch filter needle, alcohol prep pads, bandages, sharps container) ship unless No Supplies is checked. For Signifor LAR, the form asks whether the patient requires or prefers home administration by a skilled nursing visit, or will receive the injection at the prescriber's office, a designated clinic or an infusion provider. | Prescription form |
| Pharmacy routing and office support | All prescriptions are filled through Recordati's specialty pharmacy network. R.A.R.E. lists benefits verification, prior authorization and appeals support, a Copay Assistance Program, financial assistance during insurance gaps and a Patient Assistance Program for indigent patients. Its Mobile Injection Program sends a registered nurse to the home for Signifor LAR at no cost to the patient, insurer or provider. | Signifor LAR HCP support |
| Injection teaching, Signifor | Patients self-inject subcutaneously into the top of the thigh or the abdomen, following the Instructions for Use (section 2.4). The Medication Guide says the patient should not inject until shown how. | Signifor label |
| Administration, Signifor LAR | Reconstituted and given only by a trained healthcare professional, intramuscularly in the right or left gluteus, immediately after reconstitution, never intravenously. The kit must stand at room temperature for at least 30 minutes, not more than 24 hours, and the vial is shaken for a minimum of 30 seconds (sections 2.2 and 2.6). | Signifor LAR label |
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Prior authorization criteria and what to document
One public policy as the example: Cigna, May 1, 2026. Approval approved for 4 months at first for Cushing disease, then for 1 year at a time for people who have responded. This is Cigna policy IP0482 for Signifor, the twice-a-day form, effective May 1, 2026, after an April 9, 2026 review with no criteria changes. It cites the July 2024 Signifor prescribing information, which matches the current label text. Cigna reviews Signifor LAR under a separate policy, IP0165, with the same Cushing disease criteria except that it sets no minimum age. Other plans set their own criteria and their own approval lengths. 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, Signifor | 18 or older | Date of birth on the request | Cigna Signifor policy |
| Surgical status | According to the prescriber, the patient is not a candidate for surgery or surgery has not been curative | Operative or consult note, or the prescriber's attestation | Cigna Signifor policy |
| Prescriber | Prescribed by or in consultation with an endocrinologist or a physician who specializes in the treatment of Cushing's syndrome | Specialty on the request, or the consult note | Cigna Signifor policy |
| Initial approval | 4 months for Cushing disease | Calendar the renewal request before month 4 | Cigna Signifor policy |
| Continuation | 1 year if the patient is currently receiving Signifor or Signifor LAR, has had a response as determined by the prescriber, and is continuing therapy to maintain response | UFC results and a note on clinical response | Cigna Signifor policy |
| Other use listed by the policy | Endogenous Cushing's syndrome, including patients awaiting surgery or a response after radiotherapy, approved for 1 year under Other Uses with Supportive Evidence. This is outside the labeled indication | Diagnosis and the surgery or radiotherapy plan | Cigna Signifor policy |
| Samples | Receipt of sample product does not satisfy any criteria requirements for coverage | Fill history rather than sample records | Cigna Signifor policy |
| Signifor LAR, Cushing disease | Separate policy IP0165: not a candidate for surgery or surgery not curative, and an endocrinologist or a physician who specializes in the treatment of Cushing's disease. 4 months initial, then 1 year if the patient has responded; no age criterion for this indication | Same chart elements; the policy gives a decrease in mean UFC as an example of response | Cigna Signifor LAR policy |
| Signifor LAR dosing limit | Up to 40mg intramuscularly no more frequently than once every 28 days for Cushing disease; billed under HCPCS J2502 | Dose and interval on the prescription | Cigna Signifor LAR policy |
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Signifor dosing and titration
| When | Label | Source |
|---|---|---|
| Signifor, start and range | 0.6mg or 0.9mg subcutaneously twice daily to start; recommended range 0.3mg to 0.9mg twice daily. Titrate on response and tolerability. | Signifor label |
| Signifor, titration | From 0.6mg twice daily, an increase to 0.9mg twice daily may be considered if 0.6mg is well tolerated. For suspected adverse reactions, temporary reduction by 0.3mg decrements per injection is suggested. | Signifor label |
| Signifor, response | Evaluate for a clinically meaningful reduction in 24-hour UFC and/or improvement in signs or symptoms; continue as long as benefit is derived. Maximum UFC reduction is typically seen by 2 months. The label sets no stopping rule for non-response. | Signifor label |
| Signifor, trial result | At Month 6, 15% (0.6mg twice daily) and 26% (0.9mg twice daily) had normalized mean UFC without a dose increase. Dose increases appeared to have minimal effect on UFC response. | Signifor label |
| Signifor, hepatic and renal | Child-Pugh B: start 0.3mg twice daily, maximum 0.6mg twice daily. Child-Pugh C: avoid. Child-Pugh A and renal impairment: no adjustment. | Signifor label |
| Signifor, missed dose | Give the next injection at the scheduled time; do not double doses. | Signifor label |
| Signifor, supply and storage | Single-dose 1mL ampules of 0.3mg/mL, 0.6mg/mL and 0.9mg/mL, box of 60 as 10 packs of 6 (NDC 55292-131-60, 55292-132-60, 55292-133-60). A box covers 30 days at twice daily dosing. Store at 25 C (77 F), excursions 15 C to 30 C, protect from light. | Signifor label |
| Signifor LAR, start | 10mg intramuscularly once every 4 weeks (every 28 days) for Cushing disease. | Signifor LAR label |
| Signifor LAR, titration | After 4 months at 10mg, the dose may be increased for patients who have not normalized 24-hour UFC and who tolerate the dose, up to a maximum of 40mg once every 28 days. | Signifor LAR label |
| Signifor LAR, over-response or adverse reactions | May require reduction to the previous tolerated dose, interruption or discontinuation; at 10mg, the dose may be interrupted or discontinued. Over-response is described as cortisol below, or in the low part of, the normal range with symptoms suggestive of adrenal insufficiency. | Signifor LAR label |
| Signifor LAR, trial result | At Month 7, mUFC response was 39.2% (10mg start) and 40.8% (30mg start), with or without up-titration at Month 4; 41.9% and 36.8% were up-titrated at Month 4. | Signifor LAR label |
| Signifor LAR, hepatic and renal | Child-Pugh B: start 10mg every 4 weeks, maximum 20mg every 4 weeks. Child-Pugh C: avoid. Child-Pugh A and renal impairment: no adjustment. | Signifor LAR label |
| Signifor LAR, missed dose | May be given up to, but no later than, 14 days prior to the next dose. | Signifor LAR label |
| Signifor LAR, supply and storage | Single-use kits of 10mg, 20mg, 30mg, 40mg and 60mg with 2mL diluent, vial adapter and a 20G x 1.5 inch safety needle (10mg kit NDC 55292-139-01). One kit per 28-day dose. Store at 2 C to 8 C (36 F to 46 F); do not freeze. | Signifor LAR label |
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Monitoring the Signifor label requires
| When | What | What the label says to do with it | Source |
|---|---|---|---|
| Signifor, glucose | Weekly for the first 2 to 3 months and periodically thereafter; again over the first 2 to 4 weeks after any dose increase | Start or adjust anti-diabetic treatment; if uncontrolled hyperglycemia persists, reduce the dose or discontinue. Poor glycemic control (HbA1c above 8%) may carry a higher risk of severe hyperglycemia and complications such as ketoacidosis. Hyperglycemia 40% and diabetes mellitus 18% in the Phase III study; mean HbA1c rose from 5.8% to 7.2% and 7.3% at Month 6 | Signifor label |
| Signifor LAR, glucose | Weekly for the first 3 months and the first 4 to 6 weeks after dose increases, then as clinically appropriate | Hyperglycemia 47% and diabetes mellitus 27% in the Cushing disease study; postmarketing ketoacidosis with and without a diabetes history. If ketoacidosis is suspected, discontinue and promptly evaluate and treat | Signifor LAR label |
| After stopping | Glucose in patients started on anti-diabetic treatment because of pasireotide | Closer monitoring after discontinuation, especially if the anti-diabetic therapy can cause hypoglycemia | Signifor label |
| Signifor, liver tests | After 1 to 2 weeks, then monthly for 3 months, then every 6 months | Normal baseline ALT: repeat within a week for 3 to 5 times ULN, within 48 hours above 5 times ULN. Abnormal baseline ALT: repeat within a week for 3 to 5 times baseline, sooner above 5 times ULN. Use a laboratory that can provide same-day results. After interruption, measure ALT, AST, alkaline phosphatase and total bilirubin weekly, or more frequently if any value exceeds 5 times ULN (5 times baseline if baseline was abnormal). If confirmed or rising, interrupt and investigate; resume cautiously only if values normalize or nearly so and another likely cause is found. ALT or AST above 3 times ULN in 5% | Signifor label |
| Signifor LAR, liver tests | After the first 2 to 3 weeks, then monthly for 3 months, then as clinically indicated | Discontinue if signs or symptoms of clinically significant liver impairment develop; do not restart if suspected to be related. Monitor patients with increased transaminases until values return to pre-treatment levels. ALT or AST above 3 times ULN in 14% and above 5 times ULN in 5% of Cushing disease patients | Signifor LAR label |
| Signifor, ECG and electrolytes | Baseline ECG; monitoring for an effect on QTc is advisable; potassium and magnesium periodically | Use with caution with congenital long QT, significant cardiac disease, anti-arrhythmics or QT-prolonging drugs, hypokalemia or hypomagnesemia. ECG QT prolonged 6% and sinus bradycardia 6% in the Phase III study | Signifor label |
| Signifor LAR, ECG | Baseline ECG; in patients at risk, QT assessment at the time of maximum concentration, 21 days after injection; correct hypokalemia or hypomagnesemia before initiating and monitor periodically | In clinical studies, QTcF above 480ms in 6 patients and an increase above 60ms in 7; none above 500ms | Signifor LAR label |
| Bradycardia | Heart rate in patients with cardiac disease or risk factors such as high-grade heart block or bradycardic drugs | Dose adjustments of beta-blockers or calcium channel blockers, or correction of electrolyte disturbances, may be necessary | Signifor label |
| Signifor, hypocortisolism | Weakness, fatigue, anorexia, nausea, vomiting, hypotension, hyponatremia or hypoglycemia | Consider temporary dose reduction or interruption and temporary exogenous glucocorticoid replacement. Adrenal insufficiency reported in 6% | Signifor label |
| Signifor LAR, adrenal insufficiency | Signs and symptoms of adrenal insufficiency; adrenal function as part of pituitary monitoring | If suspected, confirm and treat with exogenous glucocorticoids at replacement doses. Adrenal insufficiency 7% and blood cortisol decreased 5% in the Cushing disease study | Signifor LAR label |
| Signifor, gallbladder | Ultrasound before and periodically during Signifor | Cholelithiasis 30% (Signifor Phase III). If complications of cholelithiasis are suspected, discontinue and treat appropriately | Signifor label |
| Signifor LAR, gallbladder | Periodic monitoring; section 17 says by ultrasound | Cholelithiasis 33% in the Cushing disease study; discontinue if complications are suspected | Signifor LAR label |
| Pituitary function | TSH and free T4, GH and IGF-1 before and periodically during Signifor, as clinically appropriate | Higher risk after transsphenoidal surgery and pituitary irradiation | Signifor label |
| Steatorrhea | New or worsening steatorrhea, stool discoloration, loose stools, abdominal bloating, weight loss | Evaluate for pancreatic exocrine insufficiency and manage accordingly (added 7/2024) | Signifor label |
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Signifor drug interactions and contraindications
| Label category | Agents and what the label says | Source |
|---|---|---|
| QT-prolonging drugs | May have additive effects on QT prolongation; caution is required when coadministering with Signifor. | Signifor label |
| QT-prolonging drugs with Signifor LAR | Monitoring effects on the QT interval at 21 days is recommended. | Signifor LAR label |
| Cyclosporine | Pasireotide may decrease the relative bioavailability of cyclosporine; cyclosporine dose adjustment to maintain therapeutic levels may be necessary. | Signifor label |
| Bromocriptine | Somatostatin analogs may increase bromocriptine blood levels; dose reduction of bromocriptine may be necessary. | Signifor label |
| Beta-blockers, calcium channel blockers | Dose adjustments may be necessary because of bradycardia; correct electrolyte disturbances. | Signifor label |
| Anti-diabetic agents | Initiate or adjust per standard of care for hyperglycemia. After Signifor LAR is discontinued, more frequent glucose monitoring and anti-diabetic dose adjustment may be needed to mitigate hypoglycemia. | Signifor LAR label |
| Pregnancy, lactation, fertility | Limited human data are insufficient to inform risk. Discuss the potential for unintended pregnancy with premenopausal women, because lowering cortisol may improve fertility. Weigh breastfeeding benefits against the mother's need for treatment; no human milk data. | Signifor label |
| Pediatric and geriatric use | Safety and effectiveness are not established in pediatric patients. Dose selection in the elderly should be cautious, usually starting at the low end of the range. | Signifor label |
| Approval history | Drugs@FDA lists Signifor (NDA 200677) as approved December 14, 2012 and Signifor LAR (NDA 203255) as approved December 15, 2014, with an efficacy supplement for the LAR approved June 29, 2018. The latest labeling supplement listed for each product was approved July 11, 2024. | Drugs@FDA record |
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Why a first fill stalls, and the fix
- Prior authorization pending or deniedCigna asks for age 18 or older and a prescriber's statement that surgery is not an option or was not curative. It also wants an endocrinologist or a physician who specializes in treating Cushing syndrome. The endocrinologist's office sends the request and any records the plan asks for.
- The first approval ran out after 4 monthsCigna's first approval of Signifor for Cushing disease lasts 4 months. It then approves 1 year when the prescriber says there has been a response and treatment continues to maintain it. The office sends that renewal request before the first approval ends.
- Signifor LAR is reviewed under a different policyCigna reviews Signifor LAR under its own policy, with a 4-month first approval for Cushing disease as well. That policy approves up to 40mg no more often than once every 28 days. It gives a drop in urine cortisol as an example of a response at renewal.
- The prescription did not reach the right pharmacyRecordati's form says the referral is valid only if the prescriber faxes it directly to Anovo. The same form covers both Signifor and Signifor LAR prescriptions. Questions about the form or the shipment go to the number on it, 888-855-7273.
- Coverage lapses or changes during treatmentRecordati's prescriber page for Signifor LAR lists financial assistance during insurance gaps. It says this helps patients start or remain on therapy if an access or insurance gap arises. The page also lists a Patient Assistance Program for indigent patients.
- A copay you cannot payWith commercial insurance, Recordati offers a $20 co-pay for qualified patients, and eligibility rules apply. Its R.A.R.E. team also helps people identify other financial assistance opportunities. Our help paying page lists charity funds that may cover Cushing syndrome costs.
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R.A.R.E. Patient Support Program (Recordati Rare Diseases, with its specialty pharmacy)
1-888-855-7273
Monday to Friday, 8 AM to 8 PM Eastern, per Signifor.com, which adds that a pharmacist is always available (the Signifor LAR site's contact section says 9 AM to 6 PM Eastern)
- A $20 co-pay for qualified patients with commercial insurance, with eligibility requirements, restrictions and limitations
- Support for prior authorization and appeals, and a check of insurance benefits
- Help identifying other financial assistance opportunities
- Patient assistance for eligible patients who lack insurance and meet certain financial requirements
- A dedicated R.A.R.E. Nurse Educator, and extra injection training from a nurse if giving Signifor is difficult
- An optional Patient Liaison for disease education and resources, at no additional cost
- For Signifor LAR, a home injection program where a registered nurse gives the shot, at no cost to you or your insurance provider Signifor LAR patient support
- Financial assistance during insurance gaps, to help patients start or remain on therapy Signifor LAR HCP support
- Syringes, needles, alcohol pads and a sharps container sent with Signifor, unless the prescriber marks no supplies Prescription form
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Questions prescribers' offices ask about Signifor
What are the starting doses of Signifor and Signifor LAR in Cushing disease?
Signifor starts at 0.6mg or 0.9mg subcutaneously twice daily, within a range of 0.3mg to 0.9mg twice daily, per the label revised July 2024 (section 2.1). Signifor LAR starts at 10mg intramuscularly once every 4 weeks, per its own label revised July 2024 (section 2.3). After 4 months at 10mg, the LAR dose may be increased up to a maximum of 40mg every 28 days if 24-hour UFC has not normalized and the dose is tolerated.
What baseline tests do the pasireotide labels list?
Both labels, each revised July 2024, list 6 baseline tests: fasting plasma glucose, HbA1c, liver tests, an ECG, serum potassium and serum magnesium (Signifor section 2.2, Signifor LAR section 2.1). Signifor section 2.2 adds a baseline gallbladder ultrasound; the LAR label names the ultrasound in its Patient Information and section 17. Both ask for pituitary function to be checked before and periodically during treatment.
How often is glucose monitored on pasireotide?
Every week for the first 2 to 3 months on Signifor, and for the first 2 to 4 weeks after any dose increase, per the label revised July 2024 (section 5.2). The Signifor LAR label, revised July 2024, says weekly for the first 3 months and for the first 4 to 6 weeks after dose increases (section 5.1). If hyperglycemia cannot be controlled despite treatment, both labels say to reduce the dose or discontinue.
Does Signifor or Signifor LAR have a REMS?
No. Neither label, each revised July 2024, has a REMS, a boxed warning or a contraindication, and the 3 FDA approval letters reviewed (December 2012, June 2018 and July 2024) set none. Recordati's prescriber page says all prescriptions are filled through its specialty pharmacy network, and the prescription form is faxed to Anovo.
What do insurers ask for to approve Signifor?
The Cigna policy shown here, IP0482, effective May 1, 2026, approves 4 months of initial therapy for Cushing disease with 3 criteria. They are age 18 or older, a prescriber statement that the patient is not a candidate for surgery or surgery was not curative, and an endocrinologist or Cushing syndrome specialist. Continuation is approved for 1 year when the prescriber reports a response. Signifor LAR falls under a separate Cigna policy, IP0165.
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Sources
- SIGNIFOR- pasireotide injection: prescribing information, Medication Guide and Instructions for Use, revised 7/2024, Recordati Rare Diseases, Inc., via DailyMed, 2026-02-17.
- SIGNIFOR LAR- pasireotide kit: prescribing information and Patient Information, revised 7/2024, Recordati Rare Diseases, Inc., via DailyMed, 2024-07-16.
- What is SIGNIFOR and How Does it Work, Recordati Rare Diseases Inc., 2026-11-12.
- Patient - Cushing's Disease - Access and Support - SigniforLar, Recordati Rare Diseases Inc., 2026-11-12.
- HCP - Cushing's Disease - Patient Access and Support - SigniforLar HCP, Recordati Rare Diseases Inc., 2026-11-12.
- Signifor & Signifor LAR (pasireotide) Patient Prescription Form, Signifor.RX.187, effective December 1, 2020, Recordati Rare Diseases Inc. and AnovoRx, 2020-12-01.
- Drug Coverage Policy IP0482, Signifor (Cushing's, Signifor), Cigna, 2026-05-01.
- Drug Coverage Policy IP0165, Signifor LAR (Somatostatin Analogs, Signifor LAR), Cigna, 2026-05-01.
- Drugs@FDA records for NDA 200677, Signifor, and NDA 203255, Signifor LAR Kit, via openFDA, FDA, 2026-11-12.
- NDA 203255/S-011 supplement approval letter, steatorrhea, malabsorption of dietary fat and pancreatic exocrine insufficiency, FDA, 2024-07-11.
- NDA 203255/S-004 supplement approval letter, new indication for Cushing's disease and 10 mg and 30 mg strengths, FDA, 2018-06-29.
- NDA 200677 approval letter, Signifor (pasireotide) injection, for subcutaneous use, FDA, 2012-12-14.
Screen a patient against open trialsWhen to suspect Cushing disease and what to testThe patient's version of this page
A reference drawn from the February 17, 2026 label, the drugmaker's published program and one public insurer policy shown as an example, checked on November 12, 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.