Prescribing guide
Onpattro (patisiran)For hATTR polyneuropathy: weight-based dosing, premedication, infusion reactions, vitamin A and prior authorization criteriaFor prescribers and their offices treating hereditary ATTR amyloidosis with polyneuropathy: 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 and no boxed warning. A Start Form to Alnylam Assist signed by patient and prescriber; prior authorization; an infusion site, or home administration where the prescriber recommends it and the plan covers it; premedication at least 60 minutes before each infusion.
Example PA threshold
Cigna example: age 18 or older, transthyretin pathogenic variant on genetic testing, symptomatic polyneuropathy, no liver transplant history, neurologist, geneticist or amyloidosis specialist, no concurrent Amvuttra, Attruby, Tegsedi, Wainua or tafamidis.
Monitoring
No labs required by the label; monitor for IRRs during every infusion and after it if clinically indicated; vitamin A at the RDA, not titrated to serum levels; ophthalmology referral for ocular symptoms such as night blindness.
Support line
Alnylam Assist, 1-833-256-2748, 8 AM to 6 PM, Monday to Friday; a Case Manager within 2 business days of the Start Form, a commercial copay program with an annual cap, a Bridge Program for a change or delay in coverage, and a PAP mainly for the uninsured.
Give your patient their plan
A one-page handout for starting Onpattro, 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/onpattroBefore 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 |
|---|---|---|
| Submit the Start Form | Patient and prescriber signatures are required before submission. Fax to 1-833-256-2747 or submit online. Section 7 takes the primary diagnosis code, the dose in mg IV every 3 weeks, the number of vials and the patient's weight in kg. The prescriber confirms the drug is prescribed for the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. | Start Form |
| Benefit verification | An Alnylam Case Manager sends a summary of benefits to the office and the patient within 2 business days of the Start Form. The Field Reimbursement Team answers coverage, coding and reimbursement questions, including the process for submitting a prior authorization; it is reached by a Start Form or through an Alnylam sales representative. | Alnylam Assist HCP coverage |
| Choose a site of care | After a Start Form, a Case Manager works with the office and patient to help align on a site of care. The Field Reimbursement Team can provide education on selecting a treatment site, and Alnylam links to a treatment site locator. | Alnylam Assist HCP coverage |
| Home administration | Alnylam's guide says home administration may be an option for some patients after an evaluation and recommendation by the treating physician, and may not be covered by all plans. Some physicians give the first few infusions in the clinic first. In any setting, a healthcare professional performs the infusion. The label is silent on home infusion. | Dosing and Preparation Guide |
| Acquisition | Alnylam's Product Characteristics sheet lists specialty pharmacies Accredo, CVS Specialty, Orsini and PANTHERx, and specialty distributor McKesson Specialty or McKesson Plasma and Biologics. NDC 71336-1000-1, one 10mg/5mL single-dose vial per carton. The sheet, copyright 2023, lists a WAC of $9,785 per vial; confirm the current price. | Product Characteristics |
| Filters and supplies | A 0.45 micron PES syringe filter for preparation and a DEHP-free line with a 1.2 micron PES in-line filter for infusion. Alnylam's guide lists ordering options through McKesson and some specialty pharmacies; filter cost through McKesson is the provider's responsibility. | Dosing and Preparation Guide |
| Coverage gap | The Alnylam Assist Bridge Program provides medication for eligible Onpattro patients who experience a change or delay in coverage. A Case Manager determines eligibility after a Start Form. | Alnylam Assist HCP |
| Copay program terms | Commercial insurance only, with an annual benefit cap; the patient pays once the cap is reached in a calendar year. Not valid under Medicare, Medicaid, TRICARE, VA, DoD, IHS or other federal or state programs, or when the product is not covered. Its terms say the value is meant to count toward patient out-of-pocket obligations, including under accumulator or maximizer programs. Patients 18 or older; pharmacist questions go to CapitalRx at 1-844-306-9173. | Copay terms |
| Counsel on infusion reactions | Inform patients of the signs the label lists (flushing, dyspnea, chest pain, syncope, rash, increased heart rate, facial edema) and advise them to contact their healthcare provider immediately if they occur. | FDA label |
| Counsel on vitamin A | Instruct the patient to take the RDA of vitamin A and to report ocular symptoms such as night blindness. The label gives no start day for the supplement. | FDA label |
| Pregnancy | No data in pregnant women. In rabbits, embryofetal mortality and reduced fetal body weight occurred at doses that were also maternally toxic; no adverse developmental effects were seen in rats. The label asks patients to report pregnancy or plans for it, advises counseling females of childbearing potential on potential fetal risk, and notes that both vitamin A deficiency and excess affect embryofetal development. Pregnancy exposure registry: 1-877-256-9526. Lactation: no information on presence in human milk, effects on the breastfed infant or milk production; in lactating rats patisiran was not detected in milk, but the lipid components were. | FDA label |
Prior authorization criteria and what to document
One public policy as the example: Cigna, March 1, 2026. Approval approval lasts a year at a time, and the policy lists no separate renewal criteria. This policy took effect on March 1, 2026, and cites the January 2023 version of the label. The current label is dated September 2025, with the same indication and dose. The ban on combining TTR medicines and the liver transplant rule are the plan's rules, not the label's. 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 |
|---|---|---|---|
| Diagnosis | Polyneuropathy of hereditary transthyretin-mediated amyloidosis, age 18 or older | Diagnosis note | Cigna policy |
| Genetic confirmation | Transthyretin pathogenic variant confirmed by genetic testing, documentation required | Genetic test report | Cigna policy |
| Symptomatic polyneuropathy | Documentation required. Examples: reduced motor strength or coordination, impaired sensation (pain, temperature, vibration, touch); assessed by history and clinical exam, electromyography or nerve conduction velocity testing | Exam note, EMG or nerve conduction report | Cigna policy |
| Liver transplant | No history of liver transplantation; added as a requirement in the March 1, 2026 revision | Surgical history in the note | Cigna policy |
| Prescriber | Neurologist, geneticist or a physician who specializes in the treatment of amyloidosis, prescribing or consulting | Specialty on the request | Cigna policy |
| Combination | No concurrent Amvuttra, Attruby, Tegsedi, Wainua or a tafamidis product; Cigna lists concurrent use under conditions not covered | Current medication list; a stop date if switching | Cigna policy |
| Dose | Up to 0.3mg/kg IV, maximum 30mg, no more often than once every 3 weeks; other doses reviewed case by case | Order with current weight | Cigna policy |
| Duration and coding | Approval for 1 year; no separate renewal criteria listed. HCPCS J0222, injection, patisiran, 0.1mg | Calendar the reauthorization | Cigna policy |
Onpattro dosing and titration
| When | Label | Source |
|---|---|---|
| Under 100kg | 0.3mg/kg by IV infusion once every 3 weeks, based on actual body weight, administered by a healthcare professional. | FDA label |
| 100kg or more | 30mg by IV infusion once every 3 weeks. | FDA label |
| Premedication, at least 60 minutes before | IV corticosteroid (e.g., dexamethasone 10mg or equivalent), oral acetaminophen 500mg, IV H1 blocker (e.g., diphenhydramine 50mg or equivalent), IV H2 blocker (e.g., famotidine 20mg or equivalent), on the day of infusion. Oral equivalents if IV is unavailable or not tolerated. Some patients may require additional or higher doses. | FDA label |
| Corticosteroid step-down | For patients tolerating infusions but with corticosteroid-related adverse reactions, reduce by 2.5mg increments to a minimum of 5mg dexamethasone IV, or equivalent. | FDA label |
| Preparation | Warm vials to room temperature; do not shake or vortex. Withdraw into a single syringe, filter through a 0.45 micron PES syringe filter into a sterile container, then dilute the required volume in 0.9% sodium chloride to a total of 200mL in a DEHP-free bag. Use immediately, or hold in the bag at up to 30 degrees C (86 degrees F) for up to 16 hours including infusion time. Do not freeze. | FDA label |
| Infusion | Dedicated DEHP-free line with a 1.2 micron PES in-line filter, by ambulatory infusion pump, over approximately 80 minutes: approximately 1mL/min for the first 15 minutes, then approximately 3mL/min. Free-flowing venous access only; flush the set with 0.9% sodium chloride afterward. | FDA label |
| Missed dose | Administer as soon as possible. Within 3 days of the missed dose, keep the original schedule; more than 3 days, continue every 3 weeks from that dose. | FDA label |
| Vials per dose | Alnylam's dosing table assumes 1mL of hold-up volume in the filter, so an additional vial may be needed at some weights; it shows 1 to 4 vials by weight. | Dosing and Preparation Guide |
| Storage | Vials at 2 to 8 degrees C (36 to 46 degrees F); do not freeze, and discard a vial that has been frozen. Room temperature up to 25 degrees C (77 degrees F) for up to 14 days if refrigeration is unavailable. | FDA label |
Monitoring the Onpattro label requires
| When | What | What the label says to do with it | Source |
|---|---|---|---|
| Baseline and ongoing | No laboratory test required by the label | The label has no boxed warning and no contraindications | FDA label |
| Every infusion | Signs and symptoms of IRRs during the infusion, and after it if clinically indicated | 19% of patients had IRRs vs 9% on placebo; 79% of first IRRs came within the first 2 infusions; interruption in 5%; permanent discontinuation in under 1%. Severe hypotension and syncope have been reported | FDA label |
| If an IRR occurs | Consider slowing or interrupting the infusion and medical management (e.g., corticosteroids or other symptomatic treatment) | Resume at a slower rate only if symptoms have resolved; discontinue and do not resume for a serious or life-threatening IRR. A slower rate or additional or higher premedication doses may help at later infusions | FDA label |
| Every infusion | Infusion site, for infiltration | Extravasation in under 0.5% of infusions, some serious; manage per local practice for non-vesicants | FDA label |
| Throughout | Vitamin A supplementation at the RDA | Do not dose above the RDA to normalize serum vitamin A. 64% normal at baseline, 99% of those went low; mean serum vitamin A down 62% over 18 months | FDA label |
| Any time | Ocular symptoms suggestive of vitamin A deficiency, such as night blindness | Refer to an ophthalmologist. Dry eye 5%, blurred vision 3% and vitreous floaters 2% were reported in the controlled trial | FDA label |
| Any time | Conduction | Four serious AV block reactions (2.7%), 3 complete, vs none on placebo; the label gives no monitoring instruction | FDA label |
| Pharmacodynamics | Serum TTR | Mean reduction about 80% within 10 to 14 days of a single dose; 83% and 84% at 9 and 18 months; similar regardless of prior liver transplantation | FDA label |
Onpattro drug interactions and contraindications
| Label category | Agents and what the label says | Source |
|---|---|---|
| Contraindications | None | FDA label |
| CYP enzymes and transporters | No formal clinical interaction studies. Components are not inhibitors or inducers of CYP enzymes or transporters at clinically relevant concentrations, and patisiran is not a CYP substrate. Not expected to cause or be affected by CYP-mediated interactions | FDA label |
| Other infusions | Do not mix or dilute with other drugs; use a dedicated line | FDA label |
| Vitamin A products | Supplement at the RDA only; higher doses should not be given to normalize serum levels | FDA label |
| Payer rule on combinations | Cigna: concurrent Amvuttra, Attruby, Tegsedi, Wainua or a tafamidis product is not covered, citing a lack of controlled data for additive efficacy. The label has no statement on combination use | Cigna policy |
| Hepatic and renal impairment | No adjustment for mild hepatic impairment or mild to moderate renal impairment (eGFR 30 to under 90). Not studied in moderate or severe hepatic impairment, severe renal impairment or ESRD | FDA label |
| Immunogenicity | Anti-drug antibodies in 7 of 194 patients (3.6%); no evidence of an effect on efficacy, safety, PK or PD, with limited data | FDA label |
Why a first fill stalls, and the fix
- Prior authorization pending or deniedThe Case Manager keeps you updated on prior authorizations and appeals and tells you about any step you need to take. Your doctor's office and treatment site can contact Alnylam Assist for support.
- The plan wants more recordsPlans such as Cigna ask for the genetic test result and documentation of symptomatic polyneuropathy. Cigna's policy gives a clinical exam, electromyography and nerve conduction testing as examples. The neurologist's office sends these records to the plan.
- The plan will not pay alongside another TTR medicineCigna's policy does not cover Onpattro used with Amvuttra, Attruby, Tegsedi, Wainua or a tafamidis product. The neurologist's office decides whether to appeal or change the plan of treatment.
- A liver transplant in your historyCigna's policy, since March 2026, requires that the patient has no history of liver transplantation. The label reports similar TTR lowering in people with a prior liver transplant, and the neurologist's office decides whether to appeal.
- The place of the infusion is not coveredAlnylam's guide for clinicians says home infusion may not be covered by all insurance plans. It says Alnylam Assist can help answer questions about home administration.
- Your insurance changed partway throughThe Alnylam Assist Bridge Program provides medicine to eligible Onpattro patients who have a change or delay in coverage. A Case Manager checks eligibility once a Start Form is on file.
- A cost you cannot payCommercial insurance: the Alnylam Assist Copay Program, which covers certain out-of-pocket costs. People on Medicare, Medicaid or other government insurance cannot use it. The Alnylam Assist Patient Assistance Program gives treatment at no cost to eligible people, mainly the uninsured.
Alnylam Assist
- The Alnylam Assist Copay Program, which covers certain out-of-pocket costs for eligible people with commercial insurance, not for Medicare, Medicaid or other government insurance
- Programs that may help during a delay or change in insurance coverage, with eligibility set by a Case Manager after a Start Form
- The Alnylam Assist Patient Assistance Program, which provides treatment at no cost to eligible people, mainly the uninsured
- A link to independent foundations that may offer financial help to people who are uninsured or underinsured
- Alnylam Case Managers who verify your benefits, check whether you qualify for financial help and schedule check-ins before and after each treatment, once your doctor sends a Start Form Alnylam Assist teams
- Patient Education Liaisons, Alnylam employees with nursing backgrounds who teach about the disease and answer treatment questions but do not give medical care or advice Alnylam Assist teams
- The copay program has an annual cap, and its terms require a patient to be 18 or older with a valid prescription Copay terms
Questions prescribers' offices ask about Onpattro
What is the Onpattro dose?
The September 2025 label sets 0.3mg/kg by intravenous infusion once every 3 weeks for patients under 100kg, and 30mg once every 3 weeks at 100kg or more, based on actual body weight. No dose adjustment is required for age 65 or older, mild or moderate renal impairment, or mild hepatic impairment.
What premedication does Onpattro require?
Four agents at least 60 minutes before the start of each infusion, per the September 2025 label: an IV corticosteroid (for example dexamethasone 10mg), oral acetaminophen 500mg, an IV H1 blocker (for example diphenhydramine 50mg) and an IV H2 blocker (for example famotidine 20mg). Oral equivalents may be used when IV forms are unavailable or not tolerated, and the corticosteroid may be stepped down in 2.5mg increments to a minimum of dexamethasone 5mg IV for steroid-related adverse reactions in patients tolerating infusions.
How is the Onpattro infusion run, and what does the label say to do for an infusion-related reaction?
About 80 minutes by ambulatory infusion pump, per the September 2025 label: approximately 1mL/min for the first 15 minutes, then approximately 3mL/min. For an IRR, consider slowing or interrupting the infusion and instituting medical management; resume at a slower rate only if symptoms have resolved. A serious or life-threatening IRR means the infusion is discontinued and not resumed.
What does the label say about vitamin A on Onpattro?
Supplementation at the recommended daily allowance is advised for all patients under the September 2025 label, and higher doses should not be given to normalize serum levels, which do not reflect total body vitamin A. In the placebo-controlled study, 99% of patients with a normal baseline developed low levels, and mean serum vitamin A fell 62% over 18 months. Refer to an ophthalmologist for ocular symptoms suggestive of deficiency, such as night blindness.
What do insurers ask for to approve Onpattro?
The Cigna policy on this page, effective March 1, 2026, approves 1 year for patients 18 or older with a transthyretin pathogenic variant confirmed by genetic testing, symptomatic polyneuropathy, and no history of liver transplantation. It requires a neurologist, geneticist or amyloidosis specialist, caps dosing at 0.3mg/kg up to 30mg every 3 weeks, and excludes concurrent Amvuttra, Attruby, Tegsedi, Wainua or tafamidis.
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Sources
- ONPATTRO (patisiran) lipid complex injection, for intravenous use, Revised: 9/2025, Alnylam Pharmaceuticals, via DailyMed, 2025-09-08.
- ONPATTRO® (patisiran) Dosing and Preparation Guide (TTR02-USA-00054-052018-V12), Alnylam Pharmaceuticals, 2026-11-12.
- Coverage & Starting Treatment | ONPATTRO® (patisiran) | Alnylam Assist®, Alnylam Pharmaceuticals, 2026-11-12.
- Support & Education Teams | ONPATTRO® (patisiran) | Alnylam Assist®, Alnylam Pharmaceuticals, 2026-11-12.
- Financial Assistance | ONPATTRO® (patisiran) | Alnylam Assist®, Alnylam Pharmaceuticals, 2026-11-12.
- Financial Assistance | ONPATTRO® (patisiran) | Alnylam Assist® HCP, Alnylam Pharmaceuticals, 2026-11-12.
- Coverage & Treatment Initiation | ONPATTRO® (patisiran) | Alnylam Assist® HCP, Alnylam Pharmaceuticals, 2026-11-12.
- Alnylam Assist® Copay Program Enrollment, Terms and Conditions, Alnylam Pharmaceuticals, 2026-11-12.
- Alnylam Assist® Start Form, ONPATTRO® (patisiran) (TTR02-USA-00162-V7), Alnylam Pharmaceuticals, 2026-11-12.
- ONPATTRO® (patisiran) Product Characteristics (TTR02-USA-00055-032018-V6), Alnylam Pharmaceuticals, 2026-11-12.
- Drug Coverage Policy IP0418, Onpattro, Cigna, 2026-03-01.
- NDA 210922/S-012 supplement approval letter, sections 12.2 and 12.3, FDA, 2023-01-13.
- NDA 210922/S-013 supplement approval letter, section 6.1, FDA, 2022-10-03.
- NDA 210922 approval letter, FDA, 2018-08-10.
A reference drawn from the September 8, 2025 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.