Prescribing guide
Ultomiris (ravulizumab-cwvz)Meningococcal vaccine requirements, REMS, weight-based dosing, switching from eculizumab and prior authorization criteria for PNHFor prescribers and their offices treating paroxysmal nocturnal hemoglobinuria (PNH): what the pharmacy needs before it ships, what the prior authorization wants documented, the titration and the monitoring the label requires.
Dispensing gate
REMS-certified prescriber, MenACWY and MenB vaccination completed or updated at least 2 weeks before day 1 or antibacterial prophylaxis with vaccines as soon as possible, counseling with the Patient Safety Card and Patient Guide, and a REMS-certified healthcare setting or pharmacy that verifies prescriber certification and documents vaccination status.
Example PA threshold
Label: adult and pediatric patients 1 month of age and older with PNH, dosing from 5kg. FEP example: age 1 month or older, documented baseline serum LDH, no dual therapy with another prior authorization medication for PNH, meningococcal vaccination at least 2 weeks before initiation unless treatment cannot be delayed, prescriber enrolled in the REMS.
Monitoring
Meningococcal infection at any time, at least 1 hour of observation after each infusion, revaccination per ACIP for the duration of therapy, and at least 16 weeks of monitoring for hemolysis after discontinuation; no scheduled on-treatment laboratory test is written into the label for PNH.
Support line
Alexion OneSource, 1-888-765-4747, Monday to Friday 8:30 AM to 8 PM ET, CoPay Program as little as $0 for commercial plans, annual maximums may apply, enrollment fax 1-800-420-5150; the label lists the same number for the REMS.
Give your patient their plan
A one-page handout for starting Ultomiris, 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/ultomiris-paroxysmalBefore 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 |
|---|---|---|
| Certify in the ULTOMIRIS and SOLIRIS REMS | Review the Prescribing Information, Healthcare Provider Safety Brochure, Patient Safety Card and Patient Guide, then submit the Prescriber Enrollment Form to the REMS. | FDA REMS page |
| Assess before initiation | Assess for unresolved meningococcal infection and do not initiate if a serious one is unresolved. Assess vaccination status for serogroups A, C, W, Y and B and vaccinate as needed per current ACIP recommendations for complement inhibitor recipients. | FDA REMS page |
| Vaccinate | Complete or update vaccination against Neisseria meningitidis serogroups A, C, W, Y and B at least 2 weeks before the first dose. ACIP's schedule for these patients differs from the vaccine prescribing information, so prior standard vaccination may not meet it. | FDA label |
| Or prophylaxis | If urgent therapy is indicated in a patient not up to date, give antibacterial prophylaxis and the vaccines as soon as possible; the REMS requires the prescriber to write the prophylaxis prescription. The label says optimal regimens and durations have not been studied. | FDA label |
| Pneumococcal and Hib | Section 5.3 says children treated with Ultomiris may be at increased risk of serious S. pneumoniae and Hib infections and says to vaccinate against both per ACIP. The Medication Guide tells parents a treated child should receive these vaccines. Not a REMS element. | FDA label |
| Counsel and hand over the card | Counsel with the Patient Safety Card and Patient Guide and give the patient copies. The card is carried at all times during treatment and for 8 months after the last Ultomiris dose. | FDA REMS page |
| Book a certified site | Healthcare settings and pharmacies that dispense must be certified. Before each dispense they contact the REMS to verify the prescriber is certified. Before the first dose they assess and document meningococcal vaccination status, including prophylaxis if needed, and repeat that for up to 6 months in patients not initially up to date. | FDA REMS page |
| Contraindication | Do not initiate in a patient with unresolved serious Neisseria meningitidis infection. This is the label's only contraindication. | FDA label |
| OneSource enrollment | Online form, email to OneSource@Alexion.com or fax to 1-800-420-5150, signed by the patient or a legal representative. The form lists PNH as a condition; interpreters are available. | OneSource enrollment |
| Vaccination support | For patients signed up with OneSource and prescribed meningococcal vaccines: support locating a vaccination site, information on resources that may cover vaccination costs, and vaccine tracking resources. | OneSource vaccination support |
| Access tools | Alexion Access Navigator posts a Prior Authorization Checklist for PNH, a PNH sample letter of medical necessity, a PNH sample appeal letter, a PNH coding and billing guide, a peer-to-peer review resource, a reauthorization guide and home infusion access considerations. Field Reimbursement Managers are reached through 1-888-765-4747. | Alexion Access Navigator |
| CoPay Program | Commercial insurance only, enrolled in OneSource, FDA-approved indication, US or territories; as little as $0, annual maximums may apply. Excludes Medicare, Medicare Advantage, Medigap, Medicaid, VA, DoD and TRICARE. Massachusetts and Rhode Island residents get medication but not infusion cost help. | CoPay terms |
Prior authorization criteria and what to document
One public policy as the example: Blue Cross Blue Shield Federal Employee Program, July 1, 2026. Approval six months at first, then 12 months at a time on renewal. Renewal asks for a decrease in serum LDH from the pretreatment baseline, no unacceptable toxicity and continued REMS enrollment. This policy was approved on June 11, 2026 and cites the September 2025 label. It predates the October 2026 label, which added IgA nephropathy as a use. The PNH use it describes matches the current label. It still uses the old program name, Ultomiris REMS, from before March 2024. 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 | Paroxysmal nocturnal hemoglobinuria, 1 month of age or older | Diagnosis in the note | FEP Blue policy |
| Baseline LDH | Documented baseline value for serum lactate dehydrogenase (LDH) | Pretreatment LDH with date; it is the comparator at renewal | FEP Blue policy |
| No dual therapy | No dual therapy with another prior authorization medication for PNH; Appendix 1 lists Soliris, Fabhalta, Empaveli and Ultomiris | Medication list; for a switch, the last eculizumab dose date | FEP Blue policy |
| Vaccination | Vaccination against Neisseria meningitidis at least 2 weeks prior to initiation, unless treatment cannot be delayed | Vaccine names and dates, or the prophylaxis prescription | FEP Blue policy |
| REMS | Prescriber enrolled in the REMS; the policy still uses the old name Ultomiris REMS | Enrollment confirmation | FEP Blue policy |
| Approval duration | Six months initially, 12 months on renewal; the policy cites the September 2025 package insert | Calendar the renewal ahead of the dose that follows month 6 | FEP Blue policy |
| Renewal | Decrease in serum LDH from pretreatment baseline, absence of unacceptable toxicity, no dual therapy, prescriber still enrolled in the REMS | LDH trend since start | FEP Blue policy |
| Trial population, naive | Study ALXN1210-PNH-301 randomized 246 complement inhibitor-naive adults with active hemolysis and at least 5% PNH cells by flow cytometry; registered as NCT02946463 | Flow cytometry, LDH and transfusion history, for a letter of medical necessity | ClinicalTrials.gov, Study 301 |
| Trial population, switch | Study ALXN1210-PNH-302 randomized 195 adults clinically stable on eculizumab for at least the past 6 months; registered as NCT03056040 | Eculizumab start date and recent LDH, for a switch request | ClinicalTrials.gov, Study 302 |
| Trial population, pediatric | Study ALXN1210-PNH-304 treated 13 pediatric patients, 5 complement inhibitor-naive and 8 eculizumab-experienced, aged 9 to 17; registered as NCT03406507 | Age, weight and prior eculizumab, for a pediatric request | ClinicalTrials.gov, Study 304 |
Ultomiris dosing and titration
| When | Label | Source |
|---|---|---|
| Day 1, loading | 5 to under 10kg: 600mg. 10 to under 20kg: 600mg. 20 to under 30kg: 900mg. 30 to under 40kg: 1,200mg. 40 to under 60kg: 2,400mg. 60 to under 100kg: 2,700mg. 100kg or more: 3,000mg. Minimum infusion 1.4, 0.8, 0.6, 0.5, 0.8, 0.6 and 0.4 hours; maximum rate 9, 15, 30, 48, 60, 90 and 150mL/hr respectively (Table 4). | FDA label |
| Day 15, first maintenance | 300mg, 600mg, 2,100mg, 2,700mg, 3,000mg, 3,300mg or 3,600mg by the same weight bands; minimum infusion 0.8, 0.8, 1.3, 1.1, 0.9, 0.7 and 0.5 hours, maximum rate 8, 15, 33, 50, 67, 95 and 144mL/hr (Table 5). The 7-day window does not apply to this dose. | FDA label |
| Maintenance interval | Every 4 weeks from 5kg to under 20kg; every 8 weeks at 20kg or more, counted from day 15. Occasional variation within 7 days of the scheduled day is allowed; subsequent doses return to the original schedule. | FDA label |
| Weight changes | Tables 4 and 5 are read by body weight at the time of treatment, so a growing child can cross into a new band and interval. | FDA label |
| Switching from eculizumab | Loading dose at the time of the next scheduled eculizumab dose; first maintenance dose 2 weeks after the loading dose (Table 2). | FDA label |
| Route | Section 2.1: intended to be administered only as an intravenous infusion. Dilute to 50mg/mL in 0.9% sodium chloride and give through a 0.2 or 0.22 micron filter. | FDA label |
| After PE, PP or IVIg | Supplemental dose within 4 hours after each PE or PP session (1,200mg to 1,800mg by weight and most recent dose) or after completion of an IVIg cycle (600mg). Table 3 lists weight bands of 40kg or more only. | FDA label |
| Missed dose | The patient should contact the healthcare provider immediately. | FDA label |
| Preparation and stability | Administer immediately after dilution. If not, refrigerate at 2 to 8°C for no more than 24 hours including infusion time, then give within 4 hours of removal. Let the admixture reach room temperature in ambient air only. | FDA label |
| Vials | 300mg/3mL (NDC 25682-025-01) and 1,100mg/11mL (NDC 25682-028-01) single-dose vials, one per carton; refrigerate at 2 to 8°C in the carton, do not freeze or shake. | FDA label |
| Pediatric and geriatric | Established for PNH from 1 month of age; use under 9 years and under 30kg rests on extrapolated PK/PD, efficacy and safety data from aHUS and PNH studies. The PNH studies included 58 patients aged 65 or older, too few to assess differences. | FDA label |
Monitoring the Ultomiris label requires
| When | What | What the label says to do with it | Source |
|---|---|---|---|
| Before day 1 | Meningococcal vaccination status against the ACIP complement inhibitor schedule; unresolved serious N. meningitidis infection | Required by the label and the REMS; prophylaxis prescription if urgent; initiation contraindicated with unresolved serious infection | FDA label |
| Each infusion | Infusion-related reactions: lower back or abdominal pain, muscle spasms, drop or rise in blood pressure, rigors, limb discomfort, hypersensitivity, dysgeusia; anaphylaxis reported postmarketing | Observe at least 1 hour after completion; slow or stop at the physician's discretion, interrupt for cardiovascular instability or respiratory compromise. Reported in about 1 to 8% across trials, 1% in the adult PNH trials | FDA label |
| Any time | Meningococcal infection: fever, fever with tachycardia, headache with fever, confusion, myalgia with flu-like symptoms, fever with rash, headache with nausea or vomiting, headache with stiff neck or back, photophobia | Evaluate immediately; consider interrupting Ultomiris during treatment of serious meningococcal infection, weighing the risk of interruption in the disease being treated | FDA label |
| Per ACIP | Meningococcal revaccination | Revaccinate considering the duration of therapy; vaccination does not eliminate risk | FDA label |
| Ongoing | Other Neisseria and encapsulated bacterial infections, including disseminated gonococcal infection | Use caution with any other systemic infection; counsel on gonorrhea prevention and regular testing for patients at risk | FDA label |
| After discontinuation | Hemolysis: elevated LDH with a sudden decrease in PNH clone size or hemoglobin, or return of fatigue, hemoglobinuria, abdominal pain, dyspnea, major adverse vascular event including thrombosis, dysphagia or erectile dysfunction | Monitor for at least 16 weeks; if signs of hemolysis occur, including elevated LDH, consider restarting Ultomiris. Patient Safety Card and no breastfeeding for 8 months after the last dose | FDA label |
| Adult PNH safety | Upper respiratory tract infection 39% (eculizumab 39%), headache 32% (26%), diarrhea 9% (5%), nausea 9% (9%), pyrexia 7% (8%), abdominal pain 6% (7%), pain in extremity 6% (5%), arthralgia 5% (5%), dizziness 5% (6%) | 222 adults on Ultomiris and 219 on eculizumab, median 6 months; serious adverse reactions in 15 patients (6.8%); 1 fatal case of sepsis | FDA label |
| Pediatric PNH safety | Upper respiratory tract infection 54%, anemia 23%, abdominal pain 23%, headache 23%, constipation 15%, pyrexia 15%, pain in extremity 15% | 13 patients aged 9 to 17 in Study ALXN1210-PNH-304; profile similar to adults | FDA label |
| Study 301 efficacy | Transfusion avoidance 73.6% against 66.1% on eculizumab; LDH normalization 53.6% against 49.4%; breakthrough hemolysis 4.0% against 10.7%; hemoglobin stabilization 68.0% against 64.5% | 26 weeks, open label, non-inferiority shown across endpoints; 125 on Ultomiris, 121 on eculizumab | FDA label |
| Study 302 efficacy | LDH percent change -0.82% against 8.4% on eculizumab; breakthrough hemolysis 0% against 5.1%; transfusion avoidance 87.6% against 82.7%; hemoglobin stabilization 76.3% against 75.5% | 26 weeks, open label, non-inferiority shown across endpoints; 97 switched to Ultomiris, 98 continued eculizumab | FDA label |
| Study 304 efficacy | Transfusion avoidance in 11 of 13 over 26 weeks; hemoglobin stabilization in 3 of 5 naive and 6 of 8 eculizumab-experienced patients; no breakthrough hemolysis in the primary period | One breakthrough hemolysis event at 1.8 years in the extension, with free C5 under 0.5mcg/mL | FDA label |
Ultomiris drug interactions and contraindications
| Label category | Agents and what the label says | Source |
|---|---|---|
| Plasma exchange, plasmapheresis, IVIg | Reduce serum ravulizumab concentrations and require a supplemental dose within 4 hours (Table 3) | FDA label |
| Neonatal Fc receptor blockers | Agents such as efgartigimod may lower systemic exposure and reduce effectiveness; closely monitor for reduced effectiveness | FDA label |
| Anticoagulants | The effect of withdrawing anticoagulant therapy during treatment has not been established; treatment should not alter anticoagulant management | FDA label |
| Pregnancy and lactation | No human data; PNH in pregnancy is associated with adverse maternal and fetal outcomes; registry 1-833-793-0563; human IgG crosses the placenta; discontinue breastfeeding during treatment and for 8 months after the final dose | FDA label |
| Contraindicated | Initiation in patients with unresolved serious Neisseria meningitidis infection | FDA label |
Why a first fill stalls, and the fix
- Prior authorization pending or deniedThe FEP policy below asks for age 1 month or older and a baseline LDH value on record. It also asks that no other PNH drug on its prior authorization list is used at the same time. That list names Soliris, Fabhalta, Empaveli and Ultomiris. Your hematologist's office sends the records that show each of these points.
- Your vaccine dates are missingThe REMS requires the infusion site or pharmacy to check and record your meningococcal vaccine status before the first dose. The fix is the office sending the vaccine dates, or the antibiotic prescription if treatment cannot wait.
- The infusion site is not certifiedOnly healthcare settings and pharmacies certified in the ULTOMIRIS and SOLIRIS REMS may dispense it. The office moves the booking to a certified site, which makes it a routing problem and not a denial.
- The prescriber is not enrolled in the REMSBefore each dispense, the site must contact the REMS to confirm the prescriber is certified. A prescriber enrolls by completing the Prescriber Enrollment Form and sending it to the REMS.
- The plan says no after reviewAlexion Access Navigator posts a PNH sample letter of medical necessity and a PNH sample appeal letter for your hematologist's office. It also posts a guide to peer-to-peer reviews, which it describes as a step before a formal appeal.
- A copay you cannot payWith commercial insurance, the OneSource CoPay Program can bring the cost as low as $0 for eligible patients. Medicare, Medicaid and other government plans are excluded, and OneSource says it can connect those patients with third-party resources.
- You live in Massachusetts or Rhode IslandThe CoPay terms say residents of these 2 states can get help with medicine costs but not with infusion costs. OneSource answers questions about the terms at 1-888-765-4747.
- The renewal after 6 monthsThe FEP policy approves 6 months at first, then 12 months at a time. Renewal asks for a serum LDH that has fallen from the level before treatment, and no unacceptable toxicity. Ask the office when the renewal is due.
Alexion OneSource
- The Alexion OneSource CoPay Program for commercial insurance, as little as $0 for Ultomiris for eligible patients
- The CoPay Program covers eligible out-of-pocket medicine and infusion costs, and annual maximums may apply CoPay terms
- CoPay help is not open to Medicare, Medicaid or other federal- or state-funded plans, and OneSource can point those patients to third-party resources
- Residents of Massachusetts and Rhode Island can get help with medicine costs but not infusion costs, under the CoPay terms CoPay terms
- Vaccination support for enrolled patients, including help locating a vaccination site and information on resources that may cover vaccine costs OneSource vaccination support
- Help understanding insurance coverage, and information on infusion centers or other treatment locations nearby About OneSource
- Enrollment online, by email to OneSource@Alexion.com or by fax at 1-800-420-5150, with interpreters available OneSource enrollment
- Questions answered by phone without enrolling OneSource enrollment
- For the hematologist's office, a Field Reimbursement Manager plus PNH sample letters for medical necessity and appeals Alexion Access Navigator
Questions prescribers' offices ask about Ultomiris
What is the Ultomiris dose for PNH?
From 5kg upward, the October 2026 label gives a weight-based IV loading dose of 600mg to 3,000mg, then a maintenance dose of 300mg to 3,600mg starting 2 weeks later. Maintenance is every 4 weeks from 5kg to under 20kg and every 8 weeks at 20kg or more. Later doses may occasionally vary within 7 days of the scheduled day, but not the first maintenance dose.
Which vaccines are required before Ultomiris?
Meningococcal vaccines against serogroups A, C, W, Y and B, completed or updated at least 2 weeks before the first dose, per the boxed warning and section 2.2 of the October 2026 label, on the ACIP schedule for complement inhibitor recipients. If urgent therapy is indicated in a patient who is not up to date, the label says to give antibacterial prophylaxis and the vaccines as soon as possible. Section 5.3 adds pneumococcal and Hib vaccination per ACIP and notes higher risk in children.
How is a patient switched from eculizumab to Ultomiris?
The weight-based Ultomiris loading dose is given at the time of the next scheduled eculizumab dose, per Table 2 of the October 2026 label. The first maintenance dose follows 2 weeks after the loading dose. In Study 302, 195 adults stable on eculizumab for at least 6 months were randomized to switch or continue; LDH percent change was -0.82% against 8.4% and breakthrough hemolysis 0% against 5.1%.
How long is a patient monitored after stopping Ultomiris for PNH?
At least 16 weeks, per section 5.4 of the October 2026 label. Monitor for hemolysis, identified by elevated LDH with a sudden decrease in PNH clone size or hemoglobin, or by the return of fatigue, hemoglobinuria, abdominal pain, dyspnea, a major adverse vascular event including thrombosis, dysphagia or erectile dysfunction. If these occur, the label says to consider restarting Ultomiris.
What do insurers ask for to approve Ultomiris for PNH?
The FEP policy shown here took effect July 1, 2026 and cites the September 2025 label. It asks for age 1 month or older, a documented baseline serum LDH, no dual therapy with another prior authorization medication for PNH, meningococcal vaccination at least 2 weeks before initiation unless treatment cannot be delayed, and REMS enrollment. It approves 6 months, then 12 months with a decrease in serum LDH from the pretreatment baseline.
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Sources
- ULTOMIRIS (ravulizumab-cwvz) injection, for intravenous use: prescribing information and Medication Guide, revised 10/2026, SPL version 20, effective October 29, 2026 (openFDA record for DailyMed set ID a9a590d9-0217-43c7-908d-e62a71279791), Alexion Pharmaceuticals, via FDA openFDA, 2026-10-29.
- Approved Risk Evaluation and Mitigation Strategies (REMS): Ultomiris and Soliris, BLA 125166 and BLA 761108, REMS last update 06/01/2026, FDA, 2026-06-01.
- Alexion OneSource™ | ULTOMIRIS | Financial Assistance, Alexion Pharmaceuticals, 2026-11-13.
- Alexion OneSource™ | ULTOMIRIS | Fill Out a Start Form, Alexion Pharmaceuticals, 2026-11-13.
- Alexion OneSource™ | ULTOMIRIS | Vaccination-Support, Alexion Pharmaceuticals, 2026-11-13.
- Alexion OneSource™ | ULTOMIRIS | About OneSource™, Alexion Pharmaceuticals, 2026-11-13.
- Alexion OneSource™ CoPay Program Terms and Conditions, US/ALL/1223 V1 12/2024, Alexion Pharmaceuticals, 2026-11-13.
- Alexion Access Navigator | Ultomiris PNH, Alexion Pharmaceuticals, 2026-11-13.
- 5.85.033 Ultomiris (ravulizumab-cwvz), Blue Cross Blue Shield Federal Employee Program, 2026-07-01.
- BLA 761108 BLA approval letter, ULTOMIRIS (ravulizumab-cwvz) for adult patients with paroxysmal nocturnal hemoglobinuria, and its REMS, FDA, 2018-12-21.
- BLA 761108/S-012 supplement approval letter, treatment of pediatric patients with paroxysmal nocturnal hemoglobinuria, FDA, 2021-06-07.
- BLA 761108/S-021 corrected supplement approval letter, subcutaneous route of administration and on-body delivery system for adults with PNH and aHUS, FDA, 2022-07-22.
- BLA 761108/S-036 supplement approval letter, removing the subcutaneous route of administration using the on-body delivery system from the Prescribing Information and Medication Guide, FDA, 2024-06-28.
- ALXN1210 (Ravulizumab) Versus Eculizumab in Complement Inhibitor Treatment-Naïve Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) (NCT02946463, Study ALXN1210-PNH-301), ClinicalTrials.gov, 2026-11-13.
- ALXN1210 Versus Eculizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab (NCT03056040, Study ALXN1210-PNH-302), ClinicalTrials.gov, 2026-11-13.
- A Study of Ravulizumab (ALXN1210) in Children and Adolescents With Paroxysmal Nocturnal Hemoglobinuria (NCT03406507, Study ALXN1210-PNH-304), ClinicalTrials.gov, 2026-11-13.
A reference drawn from the October 29, 2026 label, the drugmaker's published program and one public insurer policy shown as an example, checked on November 13, 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.