Ultomiris (Ravulizumab)
Monoclonal antibody – Complement C5 inhibitor for PNH, aHUS, gMG & NMOSD
Quick Facts About Ultomiris
Key Takeaways About Ultomiris
- Complement C5 inhibitor: Ultomiris blocks the complement protein C5 to prevent immune-mediated cell destruction in PNH, aHUS, gMG, and NMOSD
- Meningococcal vaccination required: All patients must be vaccinated against meningococcal infection at least 2 weeks before starting treatment due to increased risk of serious infections
- Less frequent dosing than Soliris: Maintenance infusions every 8 weeks (vs. every 2 weeks with eculizumab), reducing treatment burden
- Weight-based dosing: Both loading and maintenance doses are calculated based on body weight, given as an intravenous infusion
- Do not stop abruptly: Discontinuing treatment can cause severe rebound symptoms including hemolysis, thrombosis, and organ damage – always consult your doctor
What Is Ultomiris and What Is It Used For?
Ultomiris (ravulizumab) is a monoclonal antibody that targets complement protein C5, a key component of the body's complement immune system. By blocking C5, Ultomiris prevents the formation of the membrane attack complex, thereby protecting cells from complement-mediated destruction. It is administered as an intravenous infusion and is approved for several rare, serious conditions.
Ultomiris belongs to a class of medications known as monoclonal antibodies. It was specifically engineered to bind to complement protein C5, which is a critical component of the innate immune system known as the complement cascade. Under normal circumstances, the complement system plays an essential role in defending the body against infections and clearing damaged cells. However, in certain diseases, the complement system becomes overactive or misdirected, leading to the destruction of the body's own healthy cells and tissues.
By binding to C5, ravulizumab prevents the protein from being cleaved into its active fragments – C5a (a potent inflammatory mediator) and C5b (which initiates the formation of the terminal complement complex C5b-9, also known as the membrane attack complex or MAC). This inhibition is the cornerstone of Ultomiris's therapeutic effect across all of its approved indications.
Paroxysmal Nocturnal Hemoglobinuria (PNH)
PNH is a rare, acquired, life-threatening blood disorder in which the complement system attacks and destroys red blood cells (a process called hemolysis). This leads to anemia, fatigue, dark urine (especially in the morning), difficulty swallowing, erectile dysfunction, abdominal pain, shortness of breath, and an increased risk of blood clots (thrombosis). Ultomiris is approved for adults and children weighing 10 kg or more with PNH, including patients who are new to complement inhibitor therapy and those who have been treated with eculizumab (Soliris) for at least the previous 6 months.
Atypical Hemolytic Uremic Syndrome (aHUS)
aHUS is a rare, serious condition in which uncontrolled complement activation damages small blood vessels, particularly in the kidneys. This leads to low platelet counts (thrombocytopenia), destruction of red blood cells (hemolytic anemia), and kidney failure. Without treatment, aHUS can be rapidly progressive and may lead to end-stage renal disease or death. Ultomiris is approved for patients weighing 10 kg or more with aHUS, both as initial therapy and for patients who have been on eculizumab for at least 3 months.
Generalized Myasthenia Gravis (gMG)
Generalized myasthenia gravis is an autoimmune neuromuscular disorder in which the immune system produces antibodies that attack the neuromuscular junction – the point where nerves communicate with muscles. This leads to debilitating muscle weakness affecting the eyes (ptosis, double vision), limbs, breathing muscles, and muscles involved in swallowing and speech. Ultomiris is approved for adult patients with gMG who remain symptomatic despite treatment with other immunosuppressive therapies. It specifically targets the complement-mediated component of the disease.
Neuromyelitis Optica Spectrum Disorder (NMOSD)
NMOSD is a rare autoimmune condition primarily affecting the optic nerves and spinal cord. The immune system, driven in part by complement activation, attacks and damages these structures, causing episodes (relapses) of vision loss, limb weakness or paralysis, painful spasms, loss of sensation, and bladder and bowel dysfunction. Ultomiris is approved for adult patients with NMOSD to reduce the risk of relapses, particularly in patients who are anti-aquaporin-4 (AQP4) antibody positive.
Ultomiris is the successor to eculizumab (Soliris), also made by Alexion. The key advantage of Ultomiris is its longer half-life, which allows maintenance dosing every 8 weeks instead of every 2 weeks. Clinical trials have shown that Ultomiris is non-inferior to eculizumab in efficacy while offering improved patient convenience.
What Should You Know Before Taking Ultomiris?
Before starting Ultomiris, you must be vaccinated against meningococcal infection. Do not use Ultomiris if you are allergic to ravulizumab, if you have not been vaccinated against meningococcal disease, or if you have an active meningococcal infection. Tell your doctor about all other medications, infections, and whether you are pregnant or breastfeeding.
Contraindications
Ultomiris must not be used in the following situations:
- Allergy to ravulizumab or any other ingredient in Ultomiris (including polysorbate 80, arginine, sucrose, sodium phosphate)
- Unvaccinated against meningococcal infection – vaccination is mandatory before starting treatment
- Active meningococcal infection – treatment must not be initiated during active infection
Warnings and Precautions
The most critical warning associated with Ultomiris relates to the increased risk of serious meningococcal infections. Because the drug blocks complement protein C5, which is essential for fighting certain bacterial infections, patients are significantly more vulnerable to infections caused by Neisseria meningitidis. These infections can progress rapidly to meningitis (infection of the brain membranes), encephalitis (brain inflammation), and sepsis (blood poisoning), all of which can be fatal if not treated promptly.
All patients must receive meningococcal vaccination at least 2 weeks before starting Ultomiris. If vaccination cannot be given 2 weeks in advance, your doctor will prescribe prophylactic antibiotics until 2 weeks after vaccination. Even with vaccination, meningococcal infection can still occur. Seek immediate medical attention if you experience: severe headache with nausea or vomiting, headache with stiff neck or back, fever with or without rash, confusion, muscle aches with flu-like symptoms, or sensitivity to light.
All patients receive a patient safety card listing the signs and symptoms of meningococcal infection. You should carry this card at all times and show it to any healthcare professional who treats you. If you are traveling to areas with limited medical access, your doctor may prescribe standby antibiotics for emergency use.
Patients under 18 years of age must also be vaccinated against Haemophilus influenzae type b and pneumococcal infections, as complement inhibition increases susceptibility to encapsulated bacteria in general.
Infusion-Related Reactions
As with all intravenous biological therapies, infusion-related reactions can occur during or shortly after administration of Ultomiris. These may include headache, lower back pain, nausea, and pain at the infusion site. In rare cases, severe allergic reactions (anaphylaxis) can occur, causing breathing difficulties, dizziness, and a drop in blood pressure. For this reason, patients are typically monitored for at least one hour after each infusion, and healthcare professionals should have appropriate resuscitation equipment available.
Pregnancy and Breastfeeding
The effects of Ultomiris on the developing fetus have not been fully established in humans. As an IgG1 monoclonal antibody, ravulizumab is expected to cross the placental barrier, particularly during the second and third trimesters. Animal studies have not shown direct teratogenic effects, but complement inhibition during pregnancy could theoretically affect the immune system of the developing baby.
Women of childbearing potential should use effective contraception during treatment and for at least 8 months after the last dose. Ultomiris is not recommended during pregnancy unless the potential benefit justifies the potential risk to the fetus. It is unknown whether ravulizumab is excreted in human breast milk, so a decision should be made whether to discontinue breastfeeding or to discontinue treatment, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother.
Driving and Operating Machinery
Ultomiris has no or negligible effect on the ability to drive or operate machinery.
Important Information About Ingredients
Ultomiris contains sodium and polysorbat 80. After dilution with sodium chloride 9 mg/ml (0.9%), the solution contains up to 0.18 g sodium per maximum dose, equivalent to approximately 9% of the WHO recommended maximum daily sodium intake for adults. This should be taken into consideration by patients on a sodium-restricted diet. Polysorbate 80 may cause allergic reactions in susceptible individuals – inform your doctor if you have any known allergies.
How Does Ultomiris Interact with Other Drugs?
No formal drug interaction studies have been conducted with Ultomiris. As a monoclonal antibody, ravulizumab is not metabolized by cytochrome P450 enzymes and is not expected to have direct pharmacokinetic interactions with most conventional drugs. However, certain immunosuppressive therapies and other complement-modifying treatments may affect or be affected by concurrent use.
Because Ultomiris is a large protein molecule (monoclonal antibody), it is catabolized through general protein degradation pathways rather than through hepatic cytochrome P450 enzymes. This means that conventional drug-drug interactions affecting liver metabolism are unlikely. However, clinicians should still consider the following when prescribing Ultomiris alongside other medications:
| Drug / Class | Type | Clinical Significance |
|---|---|---|
| Eculizumab (Soliris) | Complement C5 inhibitor | Do not co-administer; when switching from eculizumab, start Ultomiris 2 weeks after last eculizumab dose |
| Rituximab, azathioprine, mycophenolate | Immunosuppressants | Often used concurrently in gMG/NMOSD; monitor for increased infection risk due to cumulative immunosuppression |
| Meningococcal vaccines | Vaccination | Must be given at least 2 weeks before starting Ultomiris; concurrent immunosuppressants may reduce vaccine efficacy |
| Plasma exchange / plasmapheresis | Procedure | Can remove ravulizumab from the blood; a supplemental dose of Ultomiris may be required after plasma exchange |
| IVIg (intravenous immunoglobulin) | Immunomodulatory | May affect ravulizumab clearance through the neonatal Fc receptor (FcRn); monitor treatment response |
Always inform your doctor, pharmacist, or nurse about all medicines you are currently taking, have recently taken, or might take. This includes prescription drugs, over-the-counter medications, herbal supplements, and vitamins. While direct pharmacokinetic interactions are unlikely, the cumulative effect of multiple immunosuppressive agents should always be considered.
What Is the Correct Dosage of Ultomiris?
Ultomiris dosing is based on body weight. Treatment begins with a loading dose, followed by maintenance doses every 8 weeks (for patients ≥20 kg) or every 4 weeks (for patients 10–20 kg). The drug is given as an intravenous infusion lasting approximately 25 to 75 minutes depending on the dose.
Your doctor will calculate the appropriate dose of Ultomiris based on your body weight at the time of treatment. The dosing regimen consists of two phases: an initial loading dose to rapidly achieve therapeutic drug levels, and regular maintenance doses to maintain complement C5 inhibition over time.
Adults and Children (Weight-Based Dosing)
| Body Weight | Loading Dose | Maintenance Dose | Maintenance Interval |
|---|---|---|---|
| 10 to <20 kg* | 600 mg | 600 mg | Every 4 weeks |
| 20 to <30 kg* | 900 mg | 2,100 mg | Every 8 weeks |
| 30 to <40 kg* | 1,200 mg | 2,700 mg | Every 8 weeks |
| 40 to <60 kg | 2,400 mg | 3,000 mg | Every 8 weeks |
| 60 to <100 kg | 2,700 mg | 3,300 mg | Every 8 weeks |
| ≥100 kg | 3,000 mg | 3,600 mg | Every 8 weeks |
* Weight categories 10–<20 kg, 20–<30 kg, and 30–<40 kg apply only to PNH and aHUS indications.
The first maintenance dose is given 2 weeks after the loading dose. If you were previously treated with eculizumab (Soliris), the loading dose of Ultomiris should be given 2 weeks after your last eculizumab infusion to ensure continuous complement inhibition.
How Ultomiris Is Administered
Ultomiris is always given as an intravenous infusion (a drip into a vein) by a healthcare professional in a hospital or clinical setting. The concentrate must be diluted with sodium chloride 0.9% before infusion and administered through a 0.2-micrometre filter. The infusion duration varies depending on the dose and body weight, ranging from approximately 25 minutes for the smallest doses to approximately 75 minutes for larger maintenance doses. Patients are observed for at least one hour after the infusion for signs of infusion-related reactions.
Elderly Patients
No specific dose adjustment is required for elderly patients aged 65 years and older. However, clinical experience with Ultomiris in elderly patients with PNH, aHUS, and NMOSD is limited. Elderly patients should be treated with the same weight-based dosing regimen as younger adults, with close monitoring for adverse effects given that older patients may have greater susceptibility to infections.
Missed Dose
If you miss a scheduled infusion, contact your doctor immediately. It is crucial to maintain regular dosing to ensure continuous complement C5 inhibition. A gap in treatment could allow complement activity to resume, leading to a flare of your underlying condition. Your doctor will advise you on the best course of action, which may include scheduling the missed dose as soon as possible and adjusting subsequent dosing intervals.
Overdose
No cases of overdose with Ultomiris have been reported in clinical trials. Due to its mechanism of action, excessive complement inhibition would theoretically increase the risk of infections, particularly meningococcal disease. If an overdose is suspected, the patient should be monitored closely and treated symptomatically. There is no specific antidote for ravulizumab.
What Are the Side Effects of Ultomiris?
Like all medicines, Ultomiris can cause side effects, although not everybody gets them. The most serious potential side effect is meningococcal infection. Common side effects include headache, upper respiratory tract infections, diarrhea, nausea, fatigue, and joint pain.
Your doctor will discuss the potential side effects with you before starting treatment and explain the balance of benefits and risks. The side effects listed below are based on clinical trial data from the pivotal studies of Ultomiris across its approved indications. Side effects are organized by frequency, from most common to rarest.
The most serious adverse reaction is meningococcal infection, including meningococcal sepsis and meningococcal encephalitis. If you experience any symptoms of meningococcal infection (severe headache, stiff neck, fever, rash, confusion, sensitivity to light), seek emergency medical attention immediately. See Warnings and Precautions for more details.
Very Common
- Headache
- Dizziness
- Diarrhea, nausea, abdominal pain
- Fever (pyrexia), fatigue
- Upper respiratory tract infection
- Common cold (nasopharyngitis)
- Back pain, joint pain (arthralgia)
- Urinary tract infection
Common
- Vomiting, indigestion (dyspepsia)
- Hives (urticaria), skin rash, itching (pruritus)
- Muscle pain (myalgia) and muscle cramps
- Flu-like illness, chills, weakness (asthenia)
- Infusion-related reaction
- Allergic reaction (hypersensitivity)
Uncommon
- Meningococcal infection
- Severe allergic reaction (anaphylactic reaction) causing breathing difficulties or dizziness
- Disseminated gonococcal infection
Most side effects of Ultomiris are mild to moderate and tend to improve over time as the body adjusts to the medication. Infusion-related reactions are most common during the first few infusions and typically become less frequent with subsequent treatments. If you experience any side effects that are bothersome, persistent, or concerning, report them to your healthcare provider.
It is important to note that infections in general may be more common in patients taking Ultomiris, because the complement system is part of the body's defense against bacteria. Beyond meningococcal disease, patients should be aware of an increased susceptibility to other infections caused by encapsulated bacteria, including gonorrheal infections. Maintaining up-to-date vaccinations and practicing good hygiene can help reduce this risk.
How Should You Store Ultomiris?
Ultomiris must be stored in a refrigerator at 2°C–8°C (36°F–46°F). Do not freeze. Keep the vials in the original packaging to protect from light. Once diluted, the solution should be used immediately or within 24 hours if refrigerated.
As Ultomiris is typically administered in a hospital or clinical setting, storage is generally managed by healthcare professionals. However, patients should be aware of the following storage conditions:
- Refrigeration: Store unopened vials in a refrigerator at 2°C to 8°C (36°F to 46°F)
- Do not freeze: Freezing can damage the protein structure of the monoclonal antibody, rendering it ineffective
- Light protection: Keep vials in the original carton to protect from light
- After dilution: The diluted solution should be used immediately. If not used immediately, it may be stored for up to 24 hours at 2°C–8°C or up to 4 hours at room temperature
- Expiry date: Do not use after the expiry date stated on the carton (the last day of the stated month)
- Appearance: Ultomiris is a clear to slightly yellowish solution. Do not use if it appears cloudy, contains visible particles, or is discolored
Keep all medicines out of the sight and reach of children. Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help protect the environment.
What Does Ultomiris Contain?
Each 3 ml vial of Ultomiris contains 300 mg of ravulizumab as the active ingredient. The inactive ingredients include disodium hydrogen phosphate heptahydrate, sodium dihydrogen phosphate monohydrate, polysorbate 80, arginine, sucrose, and water for injections.
Understanding the composition of Ultomiris is important for identifying potential allergens and ensuring safe administration. The formulation is designed to maintain the stability and biological activity of the ravulizumab monoclonal antibody.
Active Ingredient
The active substance is ravulizumab, a humanized monoclonal antibody of the IgG1/IgG4 subclass. Each vial contains 300 mg of ravulizumab in 3 ml of concentrate, yielding a concentration of 100 mg/ml before dilution. After dilution with sodium chloride 0.9%, the final infusion concentration is 50 mg/ml.
Inactive Ingredients (Excipients)
- Disodium hydrogen phosphate heptahydrate (E 339) – buffer to maintain pH stability
- Sodium dihydrogen phosphate monohydrate (E 339) – buffer component
- Polysorbate 80 (E 433) – surfactant to prevent protein aggregation (may cause allergic reactions in susceptible individuals)
- Arginine – amino acid stabilizer
- Sucrose – lyoprotectant/stabilizer
- Water for injections – solvent
Ultomiris is manufactured by Alexion Pharma International Operations Limited in Dublin, Ireland, and distributed by Alexion Europe SAS. The marketing authorization holder is Alexion Europe SAS, based in Levallois-Perret, France.
What Happens If You Stop Taking Ultomiris?
Stopping Ultomiris can cause a serious return of disease symptoms. In PNH, this may include severe hemolysis, blood clots, and organ damage. In aHUS, it may cause kidney failure. Never stop treatment without consulting your doctor, who will monitor you closely for at least 16 weeks after discontinuation.
Stopping Treatment for PNH
If you discontinue Ultomiris for PNH, complement-mediated hemolysis can resume and may be more severe than before treatment (rebound hemolysis). This can result in a significant drop in red blood cell count, causing severe anemia, dark urine, fatigue, abdominal pain, shortness of breath, difficulty swallowing, chest pain, kidney problems (elevated serum creatinine), and an increased risk of blood clots. Your doctor will monitor you closely for at least 16 weeks after your last dose.
Stopping Treatment for aHUS
Discontinuation of Ultomiris in aHUS may lead to a recurrence of thrombotic microangiopathy (TMA), which can cause a significant decrease in platelet count, increased red blood cell destruction, reduced urine output, elevated creatinine levels (kidney damage), and blood clots. Other symptoms may include confusion, visual changes, chest pain, and abdominal pain with diarrhea. Close medical monitoring is essential after stopping treatment.
Stopping Treatment for gMG and NMOSD
If you stop Ultomiris for gMG or NMOSD, your symptoms may return, including muscle weakness, breathing difficulties, vision problems, pain, and impaired daily functioning. Always discuss discontinuation with your doctor, who will recommend an appropriate tapering strategy and ongoing monitoring. Abrupt cessation without alternative immunosuppressive therapy may lead to a disease flare or crisis.
Frequently Asked Questions About Ultomiris
Both Ultomiris (ravulizumab) and Soliris (eculizumab) are complement C5 inhibitors manufactured by Alexion. The key difference is that Ultomiris has been engineered to have a significantly longer half-life. This means that Ultomiris requires maintenance infusions only every 8 weeks, compared to every 2 weeks for Soliris. Clinical trials have demonstrated that Ultomiris is non-inferior to eculizumab across all approved indications, meaning it is at least as effective. The reduced frequency of infusions significantly improves patient convenience and quality of life.
Ultomiris works by blocking complement protein C5, which is a critical part of the immune system's defense against certain bacteria, particularly Neisseria meningitidis (meningococcus). Without a functioning C5, your body cannot form the membrane attack complex needed to kill these bacteria. Meningococcal infections can cause meningitis, sepsis, and death if untreated. Vaccination significantly reduces but does not eliminate this risk. You must be vaccinated at least 2 weeks before starting treatment, and you should keep your vaccination up to date throughout treatment.
Yes, you can and should receive appropriate vaccines while on Ultomiris. In fact, keeping vaccinations current is especially important because Ultomiris suppresses part of your immune system. However, if you are also taking other immunosuppressive medications (such as rituximab, azathioprine, or mycophenolate), the effectiveness of vaccines may be reduced. Discuss your vaccination schedule with your doctor to ensure optimal protection. Live vaccines should generally be used with caution in immunocompromised patients.
The infusion time depends on the dose, which is based on your body weight. Loading dose infusions typically take between 25 and 45 minutes, while maintenance dose infusions range from 30 to 75 minutes. After the infusion is complete, you will usually be observed for approximately one hour for any signs of infusion-related reactions. In total, you should expect to spend approximately 1.5 to 2.5 hours at the infusion center for each visit.
Ultomiris is approved for children weighing 10 kg or more for the treatment of PNH and aHUS. The dosing is weight-based, with specific dose levels for pediatric weight categories. Children under 18 must receive additional vaccinations against Haemophilus influenzae type b and pneumococcal infections before starting treatment. For gMG and NMOSD, Ultomiris is currently approved only for adult patients, as clinical trial data in pediatric populations for these indications is not yet available.
If you miss a scheduled Ultomiris infusion, contact your doctor or treatment center immediately. It is important not to let a significant gap occur between doses, as this could allow complement activity to return and your disease to flare. Your doctor will arrange for the missed infusion to be given as soon as possible and may adjust the timing of your subsequent doses accordingly. Do not try to make up for a missed dose by doubling the next one.
References
- European Medicines Agency (EMA). Ultomiris (ravulizumab) – Summary of Product Characteristics. Last updated 2025. Available at: EMA EPAR Ultomiris.
- U.S. Food and Drug Administration (FDA). Ultomiris Prescribing Information. Alexion Pharmaceuticals, Inc. Revised 2025.
- Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, et al. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood. 2019;133(6):530-539. doi:10.1182/blood-2018-09-876136.
- Kulasekararaj AG, Hill A, Rottinghaus ST, et al. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor–experienced adult patients with PNH: the 302 study. Blood. 2019;133(6):540-549. doi:10.1182/blood-2018-09-876805.
- Rondeau E, Scully M, Ariceta G, et al. The long-acting C5 inhibitor, ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment. Kidney Int. 2020;97(6):1287-1296. doi:10.1016/j.kint.2020.01.035.
- Vu T, Meisel A, Bhatt M, et al. Ravulizumab in generalized myasthenia gravis: a phase 3, randomized, double-blind, placebo-controlled study (CHAMPION MG). Lancet Neurol. 2022;21(7):595-606. doi:10.1016/S1474-4422(22)00185-5.
- Pittock SJ, Barnett M, Bennett JL, et al. Ravulizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder (CHAMPION-NMOSD). N Engl J Med. 2023;389(26):2395-2408. doi:10.1056/NEJMoa2311156.
- World Health Organization (WHO). Model List of Essential Medicines – 23rd list, 2023. Geneva: WHO; 2023.
- Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014;124(18):2804-2811. doi:10.1182/blood-2014-02-522128.
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Medical Editorial Team
This article has been written, fact-checked, and medically reviewed by the iMedic Medical Editorial Team. Our team consists of licensed physicians, pharmacologists, and medical researchers with expertise in hematology, neurology, immunology, and clinical pharmacology.
iMedic Medical Editorial Team
Specialists in Hematology, Clinical Pharmacology & Rare Diseases
GRADE Evidence Level 1A
Based on phase 3 RCTs, systematic reviews & EMA/FDA regulatory data
EMA, FDA, WHO
Independent, no pharmaceutical funding
Next review scheduled within 12 months