A complement five (C5) inhibitor and produces rapid, complete, and sustained inhibition of C5 allowing for extended interval dosing as compared to eculizumab..
Inhibits the complement process by binding to the terminal complement C5.
It inhibits C5 from cleaving to C5a and C5b which is responsible for complement- mediated hemolysis associated with paroxysmal nocturnal hemoglobinuria.
Tradename Ultomoris.
Approved for the treatment of adults with paroxysmal nocturnal hemoglobinuria.
The FDA has approved the expanded use of ravulizumab-cwvz (Ultomiris) to include children aged 1 month and older, as well as adolescents, with paroxysmal nocturnal hemoglobinuria.
Ravulizumab-cwvz is a long-acting C5 inhibitor that is designed to provide complement inhibition.
The first and only FDA-approved treatment for this pediatric PNH population.
Non-inferior to eculizumab.
Administered IV as a loading dose, followed two weeks by a maintenance dose every eight weeks.
Patient must receive meningococcal vaccination, recommended at least two weeks prior to initiation of treatment.
Associated with headache, URI, dizziness, diarrhea, nausea, abdominal pain, limb pain, arthralgia, and fever.
REMS associated.
Ravulizumab-cwvz is approved for the treatment of adult and pediatric patients one month of age and older with atypical hemolytic uremic syndrome(atypical-HUS) to inhibit complement-mediated thrombotic microangiopathy (TMA).
Trade name Ultomiris.
Clinical symptoms of TMA include: changes in mental status, seizures, angina, dyspnea, thrombosis or increasing blood pressure.
In addition, a decrease in platelet count of 25% or more as compared to either baseline or to peak platelet count during drug treatment.
An increase in serum creatinine of 25% or more as compared to baseline or to nadir during drug treatment
an increase in serum LDH of 25% or more as compared to baseline or to nadir during ravulizumab treatment.
It is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).
Boxed WARNING for serious and life-threatening meningococcal infections/sepsis.
Atypical-HUS is an ultra-rare and life-threatening disorder caused by uncontrolled activation of the terminal complement pathway manifesting as thrombotic microangiopathy (TMA) characterized by thrombocytopenia, hemolysis, and renal impairment.
It is the first and only long-acting complement inhibitor that provides immediate, complete, and sustained C5 inhibition for 4-8 weeks in adult and pediatric patients one month of age and older weighing 5 kg or greater during the maintenance phase.
It provides about a 4x longer half-life, allowing adult and pediatric patients the freedom of every 4-8-week maintenance dosing, after the initial loading dose.
In studies, it met the primary end point, including normalization of hematological parameters and improvement in serum creatinine.
Adverse reactions reported in ≥20% of patients were upper respiratory tract infection, diarrhea, nausea, vomiting, headache, hypertension, and pyrexia.
Patients should be immunized with meningococcal vaccines at least 2 weeks prior to administering the first dose of ravulizumab unless the risks of delaying therapy outweigh the risk of developing a meningococcal infection.
Vaccination reduces, but does not eliminate, the risk of meningococcal infections.
Due to the serious risk of meningococcal infections, it is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS).
Meningococcal disease due to any serogroup may occur.
Its mean terminal elimination half-life of in patients with atypical-HUS is 51.8
days.
300 mg/30 mL vial
It is contraindicated in: Patients with unresolved Neisseria meningitidis infection, patients who are not currently vaccinated against Neisseria meningitidis.
It blocks terminal complement activation, with increased susceptibility to encapsulated bacteria infections, especially infections caused by Neisseria meningitis but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae.
Vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections should be administered according to ACIP guidelines.
Monitoring Disease Manifestations after treatment discontinuation for aHUS
treatment of aHUS should be a minimum duration of 6 months.
Due to heterogeneous nature of aHUS events and patient-specific risk factors, treatment duration beyond the initial 6 months should be individualized.
After discontinuing treatment, patients should be monitored for clinical symptoms and laboratory signs of TMA complications for at least 12 months.
If recurrence of findings, reinitiation of treatment or appropriate organ-specific supportive measures are employed.
Infusion reactions may occur and include: lower back pain, drop in blood pressure, infusion-related pain, elevation in blood pressure and limbs discomfort.
Most common adverse reactions in patients with aHUS treated: incidence of ≥20% upper respiratory tract infection, diarrhea, nausea, vomiting, headache, hypertension and pyrexia.
Serious adverse reactions were reported 57% patients with aHUS receiving the drug: hypertension, pneumonia and abdominal pain.