Ultomiris (Ravulizumab) is a monoclonal antibody that inhibits the terminal complement proteins by binding to the complement protein C5 (with high affinity) It inhibits  cleavage to C5a (the proinflammatory anaphylatoxin) and C5b (the initiating subunit of the terminal complement complex[C5b-9])

• It is used in the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in adults

Ultomiris dose in Adults

• Vaccinate with a meningococcal vaccine at least 2 weeks before treatment initiation
• revaccinate according to current guidelines.
• If urgent ravulizumab initiation is necessary and less than 2 weeks after vaccination, then give 2 weeks of antibacterial prophylaxis.
• In unvaccinated patients, give meningococcal vaccine as soon as possible and provide 2 weeks of antibacterial prophylaxis.
• Administer antimicrobial prophylaxis with oral antibiotics (penicillin, or macrolides if penicillin-allergic) during therapy to reduce the risk of meningococcal infection.
• Ravulizumab dosing schedule may be allowed to vary within 7 days of the scheduled infusion day.

Dosage in the treatment of Paroxysmal nocturnal hemoglobinuria:

The dose is based on weight at the time of treatment:

• ≥40 kg to <60 kg:

  • A loading dose of 2,400 mg is given
  • Maintenance dose of 3,000 mg is given once every 8 weeks starting 2 weeks after the loading dose

• ≥60 kg to <100 kg:

  • A loading dose of 2,700 mg is given
  • The maintenance dose is given as 3,300 mg once every 8 weeks starting 2 weeks after the loading dose

• ≥100 kg:

  • A loading dose of 3,000 mg
  • The maintenance dose is given as 3,600 mg once every 8 weeks starting 2 weeks after the loading dose

• Conversion from eculizumab:

  • When converting from eculizumab to ravulizumab, give ravulizumab loading dose 2 weeks after the last eculizumab dose
  • Then administer ravulizumab maintenance doses once every 8 weeks (beginning 2 weeks after the ravulizumab loading dose).

Ultomiris dose in Childrens

Not approved for use in children

Ultomiris (Ravulizumab) pregnancy Risk Category: C

• Untreated paroxysmal nocturnal hemoglobinuria (PNH), pregnant women and their fetuses experienced high rates of mortality and morbidity during pregnancy and postpartum.
• Negative maternal outcomes, such as worsening cytopenias and thrombotic events or bleeding, fetal death, and an increase in maternal mortality, are common.
• Also, there has been an increase in fetal deaths and preterm births.

Use Ravulizumab (Ultomiris), while breastfeeding

• It is unknown if ravulizumab can be found in breast milk.
• Breastfeeding is not recommended by the manufacturer because of the risk of serious adverse reactions in breastfed infants.
• This recommendation applies for therapy as well as for the first 8 months following the last dose.

Ultomiris dose in Kidney disease:

• Renal function can be estimated with the MDRD formula.

  • eGFR ≥30 mL/minute/1.73 m :

    • There are no dosage adjustments given in the manufacturer’s labeling
    • But eGFR 30 to 89 mL/minute/1.73 m had no clinically important effect on ravulizumab pharmacokinetics.

  • eGFR ≤29 mL/minute/1.73 m :

    • There are no dosage adjustments given in the manufacturer’s labeling

Ultomiris dose in Liver Disease:

• There are no dosage adjustments given in the manufacturer’s labeling

Common Side Effects of Ravulizumab (Ultomiris) Include:

• Central nervous system:

  • Headache

• Respiratory:

  • Upper respiratory tract infection

Less Common Side Effects of Ravulizumab (Ultomiris) Include:

• Central nervous system:

  • Dizziness

• Gastrointestinal:

  • Diarrhea
  • Nausea
  • Abdominal Pain

• Neuromuscular & Skeletal:

  • Limb Pain
  • Arthralgia

• Miscellaneous:

  • Fever

Contraindication to Ravulizumab (ultomiris) Include:

• Neisseria meningitidis unresolved infection

Warnings and precautions

• Infection

  • Ravulizumab is a drug that can prevent activation of the terminal complement
  • It can increase susceptibility to encapsulated bacteria infections, particularly Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus Influenzae.
  • If you administer ravulizumab ravulizumab, be sure to look out for signs and symptoms that could indicate a worsening infection.

• Infusion reactions

  • Infusion reactions may occur when ravulizumab is administered.
  • Ravulizumab discontinuation is not necessary for infusion reactions.
  • Withhold infusion if you notice signs of cardiac instability or respiratory compromise. You can also manage supportively.

• Meningococcal disease:

  • Ravulizumab has been shown to prevent life-threatening meningococcal infection/ sepsis.
  • Meningococcal infections can quickly become fatal if not treated promptly.
  • Follow the Advisory Committee on Immunization Practices' (ACIP) recommendations for meningococcal vaccines in patients with complement deficiency.
  • If you are concerned about developing a meningococcal disease, it is important to immunize your body with meningococcal vaccinations at least 14 days before administering the first dose of ravulizumab.
  • Vaccination can reduce, but not eliminate, the chance of developing meningococcal infection.
  • Assess for signs and symptoms of meningococcal infection early on. If an infection is suspected, immediately treat it.
  • Ravulizumab can increase the susceptibility to meningococcal infection (septicemia) and/or meningitis.
  • Any serogroup can cause meningococcal diseases.
  • In the event of an emergency, give meningococcal vaccine(s), and at least two weeks of antibacterial prophylaxis to any unvaccinated patients.
  • Consider antimicrobial prophylaxis using oral antibiotics (penicillin or macrolides, if penicillin-allergic), for the duration of ravulizumab treatment to reduce the chance of meningococcal diseases.
  • Inform patients about the signs and symptoms of meningitis. Also, explain to them how to get immediate medical attention.
  • Patients undergoing treatment for severe meningococcal disease should be advised to stop taking ravulizumab.
  • ACIP recommends revaccinate to treat meningococcal diseases.

Monitor:

• Before starting treatment, make sure you have checked your immunization status.
• Examine for signs and symptoms of meningococcal disease early on
• If you suspect an infection, get treatment immediately.
• If you administer ravulizumab (to patients with systemic active infections), be sure to look out for any signs or symptoms that could indicate a worsening infection.
• Watch out for infusion reactions.

Discontinuation of ravulizumab, (Ultomiris).:

• To detect hemolysis or other reactions, it is important to monitor your body for at least four months after discontinuation.
• After stopping ravulizumab treatment, look out for signs/symptoms such as fatigue, hemoglobinuria and abdominal pain.

How to administer Ravulizumab (Ultomiris)?

• Administer through a 0.22-micron filter intravenously.
• Allow the solution to adjust to room temperature at ambient air temperature (do not use a heat source) before infusion.
• The infusion rate is based on the patient's weight.

≥40 kg to <60 kg:

• Give loading dose (2,400 mg in a total volume of 480 mL) @ 252 ml/hour.
• Give maintenance dose (3,000 mg in a total volume of 600 mL) @ 257 mL/hour.

≥60 kg to <100 kg:

• Administer loading dose (2,700 mg in a total volume of 540 mL) at 317 mL/hour.
• Infuse maintenance dose (3,300 mg in a total volume of 660 mL) @ 330 mL/hour.

100 kg or more:

• Infuse loading dose (3,000 mg in a total volume of 600 mL) @ 333 mL/hour.
• Give maintenance dose (3,600 mg in a total volume of 720 mL) at 327 mL/hour.

Mechanism of action of Ravulizumab (Ultomiris):

• 0.08 L/day
• Ravulizumab, a monoclonal humanized antibody that binds primarily to C5 (high affinity), is a terminal complement inhibitor.
• It prevents the cleavage of C5a (the anaphylactic proinflammatory drug) and C5b (2,0 subunit of terminal complement complex[C5b-9]).
• It stops the generation of C5b9 terminal complement complex.
• Ravulizumab's C5 inhibition against complement-mediated hemolysis in patients with paroxysmal or nocturnal hemoglobinuria results in an immediate, sustained, and thorough treatment.

Onset:

LDH reduction:

• It is rapid and sustained, beginning as early as day 8 .
• LDH normalization:
• By week 4 (in complement-inhibitor naive patients).

Distribution: V :

• 5.34 L

Half-life elimination: Terminal:

• 49.7 days

Excretion: Clearance:

International brands of Ultomiris:

• Ultomiris

Ultomiris Brands in Pakistan:

Ravulizumab ( Ultomiris ) is not available in Pakistan. [/bg_collapse]