U.S. FDA APPROVED  DRUGS DURING 2018

Sr.No-  59

 ADVERSE REACTIONS

The most frequent adverse drug reactions (>10%) were upper respiratory infection and headache 

CONTRAINDICATIONS

ULTOMIRIS is contraindicated in patients with unresolved Neisseria Meningitidis infection

WARNINGS AND PRECAUTIONS

Use caution when administering ULTOMIRIS to patients with any other systemic infection

PATIENT COUNSELING INFORMATION

Advise the patient to read FDA-approved patient labeling (Medication Guide).

Meningococcal Infection                                                                                                Advise patients of the risk of meningococcal infection/sepsis. 

Inform patients that they are required to receive meningococcal vaccination at least 2 weeks prior to receiving the first dose of ULTOMIRIS, if they have not previously been vaccinated.

They are required to be revaccinated according to current medical guidelines for meningococcal vaccines use while on ULTOMIRIS therapy.

Inform patients that vaccination may not prevent meningococcal infection.

Inform patients about the signs and symptoms of meningococcal infection/sepsis, and strongly advise patients to seek immediate medical attention if these signs or symptoms occur.

These signs and symptoms are as follows:

• headache with nausea or vomiting                                                                                    • headache and a fever                                                                                                         • headache with a stiff neck or stiff back                                                                               • fever                                                                                                                                  • fever and a rash                                                                                                                   • confusion                                                                                                                           • muscle aches with flu-like symptoms

• eyes sensitive to light

Inform patients that they will be given an ULTOMIRIS Patient Safety Card that they should carry with them at all times.

This card describes symptoms which, if experienced, should prompt the patient to immediately seek medical evaluation.

Other Infections                                                                                                      Counsel patients of the increased risk of infections, particularly those due to encapsulated bacteria, especially Neisseria species. 

Advise patients of the need for vaccination against meningococcal infections according to current medical guidelines.

Counsel patients about gonorrhea prevention and advise regular testing for patients at risk.

Advise patients to report any new signs and symptoms of infection.

Discontinuation                                                                                                         Inform patients with PNH that they may develop hemolysis due to PNH when ULTOMIRIS is discontinued and that they will be monitored by their healthcare professional for at least 16 weeks following ULTOMIRIS discontinuation.

Inform patients who discontinue ULTOMIRIS to keep the ULTOMIRIS Patient Safety Card with them for eight months after the last ULTOMIRIS dose, because the increased risk of meningococcal infection persists for several weeks following discontinuation of ULTOMIRIS.

Infusion reactions                                                                                                     Advise patients that administration of ULTOMIRIS may result in infusion reactions. 

Manufactured by: Alexion Pharmaceuticals, Inc. 121 Seaport Boulevard Boston, MA 02210 USA US License Number 1743 This product, or its use, may be covered by one or more US patents, including US Patent No. 9,371,377; 9,079,949 and 9,663,574 in addition to others including

 CLINICAL PHARMACOLOGY

1. Mechanism of Action

Ravulizumab-cwvz is a terminal complement inhibitor that specifically binds to the complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a (the proinflammatory anaphylatoxin) and C5b (the initiating subunit of the terminal complement complex [C5b-9]) and preventing the generation of the terminal complement complex C5b9. ULTOMIRIS inhibits terminal complement-mediated intravascular hemolysis in patients with PNH. 

2. Pharmacodynamics

Immediate and complete inhibition of serum free C5 (concentration of less than 0.5 mcg/mL) was observed by the end of the first ULTOMIRIS infusion and sustained throughout the entire 26-week treatment period in all patients, both complement-inhibitor naïve and previously treated with eculizumab.

3. Pharmacokinetics

Ravulizumab-cwvz pharmacokinetics increase proportionally over a dose range of 200 to 5400 mg. 

Distribution                                                                                                                    The mean (SD) volume of distribution at steady state was 5.34 (0.92) L.

Elimination                                                                                                                     The mean (SD) terminal elimination half-life and clearance of ravulizumab-cwvz in patients with PNH are 49.7 (8.9) days and 0.08 (0.022) L/day respectively.

Specific Populations

No clinically significant differences in the pharmacokinetics of ravulizumab-cwvz were observed based on sex, age (18 to 83 years), race, hepatic impairment, or mild to moderate renal impairment (eGFR 30 to 89 mL/min/1.73 m2 , estimated by MDRD).

The effect of severe renal impairment (eGFR 15 to 29 mL/min/1.73 m2 , estimated by MDRD) on ravulizumab-cwvz pharmacokinetics is unknown.

Body weight was a significant covariate on the pharmacokinetics of ravulizumab-cwvz.

 USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary

There are no available data on ULTOMIRIS use in pregnant women to inform a drugassociated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

There are risks to the mother and fetus associated with untreated paroxysmal nocturnal hemoglobinuria (PNH) in pregnancy 

 The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

2. Lactation Risk summary

There are no data on the presence of ravulizumab-cwvz in human milk, the effect on the breastfed child, or the effect on milk production.

Since many medicinal products and immunoglobulins are secreted into human milk, and because of the potential for serious adverse reactions in a nursing child, breastfeeding should be discontinued during treatment and for 8 months after the final dose.

3. Pediatric Use

The safety and efficacy of ULTOMIRIS in pediatric patients have not been established.

4. Geriatric Use

Clinical studies of ULTOMIRIS did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.