Edaravone - Radicava-@- (May 2017) - Neurological disorders
Drug Name:Edaravone - Radicava-@- (May 2017) - Neurological disorders
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
Drug Interaction Studies
The pharmacokinetics of edaravone is not expected to be significantly affected
by inhibitors of CYP enzymes,UGTs, or major transporters.
In vitro studies demonstrated that, at clinical dose, edaravone and its metabolites
are not expected to significantly inhibit cytochrome P450 enzymes (CYP1A2,
CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6,CYP3A4), UGT1A1, UGT2B7,
or transporters (P-gp, BCRP, OATP1B1, OATP1B3, OAT1, OAT3, and
OCT2) in humans.
Edaravone and its metabolites are not expected to induce CYP1A2, CYP2B6,
or CYP3A4 at the clinical dose level of RADICAVA.
Indication:
U.S. FDA APPROVED DRUGS DURING 2017
Sr.No- 20
Name of the Drug- Radicava
Active Ingredient- Edaravone Pharmacological Classification-
To treat patients with amyotrophic sclerosis(ALS)
Date of Approval- 05-05-2017
(Ref- FDA approved List 2017)
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
RADICAVA safely and effectively.
See full prescribing information for RADICAVA.
RADICAVA (edaravone injection), for intravenous use
Initial U.S. Approval: 2017 INDICATIONS AND USAGE
RADICAVA is indicated for the treatment of amyotrophic lateral sclerosis
(ALS)
Adverse Reaction:
ADVERSE REACTIONS
Most common adverse reactions (at least 10% and greater than placebo) are
contusion, gait disturbance, and headache.
Contra-Indications:
CONTRAINDICATIONS
Patients with a history of hypersensitivity to edaravone or any of the inactive
ingredients in RADICAVA
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions:
Advise patients to seek immediate medical care
Sulfite Allergic Reactions:
RADICAVA contains sodium bisulfite,which may cause allergic type reactions
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
RADICAVA is indicated for the treatment of amyotrophic lateral sclerosis
(ALS)
DOSAGE AND ADMINISTRATION
The recommended dosage is 60 mg administered as an intravenous infusion
over 60 minutes as follows:
Initial treatment cycle: daily dosing for 14 days followed by a 14-
day drug-free period
Subsequent treatment cycles: daily dosing for 10 days out of 14-
day periods, followed by 14-day drug-free periods.
DOSAGE FORMS AND STRENGTHS
Injection: 30 mg/100 mL in a single-dose polypropylene bag
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patients to read the FDA-approved patient labeling (Patient Information).
Hypersensitivity Reactions
Advise patients to seek immediate medical care if they experience signs or
symptoms of a hypersensitivity reaction.
Sulfite Allergic Reactions
Advise patients about potential for sulfite sensitivity.
Inform patients that RADICAVA contains sodium bisulfite, which may cause
allergic type reactions including anaphylactic symptoms and life-threatening or less
severe asthmatic episodes, and to seek immediate medical care if they
experience these signs or symptoms.
Pregnancy and Breastfeeding
Advise patients to notify their healthcare provider if they become pregnant or
intend to become pregnant during RADICAVA therapy
Advise patients to notify their healthcare provider if they intend breastfeed
or are breastfeeding an infant.
Marketed and distributed by:
MT Pharma America, Inc., a US subsidiary of Mitsubishi Tanabe Pharma Corporation
525 Washington Blvd., Suite 400,
Jersey City, NJ 07310
RADICAVA is a trademark of Mitsubishi Tanabe Pharma Corporation
© Mitsubishi Tanabe Pharma Corporation [2017]
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1.Mechanism of Action
The mechanism by which RADICAVA exerts its therapeutic effect in patients with ALS
is unknown.
2. Pharmacokinetics
RADICAVA is administered by IV infusion. The maximum plasma concentration
(Cmax) of edaravone was reached by the end of infusion. There was a trend of
more than dose-proportional increase in area under the concentration-time curve
(AUC) and Cmax of edaravone. With multiple-dose administration, edaravone does
not accumulate in plasma.
Distribution
Edaravone is bound to human serum proteins (92%), mainly to albumin, with no
concentration dependence in the range of 0.1 to 50 micromol/L.
Elimination
The mean terminal elimination half-life of edaravone is 4.5 to 6 hours. The half-lives
of its metabolites are 2 to 2.8 hours.
Metabolism
Edaravone is metabolized to a sulfate conjugate and a glucuronide conjugate,
which are not pharmacologically active. The glucuronide conjugation of
edaravone involves multiple uridine diphosphate glucuronosyltransferase
(UGT) isoforms (UGT1A6, UGT1A9, UGT2B7, and UGT2B17) in the liver and
kidney.
In human plasma, edaravone is mainly detected as the sulfate conjugate,
which is presumed to be formed by sulfotransferases.
Excretion
In Japanese and Caucasian healthy volunteer studies, edaravone was excreted
mainly in the urine as its glucuronide conjugate form (70-90% of the dose).
Approximately 5-10% of the dose was recovered in the urine as sulfate conjugate,
and only 1% of the dose or less was recovered in the urine as unchanged form.
In vitro studies suggest that sulfate conjugate of edaravone is hydrolyzed back
to edaravone, which is then converted to the glucuronide conjugate in the human
kidney before excretion into the urine.
Specific Populations
Geriatric Patients
No age effect on edaravone pharmacokinetics has been found.
Patients with Renal and Hepatic Impairment
No pharmacokinetic data are available in patients with renal impairment or
hepatic impairment.
Male and Female Patients
No gender effect on edaravone pharmacokinetics has been found.
Racial or Ethnic Groups
There were no significant racial differences in Cmax and AUC of edaravone
between Japanese and Caucasian subjects.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
There are no adequate data on the developmental risk associated with the use
of RADICAVA in pregnant women
In animal studies, administration of edaravone to pregnant rats and rabbits
resulted in adverse developmental effects (increased mortality, decreased
growth, delayed sexual development, and altered behavior) at clinically
relevant doses.
Most of these effects occurred at doses that were also associated with
maternal toxicity.
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. The background risk for major birth defects and
miscarriage in patients with ALS is unknown.
2. Lactation
Risk Summary
There are no data on the presence of edaravone in human milk, the effects
on the breastfed infant, or the effects of the drug on milk production.
Edaravone and its metabolites are excreted in the milk of lactating rats.
The developmental and health benefits of breastfeeding should be considered
along with the mother’s clinical need for RADICAVA and any potential adverse
effects on the breastfed infant from RADICAVA or from the underlying maternal
condition.
3. Pediatric Use
Safety and effectiveness of RADICAVA in pediatric patients have not been established.
4. Geriatric Use
Of the 184 patients with ALS who received RADICAVA in 3 placebo-controlled
clinical trials, a total of 53 patients were 65 years of age and older, including
2 patients 75 years of age and older.
No overall differences in safety or effectiveness were observed between these
patients and younger patients, but greater sensitivity of some older individuals
cannot be ruled out.
5.Renal Impairment
The effect of renal impairment on the pharmacokinetics of RADICAVA has no
been studied. However, renal impairment is not expected to significantly affect
the exposure to edaravone. No dose adjustment is needed in these patients.
6. Hepatic Impairment
The effect of hepatic impairment on the pharmacokinetics of RADICAVA has not
been studied. No dose adjustment is needed for patients with mild or moderate
hepatic impairment. No specific dosing recommendation can be provided
for patients with severe hepatic impairment.
