Radicava

Other drugs may interact with edaravone, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Edaravone is a central nervous system agent.

Edaravone has the following uses:

Edaravone is indicated for the treatment of amyotrophic lateral sclerosis (ALS).1

General

Edaravone is available in the following dosage form(s) and strength(s):

• Injection: 30 mg/100 mL (0.3 mg/mL) in a single-dose polypropylene bag.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

The recommended dosage is 60 mg administered as an intravenous infusion over 60 minutes as follows:1

• Initial treatment cycle: daily dosing for 14 days, followed by a 14-day drug-free period.1

• Subsequent treatment cycles: daily dosing for 10 days out of 14-day periods, followed by 14-day drug-free periods.1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

In the U.S.

• Radicava

Available Dosage Forms:

• Solution

A doctor or other trained health professional will give you this medicine. It is given through a needle placed in a vein.

This medicine should come with a patient information leaflet. Read and follow the information carefully. Ask your doctor if you have any questions.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Mechanism of Action

The mechanism by which Radicava exerts its therapeutic effect in patients with ALS is unknown.

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.

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.

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.

Geriatric Patients

No age effect on edaravone pharmacokinetics has been found [see Use in Specific Populations (8.5)].

Patients with Renal and Hepatic Impairment

No pharmacokinetic data are available in patients with renal impairment or hepatic impairment [see Use in SpecificPopulations (8.6,8.7)].

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.

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.

How Supplied

Radicava injection is supplied as a 30 mg/100 mL (0.3 mg/mL) clear, colorless, sterile solution for intravenous infusion in single-dose polypropylene bags, each overwrapped with polyvinyl alcohol (PVA) secondary packaging containing an oxygen absorber and oxygen indicator, which should be pink to reflect appropriate oxygen levels [see Dosage and Administration (2.2) and How Supplied/Storage and Handling(16.2)]. These are supplied in cartons as listed below.

Storage and Handling

Store at up to 25°C (77°F). Excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from light. Store in overwrapped package to protect from oxygen degradation until time of use. The oxygen indicator will turn blue or purple if the oxygen has exceeded acceptable levels. Once the overwrap package is opened, use within 24 hours.

Radicava is injected into a vein through an IV. A healthcare provider will give you this injection.

Radicava is usually given in a 28-day treatment cycle. You may need to use the medicine only during the first 2 weeks of each cycle. Your doctor will determine how long to treat you with this medicine.

This medicine must be given slowly and the IV infusion can take at least 60 minutes to complete.

Usual Adult Dose for Amyotrophic Lateral Sclerosis:

-Initial Treatment Cycle: 60 mg once a day as IV infusion for 14 days followed by a 14-day drug-free period.

-Subsequent Treatment Cycles: 60 mg once a day as IV infusion for 10 days out of 14-day periods, followed by 14-day drug-free periods.

Comments:
-Administer each 60 mg dose as 2 consecutive 30 mg IV infusion bags over a total of 60 minutes (infusion rate approximately 1 mg per minute [3.33 mL per minute]).
-Upon the first observation of any signs or symptoms of a hypersensitivity reaction, promptly discontinue the infusion.

Use: Treatment of amyotrophic lateral sclerosis (ALS)

Other drugs may interact with edaravone, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.