Usage
Edaravone is prescribed for the treatment of Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease. It is classified as a neuroprotective agent, specifically a free radical scavenger. Edaravone is thought to work by protecting nerve cells in the brain and spinal cord from damage caused by oxidative stress.
Alternate Names
- International Nonproprietary Name (INN): Edaravone
- Brand names: Radicava, Radicava ORS
How It Works
Pharmacodynamics: Edaravone acts as a free radical scavenger, reducing oxidative stress, which is believed to contribute to the neuronal damage seen in ALS. Although the exact mechanism in ALS is unknown, it may also exert neuroprotective effects through other pathways, including anti-inflammatory and anti-apoptotic effects.
Pharmacokinetics:
- Absorption: Edaravone administered intravenously reaches peak plasma concentration at the end of the infusion. Oral edaravone has reduced bioavailability compared to IV but reaches peak concentrations in 1-2 hours.
- Distribution: Edaravone is widely distributed throughout the body and is highly protein-bound.
- Metabolism: Edaravone is primarily metabolized in the liver via sulfation and glucuronidation. The primary metabolite, edaravone sulfate, is also pharmacologically active.
- Elimination: Edaravone and its metabolites are primarily excreted in the urine. The terminal elimination half-life of edaravone is 4.5 to 6 hours. No dosage adjustment is necessary for mild to moderate hepatic or renal impairment.
Dosage
Standard Dosage
Adults:
- Intravenous: 60 mg infused over 60 minutes.
- Initial cycle: Daily dosing for 14 days, followed by a 14-day drug-free period.
- Subsequent cycles: Daily dosing for 10 days out of 14-day periods, followed by a 14-day drug-free period.
- Oral: 105 mg (5 mL) once daily in the morning after overnight fasting.
- Initial cycle: Daily dosing for 14 days, followed by a 14-day drug-free period.
- Subsequent cycles: Daily dosing for 10 days out of 14-day periods, followed by 14-day drug-free periods.
Children:
The safety and efficacy of edaravone in pediatric patients have not been established.
Special Cases:
- Elderly Patients: No dose adjustment is generally required, but close monitoring for adverse effects is recommended.
- Patients with Renal Impairment (mild to moderate): No dose adjustment is necessary. Severe renal impairment has not been studied.
- Patients with Hepatic Dysfunction (mild to moderate): No dose adjustment is necessary. Severe hepatic impairment has not been studied.
- Patients with Comorbid Conditions: Use with caution in patients with asthma or sulfite allergy due to the presence of sodium bisulfite in the intravenous formulation.
Clinical Use Cases
The primary clinical use case for edaravone is in the outpatient management of ALS. Dosing in intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations is not specifically indicated in the available literature.
Dosage Adjustments
Dose adjustments are generally not needed for elderly patients or those with mild to moderate hepatic or renal impairment.
Side Effects
Common Side Effects
- Bruising (contusion)
- Gait disturbance
- Headache
Rare but Serious Side Effects
- Hypersensitivity reactions (including anaphylaxis)
- Allergic reactions to sulfites (in IV formulation)
Long-Term Effects
Long-term effects of edaravone are not well-characterized due to the progressive nature of ALS.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include hypersensitivity reactions and anaphylaxis, which require immediate medical attention.
Contraindications
- Hypersensitivity to edaravone or any component of the formulation (especially sodium bisulfite in IV formulation)
Drug Interactions
No clinically significant drug interactions have been identified. In vitro studies suggest a low potential for interactions via CYP450 enzymes, UGT isoforms, or major transporters.
Pregnancy and Breastfeeding
- Pregnancy: Pregnancy Safety Category B3 (Australia). FDA category has not been assigned. Edaravone should generally be avoided during pregnancy due to potential risks to the fetus based on animal studies. If used, the patient should be informed of the potential hazards.
- Breastfeeding: Edaravone and its metabolites are excreted in rat milk. It is unknown whether edaravone is present in human milk. The developmental and health benefits of breastfeeding should be weighed against the mother’s need for the medication and the potential risks to the infant.
Drug Profile Summary
- Mechanism of Action: Free radical scavenger, protecting neurons from oxidative stress. The exact mechanism of action in ALS is unknown.
- Side Effects: Bruising, gait disturbance, headache, hypersensitivity reactions, sulfite allergy.
- Contraindications: Hypersensitivity to edaravone or any of its components.
- Drug Interactions: No clinically significant interactions reported.
- Pregnancy & Breastfeeding: Avoid during pregnancy if possible. Unknown safety during breastfeeding.
- Dosage: IV: 60 mg/day, Oral: 105 mg/day. Specific treatment cycles apply.
- Monitoring Parameters: Monitor for signs of hypersensitivity reactions (rash, hives, swelling, difficulty breathing). Periodic liver function tests may be considered.
Popular Combinations
Edaravone may be used concomitantly with riluzole, another medication approved for ALS.
Precautions
- General Precautions: Screen patients for hypersensitivity to edaravone or sulfites.
- Specific Populations: See sections on Pregnancy and Breastfeeding, Children, and Elderly patients.
- Lifestyle Considerations: No specific lifestyle considerations identified.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Edaravone?
A: IV: 60 mg daily infusion. Oral: 105 mg daily. See Dosage section for specifics on treatment cycles.
Q2: How does Edaravone work in ALS?
A: The precise mechanism is unknown, but it acts as a free radical scavenger, potentially protecting motor neurons from oxidative stress.
Q3: What are the most common side effects?
A: Bruising, gait disturbance, and headache.
Q4: Are there any serious side effects I should be aware of?
A: Yes, hypersensitivity reactions, including anaphylaxis, have been reported. Sulfite allergic reactions can occur with the IV formulation.
Q5: Can Edaravone be used during pregnancy or breastfeeding?
A: Edaravone should generally be avoided during pregnancy. Caution is advised if considering use during breastfeeding.
Q6: Are there any drug interactions with Edaravone?
A: No clinically significant drug interactions have been identified.
Q7: What should I monitor in patients receiving Edaravone?
A: Monitor closely for any signs of hypersensitivity reactions. Periodic liver function tests may be considered.
Q8: Can Edaravone be used in children?
A: The safety and efficacy in children have not been established.
Q9: How is Edaravone administered?
A: Edaravone is available for intravenous infusion and as an oral suspension.
Q10: Is any pre-treatment testing required before starting Edaravone?
A: While not routinely required, patients with known sulfite allergy should not receive the intravenous formulation. Assess renal and hepatic function for patients with known impairment.
