Genentech, Inc., a component of the Roche Group, manufactures risdiplam under the trade name Evrysdi.

For the treatment of people with spinal muscular atrophy, the FDA recently approved it.

Risdiplam (Evrysdi) Indications:

• Patients having spinal muscular atrophy who are at least 2 months old are eligible to receive treatment with it.

Evrysdi dose in Adults:

Note:

• Evrysdi is available as an oral solution. After reconstitution of the 60 mg solution, the strength of the solution is 0.75 mg/ml or 60 mg/80 ml.

Risdiplam (Evrysdi) Dose in Adults and Children:

The drug is administered orally (preferably after breakfast). Dosage recommendations are based on weight and age:

• older than two months but younger than two years: 
  • 0.2 mg/kg daily
• Age over 2 years old and weight over 20 kg:
  • 5 mg daily
• Age Over 2 years old and weighing under 20 kg:
  • 0.25 mg/kg daily

Missed Dose:

• In the event that a dose is skipped, it should be given as quickly as possible, ideally within six hours.
• Jump the dose and try taking the subsequent dose at the suggested time slot if it has been more than six hours.
• Don't give the patient another medication if they throw up or don't take the entire amount. At the appointed time, take the subsequent dose.
• Resume the next scheduled dose as usual.

Risdiplam (Evrysdi) Dose in Children:

The drug's effectiveness and tolerance in infants younger than 2 months just haven't been determined.

In older children, follow the same schedule as adults:

Dosage recommendations are based on weight and age:

• Older than two months but younger than two years:
  • 0.2 mg/kg daily
• Age over 2 years old and weight over 20 kg:
  • 5 mg daily
• Age Over 2 years old and weighing under 20 kg: 
  • 0.25 mg/kg daily

Missed Dose:

• Resume the next scheduled dose as usual.
• If it has been longer than six hours, miss the dose and consume the next one at the recommended time.
• In the event that a dose is missed, it should be given as quickly as possible, ideally within six hours.
• If the patient vomits or does not take the full dose, do not administer another dose. At the appointed time, take the subsequent dose.

Risdiplam (Evrysdi) Pregnancy Risk Category: N (Not assigned)

• The data available on the risks to human pregnancies from drug use are not sufficient to make an informed comment.
• Animal studies have shown adverse fetal outcomes, including fetal deaths, malformations, and reproductive impairment in offspring.
• It is important to inform females with reproductive potential about the possible adverse outcomes for their fetuses.
• Before initiating treatment, all females with reproductive potential should have a pregnancy check.
• Pregnant women with the potential to become pregnant should use reliable contraception throughout therapy and for at least a month after the final dosage.

Use during breastfeeding:

It is unknown whether the drug can be excreted into breast milk. In animal studies, however, it was found that breast milk was affected by the oral administration of the drug.

Manufacturers recommend weighing the risks to the infant from drug exposure and the benefits for the mother.

The drug's effect on fertility Studies on animals have demonstrated that both men and women can have negative impacts on the male and female reproductive systems, including those effects on germ cells.

Prior to starting therapy, patients with male patients may want to think about sperm preservation.

Risdiplam (Evrysdi) Dose in Renal Impairment:

No dosage adjustments have been mentioned in patients with renal impairment. 

Risdiplam (Evrysdi) Dose in Liver disease:

It has not been determined whether the medication is safe and effective for use in people with hepatic impairment.

However, drug exposure may increase in patients with liver disease. It should be avoided in patients with impaired hepatic functions. 

Risdiplam (Evrysdi) Side effects:

Common Side effects:

• Fever
• Upper respiratory tract infections
  • pharyngitis
  • rhinitis
  • nasopharyngitis
• Diarrhea
• Rash
  • erythematous rash
  • folliculitis
  • dermatitis
  • allergic rash
  • maculopapular rash
  • papular rash
• Pneumonia
• Constipation
• Vomiting

Less Common Side effects:

• Oral ulcers
• Arthralgias
• Urinary tract infections including cystitis.

Risdiplam (Evrysdi) Contraindications:

The manufacturer's labeling does not mention any contraindications

Risdiplam, Evrysdi Warnings and Precautions

• Carcinogenesis:
  • It is unknown whether the drug has any effect on carcinogenesis or mutagenesis. Take care.
• Toxicity to the retina:
  • In animal studies, functional and structural retinal abnormalities were observed. Use with caution.

Monitoring Parameters:

None is mentioned in the manufacturer's labeling. 

How to administer Risdiplam (Evrysdi)?

It is recommended to take the prescription once daily, usually shortly after one mealtime and at the same time every day.

Infants who have been breastfed should get the medication after nursing. Formula milk should not be combined with it.

Patients should be told to drink water after receiving medication in order for it to be completely absorbed.

The drug can also be administered via a nasogastric tube or a gastrostomy tube followed by flushing the tube with water.

It is important to use the reusable syringe that is provided with the drug for dose calculation and administration.

After evrysdi is drawn in a syringe, it should be administered immediately. If the drug is not administered within five minutes of drawing it in the syringe, it should be discarded.

When preparing the suspension, avoid inhaling the drug or direct exposure to the skin or mucous membranes. The pharmacist preparing the suspension should wear gloves.

The skin should be properly cleaned with water and soap after any contact. After reconstitution, the prepared suspension shouldn't be used for more than 64 days.

Risdiplam (Evrysdi) Mechanism of action:

In animal studies, it encourages the insertion of exon 7 in SMN2 mRNA transcripts. Additionally, the brain produces the complete SMN protein.

Risdiplam (survival motor neuron 2 modifiers) is an SMN2 modifier. It is utilized to cure spinal muscular atrophy in patients who have SMN protein deficiency due to a mutation on chromosome 5q.

Additional genes that are related to cell cycle regulation of apoptosis, such as FOXM1 or MADD, may also be spliced as a result of it.

Onset of action

• Within four weeks after treatment initiation, a greater than 2-fold increase of the SMN2 protein could occur.

Steady-state concentration with once-daily oral administration:

• 7 - 14 days.

The terminal elimination half-life:

• 50 hours in healthy adults.

Peak plasma concentration is reached at:

• 1 - 4 hours

Protein-binding:

• It is predominantly bound to albumin

Metabolism:

• Its metabolism is primarily controlled by CYPs 1A1, 2J2, 3A4, and 3A7, as well as flavin monooxygenases 1 and 3 (FMO1 and FMO3).

Drug excretion:

• Urine: 28% in urine (8% unaltered)
• Feces: 53% of the dose (14% unchanged)

Evrysdi (risdiplam) Drug Interaction:

Avoid using medications like metformin concurrently which are substrates for MATE transporters, which transport several medicines and toxins.

If the co-administration of the drug can not be avoided, monitor drug levels and drug-related toxicity. 

Risdiplam Brand Names (International):

• Evrysdi

Risdiplam Brand Names in Pakistan:

It is not available in Pakistan.