risdiplam

General

Pronunciation:
ris-diplam


Trade Name(s)

  • Evrysdi

Ther. Class.

none assigned

Pharm. Class.

survival of motor neuron 2 splicing modifiers

Indications

Spinal muscular atrophy.

Action

Acts as a survival of motor neuron 2 (SMN2) splicing modifier, which facilitates production of full-length SMN in patients with spinal muscular atrophy caused by genetic mutations leading to SMN protein deficiency.

Therapeutic Effect(s):

  • Improvement in ability to sit without support and improvement in survival without requiring permanent ventilation in infantile-onset spinal muscular atrophy.
  • Improved motor function in later-onset spinal muscular atrophy.

Pharmacokinetics

Absorption: Well absorbed following oral administration.

Distribution: Extensively distributed to extravascular tissues.

Metabolism and Excretion: Primarily metabolized by flavin monooxygenase 1 and 3 as well as the CYP1A1, CYP2J2, CYP3A4, and CYP3A7 isoenzymes. Primarily excreted in feces (53%; 14% as unchanged drug), with 28% excreted in urine (8% as unchanged drug).

Half-life: 50 hr.

TIME/ACTION PROFILE (plasma concentrations)

ROUTEONSETPEAKDURATION
POunknown1–4 hrunknown

Contraindication/Precautions

Contraindicated in:

  • None.

Use Cautiously in:

  • Severe hepatic impairment;
  • Rep:   Women of reproductive potential;
  • OB:  Safety not established in pregnancy;
  • Lactation:  Safety not established in breastfeeding.

Adverse Reactions/Side Effects

Derm: rash

EENT: nasopharyngitis, rhinitis, upper respiratory tract infection

GI: constipation, diarrhea, vomiting, mouth ulcers

GU: ↓ fertility (males), urinary tract infection

MS: arthralgia

Resp: pneumonia

Misc: fever

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

May ↑ levels and risk of toxicity of  metformin ; avoid concurrent use.

Route/Dosage

PO (Adults and Children ≥2 yr and ≥20 kg): Tablet or oral solution: 5 mg once daily.

PO (Adults and Children ≥2 yr and <20 kg): Oral solution: 0.25 mg/kg once daily.

PO (Children 2 mo–<2 yr): Oral solution: 0.2 mg/kg once daily.

PO (Children <2 mo): Oral solution: 0.15 mg/kg once daily.

Availability

Tablets: 5 mg

Powder for oral solution (strawberry flavor): 0.75 mg/mL

Assessment

  • Assess symptoms of spinal muscular dystrophy (muscle weakness and ↓ muscle tone, limited mobility, breathing problems, problems eating and swallowing, delayed gross motor skills, spontaneous tongue movements) before and periodically during therapy.

Implementation

  • PO Administer with or without food at the same time each day.
    • Administer before or after breastfeeding. Do not mix with formula or milk.
    • Tablets:  DNC: Swallow tables whole. Do not chew, cut, or crush.  If unable to swallow tablet whole, disperse tablet in 5 mL of room-temperature, non-chlorinated drinking water. Gently swirl for 3 min until dispersed (few particles may remain). Administer immediately. Rinse cup with ≥15 mL of non-chlorinated drinking water, swirl, and administer. If dispersed, solution must be taken within 10 min; discard if not used. Do not expose dispersion to sunlight or mix with any other liquid. Do not administer prepared dispersion via nasogastric or gastrostomy tube.
    • Oral Solution: Use provided reusable oral syringe. Administer immediately after drawing into syringe. If not taken within 5 min, discard and prepare a new dose. Advise patient to drink water after dose to ensure full swallow. Store in refrigerator and discard any unused portion 64 days after constitution.  If unable to swallow, may be given via nasogastric or gastrostomy tube. Flush tube before and after administration.

Patient/Family Teaching

  • Explain purpose and side effects of medication to patient. Advise patient to read  Patient Information  before starting therapy. Advise patient/caregiver in correct administration technique. Administer missed doses as soon as possible if within 6 hr of missed dose; then resume dosing schedule next day. Otherwise, omit missed dose and resume regular scheduled next day. If dose is not fully swallowed or vomiting occurs after taking a dose, omit dose; do not administer to make up for lost dose.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • Advise patient/caregiver that risdiplam oral solution should come from the pharmacy as a liquid that can be given by mouth or through a feeding tube. The liquid solution is prepared by pharmacist. If the medicine in the bottle is a powder, do not use it. Contact your pharmacist for a replacement. Tablets should not be given through a feeding tube.
  • Advise patient/caregiver to avoid getting risdiplam on skin or in eyes. If risdiplam gets on skin, wash the area with soap and water. If risdiplam gets in eyes, rinse eyes with water.

Rep:   May cause fetal harm. Advise women to notify health care professional immediately if pregnancy is planned or suspected or if breastfeeding. Advise women of reproductive potential to use effective contraception during and for 1 mo after last dose. May impair male fertility; may consider sperm preservation prior to treatment. Encourage pregnant patients to enroll in registry that monitors outcomes of women exposed to risdiplam during pregnancy by contacting 1-833-760-1098 or visit https://www.evrysdipregnancyregistry.com.

Evaluation/Desired Outcomes

  • Improvement in ability to sit without support and improvement in survival without requiring permanent ventilation in infantile-onset spinal muscular atrophy.
  • Improved motor function in later-onset spinal muscular atrophy.