Risdiplam is indicated for the treatment of spinal muscular atrophy (SMA) in both pediatric and adult patients.

Risdiplam is a survival motor neuron 2 (SMN2) splicing modifier developed for the treatment of spinal muscular atrophy (SMA) caused by mutations in chromosome 5q that result in deficiency of SMN protein. In vitro studies and transgenic animal models have shown that risdiplam increases the inclusion of exon 7 in SMN2 messenger RNA (mRNA) transcripts, leading to increased production of full-length SMN protein in the brain. Preclinical data from in vitro and in vivo studies suggest that risdiplam may also affect alternative splicing of other genes, including FOXM1 and MADD. FOXM1 is associated with regulation of the cell cycle, while MADD is involved in apoptosis. These gene effects have been considered as potential contributors to adverse effects observed in animal studies.

Dose Preparation: It is recommended that a healthcare provider discuss with the patient or caregiver how to prepare the prescribed daily dose prior to administration of the first dose. Instruct patients or caregivers to prepare the dose using the reusable oral syringe provided. Risdiplam must be taken immediately after it is drawn up into the oral syringe. If Risdiplam is not taken within 5 minutes, Risdiplam should be discarded from the oral syringe, and a new dose should be prepared.

Dose Administration: Risdiplam is taken orally once daily after a meal at approximately the same time each day. In infants who are breastfed, Risdiplam should be administered after breastfeeding. Risdiplam cannot be mixed with formula or milk. Instruct patients to drink water after taking Risdiplam to ensure the drug has been completely swallowed. If the patient is unable to swallow and has a nasogastric or gastrostomy tube, Risdiplam can be administered via the tube. The tube should be flushed with water after delivering Risdiplam.

Risdiplam is administered orally once daily. The recommended dosage is determined by age and body weight.

• Less than 2 months of age: 0.15 mg/kg
• 2 months to less than 2 years of age: 0.2 mg/kg
• 2 years of age and older weighing less than 20 kg: 0.25 mg/kg
• 2 years of age and older weighing 20 kg or more: 5 mg

Avoid co-administration of Risdiplam with drugs that are substrates of multidrug and toxin extrusion (MATE) transporters.

In patients with later-onset SMA, the most commonly reported adverse reactions (≥10% incidence and more frequent than placebo/control) include fever, diarrhea, and skin rash. In infantile-onset SMA patients, similar adverse reactions were observed. Additional common side effects (≥10% incidence) include upper respiratory tract infection, lower respiratory tract infection, constipation, vomiting, and cough.

There are no adequate human data regarding developmental risk with risdiplam use during pregnancy. No data are available on the presence of risdiplam in human breast milk, its effects on the breastfed infant, or its effects on milk production. However, risdiplam has been shown to be excreted in the milk of lactating rats.

Pediatric Use: The safety and effectiveness of Risdiplam have been established in pediatric patients, including neonates and older children.

Geriatric Use: Clinical studies did not include sufficient numbers of patients aged 65 years and above to determine whether they respond differently from younger adults.

Store dry powder at 20°C to 25°C. Keep out of reach of children.