Risdiplamum
Risdiplamum Uses, Dosage, Side Effects, Food Interaction and all others data.
Risdiplamum is an orally bioavailable mRNA splicing modifier used for the treatment of spinal muscular atrophy (SMA). It increases systemic SMN protein concentrations by improving the efficiency of SMN2 gene transcription. This mechanism of action is similar to its predecessor nusinersen, the biggest difference being their route of administration: nusinersen requires intrathecal administration, as does the one-time gene therapy onasemnogene abeparvovec, whereas risdiplam offers the ease of oral bioavailability.
Risdiplamum was approved by the FDA in August 2020 for use in patients 2 months of age or older in the treatment of spinal muscular atrophy (SMA). Set to be substantially cheaper than other available SMA therapies, risdiplam appears to provide a novel and relatively accessible treatment option for patients with SMA regardless of severity or type.
Risdiplamum helps to alleviate symptoms of spinal muscular atrophy by stimulating the production of a critical protein in which these patients are deficient. Early trials with risdiplam demonstrated up to a 2-fold increase in SMN protein concentration in SMA patients after 12 weeks of therapy.
| Trade Name | Risdiplamum |
| Availability | Prescription only |
| Generic | Risdiplam |
| Risdiplam Other Names | Risdiplam, Risdiplamum |
| Related Drugs | Spinraza, Evrysdi, Zolgensma, nusinersen |
| Type | |
| Formula | C22H23N7O |
| Weight | Average: 401.474 Monoisotopic: 401.196408389 |
| Protein binding | Risdiplam is approximately 89% protein-bound in plasma, primarily to serum albumin. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Risdiplamum is an oral mRNA splicing modifier used in the treatment of spinal muscular atrophy (SMA).
Risdiplamum is indicated for the treatment of spinal muscular atrophy (SMA) in patients 2 months of age and older.
Risdiplamum is also used to associated treatment for these conditions: Spinal Muscular Atrophy (SMA)
How Risdiplamum works
Spinal muscular atrophy (SMA) is a severe and progressive congenital neuromuscular disease resulting from mutations in the survival of motor neuron 1 (SMN1) gene responsible for making SMN proteins. Clinical features of SMA include degeneration of motor neurons in the spinal cord which ultimately leads to muscular atrophy and, in some cases, loss of physical strength. SMN proteins are expressed ubiquitously throughout the body and are thought to hold diverse intracellular roles in DNA repair, cell signaling, endocytosis, and autophagy. A secondary SMN gene (SMN2) can also produce SMN proteins, but a small nucleotide substitution in its sequence results in the exclusion of exon 7 during splicing in approximately 85% of the transcripts - this means that only ~15% of the SMN proteins produced by SMN2 are functional, which is insufficient to compensate for the deficits caused by SMN1 mutations. Emerging evidence suggests that many cells and tissues are selectively vulnerable to reduced SMN concentrations, making this protein a desirable target in the treatment of SMA.
Risdiplamum is an mRNA splicing modifier for SMN2 that increases the inclusion of exon 7 during splicing, which ultimately increases the amount of functional SMN protein produced by SMN2. It does so by binding to two sites in SMN2 pre-mRNA: the 5' splice site (5'ss) of intron 7 and the exonic splicing enhancer 2 (ESE2) of exon 7.
Toxicity
Data regarding overdose of risdiplam are unavailable. Symptoms of overdose are likely to be consistent with risdiplam's adverse effect profile, and may therefore involve significant fever, diarrhea, and skin reactions.
Food Interaction
- Take after a meal.
- Take at the same time every day.
Risdiplamum Disease Interaction
Volume of Distribution
Following oral administration, risdiplam distributes well into the central nervous system and peripheral tissues. The apparent volume of distribution at steady-state is 6.3 L/kg.
Elimination Route
The Tmax following oral administration is approximately 1-4 hours. Following once-daily administration with a morning meal (or after breastfeeding), risdiplam reaches steady-state in approximately 7-14 days. The pharmacokinetics of risdiplam were found to be approximately linear between all studied dosages in patients with SMA.
Half Life
The terminal elimination half-life of risdiplam is approximately 50 hours in healthy adults.
Clearance
For a 14.9kg patient, the apparent clearance of risdiplam is 6.3 L/kg.
Elimination Route
Following the oral administration of 18mg risdiplam, approximately 53% of the dose was excreted in the feces and 28% was excreted in the urine. Unchanged parent drug comprised 14% of the dose excreted in feces and 8% of the dose excreted in urine.
Innovators Monograph
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