EVRYSDI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EVRYSDI (EVRYSDI).
SMN2 gene splicing modifier; increases production of full-length SMN protein by promoting inclusion of exon 7 in SMN2 mRNA transcripts.
| Metabolism | Hydrolysis by carboxylesterases (CES1, CES2) and subsequent glucuronidation by UGT1A1; CYP enzymes not involved. |
| Excretion | Primarily excreted unchanged in feces (75-80%) via biliary secretion; renal excretion is negligible (<2%). |
| Half-life | Terminal elimination half-life is 26-31 hours, supporting once-daily dosing. |
| Protein binding | Approximately 86-89% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Apparent volume of distribution is 3.0 L/kg, indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 19-30% (fed state). |
| Onset of Action | Oral: Clinical improvement in motor function observed within 4-6 weeks of initiating therapy. |
| Duration of Action | Duration of action is consistent with daily dosing; steady-state is achieved after approximately 1 week. Continuous therapy required to maintain effect. |
0.5 mg/kg orally once daily, maximum 20 mg/day
| Dosage form | FOR SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment; not studied in severe renal impairment (eGFR <30 mL/min/1.73m²) |
| Liver impairment | No dose adjustment for mild hepatic impairment (Child-Pugh class A); not recommended in moderate or severe hepatic impairment (Child-Pugh class B or C) |
| Pediatric use | Weight-based dosing: 0.5 mg/kg orally once daily; maximum 20 mg/day; for patients aged ≥2 months |
| Geriatric use | No specific dose adjustment; clinical studies did not include sufficient patients aged ≥65 years to determine if elderly respond differently |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EVRYSDI (EVRYSDI).
| Breastfeeding | No data on presence of risdiplam in human milk, effects on breastfed infant, or milk production. Animal studies show excretion in rat milk. M/P ratio not determined. Due to potential for serious adverse reactions in breastfeeding infants, advise patients not to breastfeed during treatment and for 1 month after last dose. |
| Teratogenic Risk | EVRYSDI (risdiplam) is not recommended during pregnancy due to potential fetal harm based on animal studies. In rats and rabbits, risdiplam caused embryofetal mortality, reduced fetal body weight, and skeletal variations at maternal exposures below the clinical exposure. There are no adequate human data. Risk cannot be excluded in the first trimester; second and third trimester risks are unknown but potential for adverse effects exists. |
■ FDA Black Box Warning
None
| Serious Effects |
Concomitant use with combined P-gp and BCRP inhibitors
| Precautions | ["Urinary tract infections","Upper respiratory tract infections","Pneumonia","Constipation","Weight loss","Vomiting","Headache","Pyrexia","Diarrhea","Arthralgia","Increased aminotransferases"] |
| Food/Dietary | Take with a fatty meal (≥20g fat) to increase absorption. Avoid grapefruit and Seville oranges (increase drug exposure). No other specific food restrictions. |
| Clinical Pearls |
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| Fetal Monitoring | If EVRYSDI is used during pregnancy, perform fetal ultrasound monitoring for growth and anatomy abnormalities. Monitor maternal liver function tests and renal function as per standard care. Report any suspected adverse reactions to the manufacturer. |
| Fertility Effects | In animal studies, risdiplam did not affect male or female fertility at doses up to 2.6 times (females) and 3.2 times (males) the human exposure at recommended dose. Human fertility effects unknown. Counsel patients on potential risks if planning pregnancy. |
| Monitor for hepatotoxicity and renal toxicity; obtain baseline and periodic LFTs and serum creatinine. Contraindicated in patients with pre-existing hepatic impairment (Child-Pugh B or C). Administer with fatty meal to enhance absorption. Avoid concurrent use with strong CYP3A4 inducers or inhibitors. May cause embryo-fetal harm; confirm pregnancy status prior to initiation. |
| Patient Advice | Take exactly as prescribed, once daily, with a meal containing fat (e.g., eggs, bacon, avocado). · Do not take if you have liver problems; inform your doctor of any history of liver disease. · Report any signs of liver injury (yellowing skin/eyes, dark urine, abdominal pain, nausea/vomiting). · Report any signs of kidney injury (decreased urine output, swelling in legs, fatigue). · Use effective contraception during treatment and for at least 1 month after stopping. · Do not take with grapefruit, Seville oranges, or products containing them. |