Version May 2024
Spinal muscular atrophy : Oral: 5 mg once daily.
Missed dose:
≤6 hours since usual administration: Administer as soon as possible and resume usual dosing schedule the next day.
>6 hours since usual administration: Skip missed dose and administer next dose at usual administration time the next day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, renal impairment is not expected to alter exposure to risdiplam.
Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment needed.
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
(For additional information see "Risdiplam: Pediatric drug information")
Spinal muscular atrophy (SMA):
Infants <2 months: Oral: 0.15 mg/kg/dose once daily.
Infants ≥2 months and Children <2 years: Oral: 0.2 mg/kg/dose once daily.
Children ≥2 years and Adolescents:
<20 kg: Oral: 0.25 mg/kg/dose once daily.
≥20 kg: Oral: 5 mg once daily.
There are no dosage adjustments provided in the manufacturer's labeling; however, renal impairment is not expected to alter exposure to risdiplam.
Mild to moderate impairment: No dosage adjustment needed based on data in patients ≥20 kg.
Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Skin rash (17%; including allergic dermatitis, erythema of skin, erythematous rash, folliculitis, maculopapular rash, papular rash)
Gastrointestinal: Constipation (infants: ≥10%), diarrhea (17%), vomiting (infants: ≥10%)
Respiratory: Pneumonia (infants: ≥10%), upper respiratory tract infection (infants: ≥10%; including nasopharyngitis, rhinitis)
Miscellaneous: Fever (22%; including hyperpyrexia)
1% to 10%:
Gastrointestinal: Aphthous stomatitis (≤7%), oral mucosa ulcer (≤7%)
Genitourinary: Urinary tract infection (5%)
Neuromuscular & skeletal: Arthralgia (5%)
There are no contraindications listed in the US manufacturer's labeling.
Canadian labeling: Hypersensitivity to risdiplam or any component of the formulation.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP 1997; CDC 1982); some data suggest that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Oral:
Evrysdi: 0.75 mg/mL (80 mL) [contains edetate (edta) disodium dihydrate, polyethylene glycol (macrogol), sodium benzoate; strawberry flavor]
No
Solution (reconstituted) (Evrysdi Oral)
0.75 mg/mL (per mL): $192.23
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Oral:
Evrysdi: 0.75 mg/mL (80 mL) [contains edetate (edta) disodium dihydrate, polyethylene glycol (macrogol), sodium benzoate]
Oral: Administer after a meal at approximately the same time each day. In infants who are breastfed, administer after breastfeeding. Do not mix with formula or milk. Instruct patients to drink water after taking dose to ensure it has been completely swallowed. If patient is unable to swallow, dose may be administered through a nasogastric or gastrostomy tube. Flush tube with water following administration. Prepare dose using the reusable oral syringe provided. Administer immediately after drawing up into oral syringe. If dose is not administered within 5 minutes, discard from the oral syringe and prepare a new dose. If vomiting occurs following dose or dose is not fully swallowed, another dose should not be administered; next dose should be administered at next regularly scheduled time.
Oral: Prepare dose only using the provided reusable oral syringe; do not use household tablespoon or other measuring device. Administer immediately after drawing up into oral syringe. If dose is not administered within 5 minutes, discard from the oral syringe and prepare a new dose. Wash syringe after each use.
Administer at the same time each day after a meal or feeding. Do not mix with milk or formula. Administer 15 mL of water after administration to ensure dose is completely swallowed. If unable to swallow, dose may be administered through an NG or gastrostomy tube. Flush tube with 10 to 20 mL of water following administration. If dose is not fully swallowed or vomiting occurs after administration, do not administer another dose; resume regular schedule the following day.
Missed dose:
If a dose is missed ≤6 hours from the usual time it is taken, take the dose as soon as possible.
If >6 hours have passed since the missed dose, do NOT take the missed dose; resume regular schedule the following day.
Spinal muscular atrophy: Treatment of spinal muscular atrophy in pediatric and adult patients.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.
Substrate of BCRP/ABCG2
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
MATE1/2-K Substrates (Clinically Relevant with Inhibitors): Risdiplam may increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of risdiplam with MATE substrates if possible. If the combination cannot be avoided, monitor closely for adverse effects. Consider a reduced dose of the MATE substrate according to that substrate's labeling if appropriate. Risk D: Consider therapy modification
Evaluate pregnancy status prior to use in patients who could become pregnant.
Patients who could become pregnant should use effective contraception during therapy and for at least 1 month after the last risdiplam dose.
Adverse effects to male reproductive function and fertility were observed in animal toxicology studies; males of reproductive potential may want to consider sperm preservation prior to risdiplam therapy.
Based on data from animal reproduction studies, in utero exposure to risdiplam may cause fetal harm.
Data collection to monitor pregnancy and infant outcomes following exposure to risdiplam is ongoing. Health care providers are encouraged to enroll patients exposed to risdiplam during pregnancy in the pregnancy registry (833-760-1098). Patients may also enroll themselves.
It is not known if risdiplam is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Treats spinal muscular atrophy caused by mutations in chromosome 5q that lead to survival motor neuron (SMN) protein deficiency; exerts effect by increasing exon 7 inclusion in SMN2 messenger ribonucleic acid transcripts and production of full-length SMN protein.
Distribution: Vdss: 6.3 L/kg.
Protein binding: ~89%, primarily to albumin.
Metabolism: Primarily hepatic via flavin monooxygenase 1 and 3 (FMO1 and FMO3); also metabolized by CYP1A1, 2J2, 3A4, and 3A7; forms inactive metabolite M1.
Half-life elimination: ~50 hours.
Time to peak: 1 to 4 hours.
Excretion: Feces: ~53% (14% as unchanged drug); urine: 28% (8% as unchanged drug).
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