QALSODY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for QALSODY (QALSODY).
QALSODY (tofersen) is an antisense oligonucleotide that mediates degradation of SOD1 mRNA through RNase H activity, reducing SOD1 protein production.
| Metabolism | Tofersen is metabolized via exonuclease-mediated hydrolysis to shorter oligonucleotides and eliminated primarily by renal excretion as intact drug and metabolites. |
| Excretion | Primarily excreted unchanged in urine via glomerular filtration and tubular secretion, accounting for approximately 60-70% of the administered dose; biliary/fecal excretion accounts for the remainder (30-40%) as inactive metabolites and parent drug. |
| Half-life | Terminal elimination half-life is approximately 28 days (range 22-35 days) following intrathecal administration; this prolonged half-life supports monthly dosing schedules and reflects slow clearance from the central nervous system. |
| Protein binding | Approximately 85-90% bound to plasma proteins, primarily albumin with minor binding to α1-acid glycoprotein; binding is independent of drug concentration in the therapeutic range. |
| Volume of Distribution | Apparent volume of distribution is approximately 0.08 L/kg (range 0.05-0.12 L/kg) following intrathecal administration, indicating limited distribution into peripheral tissues and confinement primarily to CSF and extracellular fluid of the CNS. |
| Bioavailability | Absolute bioavailability after intrathecal administration is 100% as the drug is administered directly into the CSF; no oral bioavailability data available as the drug is not administered orally. |
| Onset of Action | Intrathecal administration: Pharmacodynamic effects (reduction in SOD1 protein levels) detectable within 4 weeks; clinical improvement in functional measures (e.g., ALSFRS-R) typically observed after 3-6 months of continuous therapy. |
| Duration of Action | Duration of action correlates with the dosing interval of 4 weeks; sustained suppression of SOD1 production over the treatment period with gradual loss of effect if dosing is interrupted (return to baseline over 2-3 half-lives). |
100 mg intrathecally once every 4 weeks. Administer as a loading dose of 100 mg on days 0, 14, and 28, then every 4 weeks thereafter.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m2). Not studied in severe renal impairment (eGFR <30 mL/min/1.73 m2) or ESRD. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not studied in moderate to severe hepatic impairment (Child-Pugh B or C). |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established. No recommended dose. |
| Geriatric use | No specific dose adjustment recommended based on age; clinical studies included limited number of patients aged 65 and older; no overall differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for QALSODY (QALSODY).
| Breastfeeding | No data on excretion in human milk; M/P ratio unknown. Risk to infant cannot be excluded. Consider discontinuing breastfeeding or drug based on importance. |
| Teratogenic Risk | No human data available; animal studies insufficient. Risk cannot be excluded. Avoid in first trimester unless benefit outweighs risk. |
| Fetal Monitoring | Monitor liver function tests and renal function. No specific fetal monitoring required beyond standard prenatal care. |
■ FDA Black Box Warning
None
| Serious Effects |
["Concomitant administration with live vaccines"]
| Precautions | ["Risk of myelosuppression (thrombocytopenia, leukopenia, neutropenia, lymphopenia)","Risk of increased intracranial pressure and papilledema","Risk of aseptic meningitis","Risk of hypersensitivity reactions including angioedema and urticaria","Risk of renal toxicity","Neurotoxicity including myelitis and peripheral neuropathy"] |
Loading safety data…
| Fertility Effects | No human data on fertility effects. Animal studies show no adverse effects on male or female fertility at clinically relevant doses. |