OHTUVAYRE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OHTUVAYRE (OHTUVAYRE).
OHTUVAYRE is an antisense oligonucleotide that binds to the survival motor neuron 2 (SMN2) pre-mRNA, altering splicing to increase production of full-length survival motor neuron (SMN) protein.
| Metabolism | Metabolized via endonuclease-mediated hydrolysis to shorter oligonucleotides; not a substrate for CYP450 enzymes. |
| Excretion | Primarily renal excretion as unchanged drug: 70-80% in urine, with approximately 20% in feces via biliary elimination. |
| Half-life | Terminal elimination half-life is approximately 20 hours (range 15-25 h), supporting once-daily dosing. |
| Protein binding | Approximately 99% bound to plasma proteins, mainly albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is about 5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 90%, with minimal first-pass metabolism. |
| Onset of Action | Not applicable; OHTUVAYRE (vamorolone) does not have an immediate clinical effect. Steady-state concentrations are reached after ~5 days of daily dosing. |
| Duration of Action | Duration of action is consistent with its half-life, providing therapeutic effects over 24 hours with once-daily administration. |
| Molecular Weight | 432.5 |
OHTUVAYRE (vadadustat) is administered orally at a starting dose of 300 mg once daily. The dose may be titrated based on hemoglobin response in increments of 150 mg up to a maximum of 600 mg once daily.
| Dosage form | SUSPENSION |
| Renal impairment | No dose adjustment is required for patients with mild to severe renal impairment, including those on dialysis. |
| Liver impairment | No dose adjustment recommended for mild hepatic impairment (Child-Pugh A). For moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment, use is not recommended due to lack of data. |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established. No dosage recommendations are available. |
| Geriatric use | No specific dose adjustment required based on age alone. Monitor hemoglobin and iron stores as clinically appropriate. |
| 1st trimester | Contraindicated due to known teratogenicity; high risk of severe birth defects. |
| 2nd trimester | Contraindicated due to risk of fetal harm. |
| 3rd trimester | Contraindicated due to risk of fetal harm and potential neonatal toxicity. |
Clinical note
Comprehensive clinical and safety monograph for OHTUVAYRE (OHTUVAYRE).
| Placental transfer | Significant placental transfer documented; crosses the placenta readily. |
| Breastfeeding | Excretion into breast milk is unknown; however, due to potential for serious adverse effects, breastfeeding is contraindicated during treatment. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
PregnancyBreastfeedingHypersensitivity to active substance or any excipient
| Precautions | Thrombocytopenia and coagulation abnormalities, Renal toxicity including glomerulonephritis, Hydrocephalus, Hypersensitivity reactions, Neurologic complications (e.g., meningitis, myelitis) |
| Food/Dietary | No significant food-drug interactions known. Avoid grapefruit and grapefruit juice as they may affect drug metabolism (though not specifically studied for vutrisiran, it's a general precaution for many medications). Maintain adequate vitamin A intake through diet or supplements as directed. |
| Clinical Pearls |
Loading safety data…
| L5 |
| Teratogenic Risk | OHTUVAYRE (vutrisiran) is an RNAi therapeutic targeting transthyretin. Animal studies have not shown teratogenicity, but human data are lacking. First trimester: insufficient data; second and third trimesters: no known risks, but use only if benefit outweighs risk due to lack of human trials. |
| Fetal Monitoring | Monitor for adverse effects including hepatic function (ALT, AST), renal function, and infusion-related reactions. Fetal monitoring: standard prenatal care with ultrasound for growth and anatomy if exposure occurs. No specific fetal monitoring required based on known data. |
| Fertility Effects | Animal studies show no impairment of male or female fertility. Human data not available. No known effect on reproductive function. |
| OHTUVAYRE (vutrisiran) is a transthyretin-directed small interfering RNA indicated for polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR). Administer subcutaneously once every 3 months. Monitor for injection site reactions and vitamin A levels (supplement with vitamin A if needed). Avoid use in patients with severe renal impairment (eGFR <30 mL/min) or moderate-to-severe hepatic impairment. |
| Patient Advice | This medication is given as an injection under the skin every 3 months by a healthcare professional. · Common side effects include injection site redness, pain, or swelling; nausea; and joint pain. · You may need to take vitamin A supplements because this medicine can lower vitamin A levels. · Report any signs of infection, unusual bleeding, or severe allergic reactions (rash, difficulty breathing) immediately. · Do not miss your scheduled doses; keep all appointments for injections. |