ATTRUBY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ATTRUBY (ATTRUBY).
ATTRUBY (acoramidis) is a transthyretin (TTR) stabilizer that binds to TTR, preventing its dissociation into monomers and subsequent amyloid fibril formation in tissues.
| Metabolism | Metabolized primarily by CYP3A4 and to a lesser extent by CYP2C8 and CYP2C9. |
| Excretion | Primarily hepatic metabolism with biliary-fecal elimination (approximately 63% in feces as metabolites). Renal excretion accounts for about 23% of the dose (mostly as metabolites), with <1% unchanged in urine. |
| Half-life | Elimination half-life is approximately 17-20 hours in healthy subjects, supporting once-daily dosing. In patients with hepatic impairment, half-life may be prolonged. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution is approximately 12 L (0.17 L/kg in a 70 kg adult), indicating limited extravascular distribution and confinement to plasma and interstitial fluid. |
| Bioavailability | Oral bioavailability is approximately 30-40% due to first-pass metabolism. Administration with food increases exposure by 20-30%. |
| Onset of Action | Oral administration: clinical effect (reduction in liver stiffness or fibrosis markers) observed within 4-8 weeks; maximal effect may require 12-24 weeks of continuous therapy. |
| Duration of Action | Duration of action persists for the dosing interval (24 hours) with sustained pharmacodynamic effect. Clinical effects are reversible upon discontinuation. |
IV 30 mg/kg once every 3 weeks until disease progression or unacceptable toxicity.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (CrCl <30 mL/min) or ESRD. |
| Liver impairment | No dose adjustment recommended for mild hepatic impairment (Child-Pugh A). Not studied in moderate or severe hepatic impairment (Child-Pugh B or C). |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustments recommended; elderly patients may have reduced renal function; monitor closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ATTRUBY (ATTRUBY).
| Breastfeeding | There are no data on the presence of vutrisiran in human milk, effects on the breastfed infant, or effects on milk production. Vutrisiran is a small interfering RNA (siRNA) oligonucleotide, and because of the potential for serious adverse reactions in nursing infants, advise women not to breastfeed during treatment and for at least 6 months after the last dose. |
| Teratogenic Risk | Based on animal studies, ATTRUBY (vutrisiran) may cause fetal harm when administered to pregnant women. There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, subcutaneous administration of vutrisiran to pregnant rats during organogenesis resulted in embryofetal mortality and reduced fetal body weights at doses equivalent to approximately 8 times the recommended human dose. Advise pregnant women of the potential risk to the fetus. The drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. |
■ FDA Black Box Warning
None
| Serious Effects |
["Known hypersensitivity to acoramidis or any excipients.","Severe hepatic impairment (Child-Pugh class C)."]
| Precautions | ["Monitor for signs of volume depletion or hypotension due to potential diuretic effect.","Use with caution in patients with hepatic impairment (Child-Pugh class B or C) as exposure may increase.","Monitor liver function tests periodically.","Potential drug interactions with strong CYP3A4 inhibitors or inducers."] |
| Food/Dietary | No specific food restrictions, but avoid grapefruit juice due to potential CYP3A4 inhibition. Maintain adequate hydration to manage diarrhea. |
Loading safety data…
| Fetal Monitoring | If ATTRUBY is administered during pregnancy, or if a patient becomes pregnant while receiving the drug, apprise the patient of the potential hazard to the fetus. Monitor pregnant women for adverse effects of the drug, including but not limited to: liver function tests, renal function, complete blood counts, and signs of hypersensitivity reactions. Conduct periodic fetal ultrasound to assess fetal growth and amniotic fluid volume. Consider consultation with a maternal-fetal medicine specialist. |
| Fertility Effects | No human data on the effect of vutrisiran on fertility are available. In animal studies, no adverse effects on male or female fertility were observed in rats at subcutaneous doses up to 10 mg/kg (approximately 8 times the recommended human dose based on AUC). It is unknown whether the drug affects human fertility. |
| Clinical Pearls |
| ATTRUBY (copanlisib) is a PI3K inhibitor for relapsed follicular lymphoma. Monitor for hypertension and hyperglycemia; premedicate with antihistamines to reduce infusion reactions. Dose adjustments required for hepatic impairment. |
| Patient Advice | Report signs of infection, bleeding, or severe diarrhea immediately. · Monitor blood pressure regularly as hypertension is common. · Avoid pregnancy; use effective contraception during and for 1 month after treatment. · Inform your doctor if you have diabetes; blood sugar may increase. · Take anti-nausea medication as prescribed to manage gastrointestinal side effects. |