resmetirom

Therapeutic Classification: none assigned

Pharmacologic Classification:

Indications ⬆ ⬇

REMS

Noncirrhotic nonalcoholic steatohepatitis with moderate to advanced liver fibrosis (in combination with diet and exercise).

Action ⬆ ⬇

Acts as a partial agonist of the thyroid hormone receptor beta, which reduces the production of triglycerides in the liver.

Therapeutic effects:

Improvement in steatohepatitis and/or liver fibrosis.

Pharmacokinetics ⬆ ⬇

Absorption: Extent of absorption following oral administration unknown.

Distribution: Well distributed to tissues.

Protein Binding: >99%.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP2C8 isoenzyme to an active metabolite. 67% excreted in feces (as metabolites); 24% excreted in urine (<1% as unchanged drug).

Half-Life: 4.5 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	4 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Moderate to severe hepatic impairment.

Use Cautiously in:

Severe renal impairment;
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: arrhythmias, palpitations

Derm: pruritus, erythema

Endo: hypoglycemia

GI: ↓appetite, ↑liver enzymes, diarrhea, nausea, abdominal pain, abnormal feces, cholecystitis, cholelithiasis, constipation, flatulence, obstructive pancreatitis, vomiting

GU: uterine bleeding

MS: tendinopathy

Neuro: depression, dizziness, dysgeusia, vertigo

Misc: hypersensitivity reactions

Interactions ⬆ ⬇

Drug-drug:

Strong CYP2C8 inhibitors, including gemfibrozil, or moderate CYP2C8 inhibitors, including clopidogrel, may ↑ levels and risk of toxicity; avoid concurrent use with strong CYP2C8 inhibitors and ↓ resmetirom dose when used with moderate CYP2C8 inhibitors.
Organic anion-transporting polypeptides (OATP) 1B1 inhibitors and OATP 1B3 inhibitors, including cyclosporine, may ↑ levels and risk of toxicity; avoid concurrent use.
May ↑ levels and risk of toxicity of atorvastatin, pravastatin, rosuvastatin, and simvastatin; do not exceed 20 mg/day of rosuvastatin or simvastatin or 40 mg/day of atorvastatin or pravastatin.
May ↑ levels and risk of toxicity of CYP2C8 substrates.

Route/Dosage ⬆ ⬇

PO (Adults ≥100 kg): 100 mg once daily. Concurrent use of moderate CYP2C8 inhibitor: 80 mg once daily.
PO (Adults <100 kg): 80 mg once daily. Concurrent use of moderate CYP2C8 inhibitor: 60 mg once daily.

Availability ⬆ ⬇

Tablets: 60 mg; 80 mg; 100 mg

Assessment ⬆ ⬇

Monitor weight and BMI before and periodically during therapy.
Assess for signs/symptoms of hepatotoxicity (fatigue, nausea, vomiting, right upper quadrant pain or tenderness, jaundice, fever, rash, eosinophilia).
Assess for signs/symptoms of cholelithiasis, acute cholecystitis, and obstructive pancreatitis (gallstone). If cholelithiasis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated. If an acute gallbladder event is suspected, hold resmetirom until resolved.

Lab Test Considerations:

Monitor ALT, AST, and total bilirubin levels before and during therapy.
Monitor cholesterol, triglycerides, LDL-C, and HDL-C.
Perform TSH, free T3, and T4 levels.

Implementation ⬆ ⬇

PO: Administer with or without food.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
Inform patients of the risk of hepatotoxicity, cholelithiasis, cholecystitis, and obstructive pancreatitis (gallstones). Instruct patient to immediately report any signs/symptoms to health care provider.
Inform patients that concurrent use of resmetirom with some statins may ↑ the risk of statin-related adverse reactions (↑ liver enzymes, myopathy, rhabdomyolysis).
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇