ORGATRAX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ORGATRAX (ORGATRAX).

How it works

ORGATRAX (letermovir) inhibits the cytomegalovirus (CMV) DNA terminase complex, preventing viral DNA processing and packaging.

What the body does with it

Metabolism	Primarily metabolized by UGT1A1/1A3, with minor contributions from CYP3A4.
Excretion	Primarily hepatic metabolism with renal excretion of metabolites. Approximately 30% of a dose is excreted unchanged in urine; the remainder is eliminated via feces (biliary excretion) after glucuronidation in the liver.
Half-life	Terminal elimination half-life is 6–8 hours in adults with normal renal and hepatic function. In elderly patients or those with hepatic impairment, half-life may be prolonged up to 12–15 hours, requiring dose adjustment.
Protein binding	Approximately 78–82% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Vd is 3–5 L/kg, indicating extensive tissue distribution. This large Vd suggests significant extravascular binding and accumulation in tissues such as lung and liver.
Bioavailability	Oral bioavailability is approximately 40–60% due to first-pass metabolism. Intramuscular bioavailability is near 100%.
Onset of Action	Oral: Onset of clinical effect occurs within 30–60 minutes for antihistaminic effects. For sedative effects, onset is 15–30 minutes. Intravenous: Onset within 5–10 minutes.
Duration of Action	Duration of antihistaminic effect is 4–6 hours; sedative effects last 6–8 hours. Clinical duration may be shorter in children and longer in elderly due to altered clearance.

Classification & Brands

Dosing & administration

Hydroxyzine pamoate (Orgatrax) 25-100 mg orally every 6-8 hours as needed; maximum 600 mg/day.

Dosage form	INJECTABLE
Renal impairment	For GFR <50 mL/min: administer 25 mg orally every 12 hours; monitor for excessive sedation.
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh B or C: initiate at 25 mg every 12 hours and titrate cautiously due to reduced clearance.
Pediatric use	Children ≥6 years: 0.5-1 mg/kg orally every 6-8 hours; maximum 50 mg/day. Children <6 years: 0.5 mg/kg orally every 6-8 hours; maximum 25 mg/day.
Geriatric use	Initiate at 25 mg orally every 8 hours; increase slowly due to increased risk of anticholinergic effects, sedation, and falls.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ORGATRAX (ORGATRAX).

Breastfeeding	Excreted in breast milk; M/P ratio not established. Potential for serious adverse reactions in nursing infants (e.g., renal toxicity, hypotonia). Decision to discontinue nursing or drug based on importance of drug to mother.
Teratogenic Risk	FDA Pregnancy Category D (based on animal studies and limited human data). First trimester: increased risk of major malformations (cardiac, CNS), spontaneous abortion. Second/third trimester: risk of fetal growth restriction, oligohydramnios, neonatal renal impairment. Avoid in pregnancy unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warning.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Concomitant use with pimozide, ergot alkaloids, or HMG-CoA reductase inhibitors (simvastatin, lovastatin).","Hypersensitivity to letermovir or any component of the formulation."]

Clinical Precautions

Precautions

["Hepatotoxicity: monitor liver function tests.","Drug interactions: potent CYP3A4 inducers (e.g., rifampin) reduce letermovir exposure; coadministration with pimozide, ergot alkaloids, or HMG-CoA reductase inhibitors (simvastatin, lovastatin) contraindicated.","Embryo-fetal toxicity: advise females of reproductive potential to use effective contraception during treatment and for 2 weeks after last dose.","Hypersensitivity reactions."]

Clinical Tips & Counseling

Drug interactions

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ORGATRAX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ORGATRAX (ORGATRAX).

How it works

ORGATRAX (letermovir) inhibits the cytomegalovirus (CMV) DNA terminase complex, preventing viral DNA processing and packaging.

What the body does with it

Metabolism	Primarily metabolized by UGT1A1/1A3, with minor contributions from CYP3A4.
Excretion	Primarily hepatic metabolism with renal excretion of metabolites. Approximately 30% of a dose is excreted unchanged in urine; the remainder is eliminated via feces (biliary excretion) after glucuronidation in the liver.
Half-life	Terminal elimination half-life is 6–8 hours in adults with normal renal and hepatic function. In elderly patients or those with hepatic impairment, half-life may be prolonged up to 12–15 hours, requiring dose adjustment.
Protein binding	Approximately 78–82% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Vd is 3–5 L/kg, indicating extensive tissue distribution. This large Vd suggests significant extravascular binding and accumulation in tissues such as lung and liver.
Bioavailability	Oral bioavailability is approximately 40–60% due to first-pass metabolism. Intramuscular bioavailability is near 100%.
Onset of Action	Oral: Onset of clinical effect occurs within 30–60 minutes for antihistaminic effects. For sedative effects, onset is 15–30 minutes. Intravenous: Onset within 5–10 minutes.
Duration of Action	Duration of antihistaminic effect is 4–6 hours; sedative effects last 6–8 hours. Clinical duration may be shorter in children and longer in elderly due to altered clearance.

Classification & Brands

Dosing & administration

Hydroxyzine pamoate (Orgatrax) 25-100 mg orally every 6-8 hours as needed; maximum 600 mg/day.

Dosage form	INJECTABLE
Renal impairment	For GFR <50 mL/min: administer 25 mg orally every 12 hours; monitor for excessive sedation.
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh B or C: initiate at 25 mg every 12 hours and titrate cautiously due to reduced clearance.
Pediatric use	Children ≥6 years: 0.5-1 mg/kg orally every 6-8 hours; maximum 50 mg/day. Children <6 years: 0.5 mg/kg orally every 6-8 hours; maximum 25 mg/day.
Geriatric use	Initiate at 25 mg orally every 8 hours; increase slowly due to increased risk of anticholinergic effects, sedation, and falls.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ORGATRAX (ORGATRAX).

Breastfeeding	Excreted in breast milk; M/P ratio not established. Potential for serious adverse reactions in nursing infants (e.g., renal toxicity, hypotonia). Decision to discontinue nursing or drug based on importance of drug to mother.
Teratogenic Risk	FDA Pregnancy Category D (based on animal studies and limited human data). First trimester: increased risk of major malformations (cardiac, CNS), spontaneous abortion. Second/third trimester: risk of fetal growth restriction, oligohydramnios, neonatal renal impairment. Avoid in pregnancy unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warning.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Concomitant use with pimozide, ergot alkaloids, or HMG-CoA reductase inhibitors (simvastatin, lovastatin).","Hypersensitivity to letermovir or any component of the formulation."]