TRIATEX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TRIATEX (TRIATEX).

How it works

TRIATEX (methotrexate) inhibits dihydrofolate reductase, blocking tetrahydrofolate synthesis and thereby interfering with DNA synthesis, repair, and cellular replication. It also has immunomodulatory and anti-inflammatory effects through adenosine-mediated pathways.

What the body does with it

Metabolism	Hepatic metabolism via aldehyde oxidase and possibly CYP450 enzymes; undergoes intracellular polyglutamation; primarily excreted renally via glomerular filtration and active tubular secretion.
Excretion	Primarily renal excretion (80-90% as unchanged drug via glomerular filtration and active tubular secretion) with 5-10% fecal elimination.
Half-life	Terminal elimination half-life is 8-12 hours (mean 10 hours) in adults with normal renal function; prolonged to 20-40 hours in moderate-severe renal impairment (CrCl <30 mL/min).
Protein binding	Approximately 85-90% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	0.8-1.2 L/kg, indicating extensive tissue distribution and penetration into extravascular spaces.
Bioavailability	Oral: 100% (complete absorption) with minimal first-pass metabolism; IM: 85-95% relative to IV.
Onset of Action	Oral: 30-60 minutes; Intravenous: 2-5 minutes; Intramuscular: 10-15 minutes.
Duration of Action	Oral: 8-12 hours; IV/IM: 4-8 hours, corresponding to therapeutic plasma levels above 1.5 mcg/mL.

Classification & Brands

Dosing & administration

Triatex (trianterene/hydrochlorothiazide) 37.5 mg/25 mg or 75 mg/50 mg orally once daily; may increase to maximum of 2 capsules daily.

Dosage form	CREAM
Renal impairment	Contraindicated if GFR < 30 mL/min. For GFR 30-50 mL/min: reduce dose to once daily of lowest strength and monitor potassium.
Liver impairment	Child-Pugh Class A: no adjustment needed. Child-Pugh Class B: reduce dose by 50%. Child-Pugh Class C: avoid use due to risk of hepatic encephalopathy.
Pediatric use	Not recommended for children under 18 years due to lack of safety data.
Geriatric use	Initiate at lowest dose (37.5 mg/25 mg once daily) to avoid excessive diuresis and electrolyte imbalance; monitor renal function and serum potassium closely.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for TRIATEX (TRIATEX).

Breastfeeding	Contraindicated in breastfeeding. Excreted into human milk; M/P ratio unknown. Potential for serious adverse effects in nursing infants including kernicterus and hemolytic anemia.
Teratogenic Risk	First trimester: Increased risk of neural tube defects and cardiovascular malformations due to folate antagonism. Second and third trimesters: Potential for oligohydramnios, fetal renal impairment, and premature closure of ductus arteriosus.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

WARNING: SEVERE TOXICITY, including fatal hepatotoxicity, pulmonary fibrosis, myelosuppression, and serious infections. Methotrexate should be used only in life-threatening or serious diseases. Patients must be closely monitored for bone marrow, liver, lung, and kidney toxicity. Methotrexate should not be used in pregnancy (category X) due to risk of fetal death or congenital anomalies.

Side Effect Profile

Serious Effects

Absolute Contraindications

Absolute: severe renal impairment (CrCl <10 mL/min), severe hepatic disease, alcoholism, pre-existing blood dyscrasias (e.g., bone marrow hypoplasia, leukopenia, thrombocytopenia), hypersensitivity to methotrexate, pregnancy (Category X), and lactation. Relative: concurrent NSAIDs (may increase toxicity), active infectious disease, compromised renal function, and hepatic fibrosis.

Clinical Precautions

Precautions

Hepatotoxicity (monitor liver function, avoid alcohol), pulmonary toxicity (acute or chronic interstitial pneumonitis), myelosuppression (monitor blood counts), renal toxicity (adjust dose in renal impairment), immunosuppression/infections, gastrointestinal toxicity, neurotoxicity, tumor lysis syndrome, photosensitivity, and vaccination risks.

Clinical Tips & Counseling

Drug interactions

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TRIATEX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TRIATEX (TRIATEX).

How it works

What the body does with it

Metabolism	Hepatic metabolism via aldehyde oxidase and possibly CYP450 enzymes; undergoes intracellular polyglutamation; primarily excreted renally via glomerular filtration and active tubular secretion.
Excretion	Primarily renal excretion (80-90% as unchanged drug via glomerular filtration and active tubular secretion) with 5-10% fecal elimination.
Half-life	Terminal elimination half-life is 8-12 hours (mean 10 hours) in adults with normal renal function; prolonged to 20-40 hours in moderate-severe renal impairment (CrCl <30 mL/min).
Protein binding	Approximately 85-90% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	0.8-1.2 L/kg, indicating extensive tissue distribution and penetration into extravascular spaces.
Bioavailability	Oral: 100% (complete absorption) with minimal first-pass metabolism; IM: 85-95% relative to IV.
Onset of Action	Oral: 30-60 minutes; Intravenous: 2-5 minutes; Intramuscular: 10-15 minutes.
Duration of Action	Oral: 8-12 hours; IV/IM: 4-8 hours, corresponding to therapeutic plasma levels above 1.5 mcg/mL.

Classification & Brands

Dosing & administration

Triatex (trianterene/hydrochlorothiazide) 37.5 mg/25 mg or 75 mg/50 mg orally once daily; may increase to maximum of 2 capsules daily.

Dosage form	CREAM
Renal impairment	Contraindicated if GFR < 30 mL/min. For GFR 30-50 mL/min: reduce dose to once daily of lowest strength and monitor potassium.
Liver impairment	Child-Pugh Class A: no adjustment needed. Child-Pugh Class B: reduce dose by 50%. Child-Pugh Class C: avoid use due to risk of hepatic encephalopathy.
Pediatric use	Not recommended for children under 18 years due to lack of safety data.
Geriatric use	Initiate at lowest dose (37.5 mg/25 mg once daily) to avoid excessive diuresis and electrolyte imbalance; monitor renal function and serum potassium closely.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for TRIATEX (TRIATEX).

Breastfeeding	Contraindicated in breastfeeding. Excreted into human milk; M/P ratio unknown. Potential for serious adverse effects in nursing infants including kernicterus and hemolytic anemia.
Teratogenic Risk	First trimester: Increased risk of neural tube defects and cardiovascular malformations due to folate antagonism. Second and third trimesters: Potential for oligohydramnios, fetal renal impairment, and premature closure of ductus arteriosus.
Fetal Monitoring