EUTRON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EUTRON (EUTRON).
EUTRON is a combination of hydrochlorothiazide (thiazide diuretic) and pargyline (monoamine oxidase inhibitor, MAOI). Hydrochlorothiazide inhibits sodium reabsorption in distal convoluted tubule, reducing plasma volume. Pargyline inhibits MAO, increasing catecholamine levels centrally, leading to antihypertensive effect.
| Metabolism | Hydrochlorothiazide: primarily excreted unchanged in urine. Pargyline: metabolized via MAO (its target) and other pathways; metabolites excreted renally. |
| Excretion | Renal excretion accounts for approximately 90% of elimination, with 70% as unchanged drug and 20% as metabolites. Biliary/fecal excretion accounts for the remaining 10%. |
| Half-life | Terminal elimination half-life is 12-15 hours in patients with normal renal function. In end-stage renal disease (ESRD), half-life may extend to 24-30 hours, requiring dose adjustment. |
| Protein binding | Approximately 95% bound to albumin. |
| Volume of Distribution | 0.3 L/kg, indicating distribution primarily in extracellular fluid. Higher Vd in heart failure (0.5 L/kg) due to increased tissue perfusion. |
| Bioavailability | Oral: 60-70% due to first-pass metabolism; significantly reduced by food (decrease by 30%). |
| Onset of Action | Oral: 1-2 hours; Intravenous: 5-15 minutes. |
| Duration of Action | Duration of antihypertensive effect is 12-24 hours with oral dosing, supporting once-daily administration. Maximal effect may take 2-4 weeks. |
Oral: 5 mg/2.5 mg (amiodipine/valsartan) once daily; maximum dose 10 mg/320 mg once daily.
| Dosage form | TABLET |
| Renal impairment | eGFR ≥30 mL/min/1.73 m²: No adjustment. eGFR <30 mL/min/1.73 m²: Contraindicated due to valsartan component. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Use caution; maximum amiodipine dose 5 mg daily. Child-Pugh C: Not recommended. |
| Pediatric use | Not established for patients <18 years. |
| Geriatric use | Initiate at lowest dose (5 mg/2.5 mg once daily) due to increased sensitivity and reduced hepatic/renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EUTRON (EUTRON).
| Breastfeeding | Excreted in breast milk; M/P ratio 0.05-0.2. Contraindicated due to risk of neonatal toxicity (myelosuppression, carcinogenesis). |
| Teratogenic Risk | First trimester: Fetal malformations (neural tube defects, cardiovascular anomalies) due to folate antagonism; contraindicated. Second trimester: Increased risk of growth restriction and oligohydramnios. Third trimester: Neonatal adverse effects including bone marrow suppression and pulmonary hypertension. |
| Fetal Monitoring |
■ FDA Black Box Warning
This drug is no longer approved by FDA. Historical black box warning: Pargyline may cause hypertensive crisis when used with certain foods (tyramine-rich) or drugs.
| Serious Effects |
["Concurrent use of other MAOIs or selective serotonin reuptake inhibitors (SSRIs)","Pheochromocytoma","Hypersensitivity to sulfonamides (cross-reactivity with thiazide)","Anuria"]
| Precautions | ["Hypertensive crisis due to dietary tyramine or sympathomimetic drugs","Orthostatic hypotension","Electrolyte imbalance from thiazide","Renal impairment","Hepatic encephalopathy"] |
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| Maternal complete blood count, liver function, renal function, uric acid levels; fetal ultrasound for anomalies and growth, amniotic fluid volume assessment. |
| Fertility Effects | Reversible impairment of spermatogenesis and oogenesis; may cause menstrual irregularities and oligospermia. |