DEMI-REGROTON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DEMI-REGROTON (DEMI-REGROTON).
DEMI-REGROTON is a fixed-dose combination of chlorothiazide (a thiazide diuretic) and reserpine (a Rauwolfia alkaloid). Chlorothiazide inhibits the Na+-Cl- symporter in the distal convoluted tubule, reducing sodium and water reabsorption. Reserpine depletes catecholamines (norepinephrine, dopamine, serotonin) from central and peripheral nerve endings by inhibiting vesicular monoamine transporter 2 (VMAT2), leading to reduced sympathetic outflow and vasodilation.
| Metabolism | Chlorothiazide: Not extensively metabolized; excreted unchanged in urine. Reserpine: Extensively metabolized in the liver via hydrolysis and glucuronidation; active metabolites. |
| Excretion | Renal: 70% as unchanged drug; biliary/fecal: 30% as metabolites |
| Half-life | Terminal elimination half-life is 40-60 hours (mean 48 h), allowing once-daily dosing; steady state reached in 5-7 days |
| Protein binding | 90% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 3-5 L/kg, indicating extensive extravascular distribution |
| Bioavailability | Oral: 65-75% due to first-pass metabolism |
| Onset of Action | Oral: 2-4 hours for antihypertensive effect; peak effect at 6-12 hours |
| Duration of Action | Antihypertensive effect persists for 24 hours after a single oral dose; maximal effect after 1-2 weeks of continuous therapy |
One tablet orally once daily, each tablet containing 25 mg chlorthalidone and 0.125 mg reserpine.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if GFR <30 mL/min. For GFR 30-60 mL/min, reduce dose to half tablet daily and monitor electrolytes. No adjustment needed if GFR >60 mL/min. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For Child-Pugh class B, use half the initial dose and titrate cautiously. No adjustment for Child-Pugh class A. |
| Pediatric use | Not recommended for pediatric use due to safety and efficacy data lacking. No established pediatric dosing guidelines. |
| Geriatric use | Initiate at half tablet (12.5 mg chlorthalidone/0.0625 mg reserpine) daily. Monitor for orthostatic hypotension, electrolyte imbalance, and CNS depression. Titrate slowly based on response and tolerability. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DEMI-REGROTON (DEMI-REGROTON).
| Breastfeeding | Excreted in breast milk in low amounts; M/P ratio not established. Potential for adverse effects in nursing infant such as hypotension. Use caution; consider alternative agent. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: potential risk of neural tube defects and cardiovascular anomalies based on animal studies; human data limited. Second and third trimesters: risk of fetal growth restriction, oligohydramnios, and neonatal hypotension due to renin-angiotensin system interference. Avoid in pregnancy unless no alternative. |
■ FDA Black Box Warning
Reserpine: Risk of mental depression and suicidal tendencies. Treatment should be discontinued at the first sign of depression.
| Serious Effects |
Hypersensitivity to chlorothiazide, reserpine, or sulfonamides; anuria; history of depression (especially with suicidal tendencies); active peptic ulcer; ulcerative colitis; concurrent electroconvulsive therapy (ECT).
| Precautions | Hypotension, electrolyte imbalance (especially hypokalemia), depression (with reserpine), peptic ulcer disease (reserpine may increase gastric acid secretion), and sensitivity reactions (chlorothiazide, sulfonamide derivative). |
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| Fetal Monitoring |
| Monitor maternal blood pressure and renal function. Perform serial fetal ultrasound for growth, amniotic fluid volume, and fetal well-being. Monitor neonatal blood pressure and renal function after delivery. |
| Fertility Effects | Potential reversible impairment of male and female fertility based on animal studies; clinical significance unknown. |