REGROTON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REGROTON (REGROTON).
Regroton is a combination of reserpine and chlorthalidone. Reserpine depletes catecholamines from peripheral sympathetic nerve endings by inhibiting vesicular monoamine transporter 2 (VMAT2), leading to vasodilation and reduced heart rate. Chlorthalidone is a thiazide-like diuretic that inhibits sodium and chloride reabsorption in the distal convoluted tubule, reducing plasma volume and cardiac output.
| Metabolism | Reserpine is extensively metabolized in the liver via hydrolysis and conjugation; chlorthalidone is metabolized minimally, mainly excreted unchanged in urine, with some hepatic conjugation. |
| Excretion | Renal: 70-80% (50% as unchanged drug, 20-30% as metabolites); Fecal: <5% |
| Half-life | Terminal elimination half-life: 9-11 hours (mean 10 hours); clinical context: supports once-daily dosing in hypertension, steady-state reached in 3-4 days |
| Protein binding | Reserpine: 96% bound to albumin and alpha-1-acid glycoprotein; Chlorthalidone: 75% bound to erythrocytes (carbonic anhydrase) and 75% to plasma proteins (albumin) |
| Volume of Distribution | Reserpine: 2.5-3.5 L/kg; Chlorthalidone: 3-4 L/kg; clinical meaning: extensive tissue distribution with prolonged effect due to reserpine's irreversible binding to adrenergic neurons |
| Bioavailability | Oral: reserpine 30-50%; chlorthalidone 64% |
| Onset of Action | Oral: antihypertensive effect within 2-3 hours |
| Duration of Action | Duration: 24 hours; clinical notes: effective for once-daily dosing; in chlorthalidone, duration may extend up to 48-72 hours but for Regroton (reserpine/chlorthalidone) the combination follows chlorthalidone's duration |
1 tablet (25 mg chlorthalidone / 50 mg metoprolol) orally once daily.
| Dosage form | TABLET |
| Renal impairment | GFR 30-60 mL/min: use with caution; GFR <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh Class A/B: reduce metoprolol dose by 50%; Class C: avoid use. |
| Pediatric use | Not recommended for use in pediatric patients. |
| Geriatric use | Initiate at half the standard dose (25 mg chlorthalidone/25 mg metoprolol) and titrate slowly due to increased risk of hypotension and electrolyte imbalance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REGROTON (REGROTON).
| Breastfeeding | Chlorthalidone and reserpine are excreted into breast milk. Chlorthalidone M/P ratio not established; reserpine M/P ratio approximately 0.5. Use with caution due to potential for adverse effects in the nursing infant, including electrolyte disturbances and cardiac effects. Generally not recommended during breastfeeding. |
| Teratogenic Risk | Pregnancy Category D. First trimester: increased risk of neural tube defects, cardiac anomalies, and oral clefts due to chlorthalidone; potential for fetal hypotension and oligohydramnios. Second and third trimesters: fetal hypotension, oligohydramnios, intrauterine growth restriction, and neonatal complications including electrolyte imbalances, thrombocytopenia, and jaundice. Avoid use in pregnancy, especially during second and third trimesters. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to reserpine, chlorthalidone, or sulfonamides (chlorthalidone is a sulfonamide).","Active peptic ulcer disease.","History of mental depression (especially with suicidal tendencies).","Anuria or severe renal impairment.","Electrolyte depletion (untreated hypokalemia, hypercalcemia)."]
| Precautions | ["May cause depression, particularly in patients with history of depression; discontinue if signs appear.","Electrolyte imbalance (hypokalemia, hyponatremia) due to chlorthalidone.","Bradycardia and orthostatic hypotension.","Use cautiously in patients with renal impairment, gout, or diabetes.","Possible increased risk of breast cancer with long-term reserpine use."] |
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| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes (especially potassium, sodium, chloride), renal function, and uric acid. Fetal monitoring includes ultrasound for growth, amniotic fluid volume (oligohydramnios risk), and fetal heart rate assessment. Monitor newborn for electrolyte imbalances, hypotension, and jaundice after delivery. |
| Fertility Effects | Reserpine may cause gynecomastia, menstrual irregularities, and decreased libido in women; in men, it may cause erectile dysfunction and decreased sperm motility. Chlorthalidone may have minimal direct effects on fertility; however, electrolyte disturbances could potentially affect reproductive function. |