REGROTON
Clinical safety rating
cautionComprehensive 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 |
| Molecular Weight | 531.4 |
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 | Avoid. Contraindicated due to teratogenic effects (thiazide diuretics may cause fetal jaundice and thrombocytopenia; reserpine increases risk of fetal bradycardia, hypothermia, and nasal congestion). |
| 2nd trimester | Avoid. May cause fetal electrolyte disturbances and adverse effects on placental perfusion. |
| 3rd trimester | Avoid. Associated with neonatal thrombocytopenia, jaundice, and electrolyte imbalances. |
Clinical note
Comprehensive clinical and safety monograph for REGROTON (REGROTON).
| Placental transfer | Both agents cross the placenta; reserpine accumulates in fetal tissues. Chlorthalidone is known to cross the placental barrier and may cause fetal electrolyte abnormalities. |
| Breastfeeding | Both reserpine and chlorthalidone (components of REGROTON) are excreted into breast milk. Reserpine may cause extrapyramidal symptoms and galactorrhea in nursing infants, while thiazides may suppress lactation. Use not recommended due to risk of neonatal electrolyte disturbances and drowsiness. |
| Lactation Rating | L4 (Possibly Hazardous) |
| 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. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to reserpine, chlorthalidone, or sulfonamide-derived drugsHistory of depression, especially with suicidal tendencies (reserpine component)Active peptic ulcer diseaseUlcerative colitisElectroconvulsive therapy (ECT)Severe renal impairment (creatinine clearance <30 mL/min or anuria)Severe hepatic impairmentHypokalemia refractory to treatmentPregnancy
| 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. |
| Food/Dietary | Avoid high-potassium foods and salt substitutes (e.g., bananas, oranges, spinach, potassium-containing salt substitutes) due to risk of hyperkalemia with chlorthalidone. Limit alcohol intake. Maintain adequate hydration but avoid excessive fluid intake. Grapefruit juice may increase atenolol absorption; limit intake. Take with food to reduce GI upset. |
| Clinical Pearls | REGROTON is a fixed-dose combination of chlorthalidone (a thiazide-like diuretic) and atenolol (a cardioselective beta-blocker). Monitor for hypokalemia, hyperuricemia, and glucose intolerance from chlorthalidone. Atenolol may mask tachycardia in hypoglycemia and cause bradycardia; avoid abrupt discontinuation. Dosing adjustment needed in renal impairment (CrCl <30 mL/min contraindicated). Caution in COPD/asthma bronchospasm, peripheral vascular disease, and heart failure. |
| Patient Advice | Take exactly as prescribed, usually once daily, preferably in the morning to avoid nocturia. · Do not stop taking abruptly; sudden discontinuation may cause chest pain or palpitations. · Report signs of electrolyte imbalance: muscle cramps, weakness, irregular heartbeat, or excessive thirst. · Check blood pressure and pulse regularly; keep a log. · Avoid alcohol, which can increase blood pressure lowering effects and cause dizziness. · May cause dizziness or lightheadedness; rise slowly from sitting or lying positions. · Inform your doctor if you develop shortness of breath, wheezing, swelling, or unusual weight gain. · This drug may increase blood sugar; monitor glucose if diabetic. · Use sunscreen and protective clothing; medication can increase sun sensitivity. |
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