NADOLOL AND BENDROFLUMETHIAZIDE
Clinical safety rating: caution
Other drugs that lower heart rate or blood pressure can have additive effects Abrupt withdrawal may exacerbate angina pectoris or cause myocardial infarction.
Nadolol is a nonselective beta-adrenergic receptor antagonist that blocks beta1 and beta2 receptors, reducing heart rate, myocardial contractility, and blood pressure. Bendroflumethiazide is a thiazide diuretic that inhibits the sodium-chloride symporter in the distal convoluted tubule, increasing excretion of sodium and water and reducing plasma volume.
| Metabolism | Nadolol is not significantly metabolized and is excreted unchanged in urine. Bendroflumethiazide is primarily metabolized in the liver via cytochrome P450 enzymes, though specific isoforms are not well defined. |
| Excretion | Nadolol: ~70% renal unchanged, ≤5% fecal. Bendroflumethiazide: ~30% renal unchanged, ~70% renal as metabolites; minimal biliary. |
| Half-life | Nadolol: 14–24 h (mean 20 h); allows once-daily dosing. Bendroflumethiazide: 3–4 h (terminal); clinical duration longer due to prolonged action on distal tubule. |
| Protein binding | Nadolol: ~30% (albumin). Bendroflumethiazide: ~94% (albumin). |
| Volume of Distribution | Nadolol: ~2 L/kg; large due to low lipophilicity and tissue binding. Bendroflumethiazide: ~1 L/kg; distribution into tissues, minimal CNS. |
| Bioavailability | Nadolol: ~30–40% oral; food decreases absorption. Bendroflumethiazide: ~85% oral; food may slow absorption. |
| Onset of Action | Nadolol: 1–2 h oral; Bendroflumethiazide: 2–4 h oral (diuresis); full antihypertensive effect 1–2 weeks. |
| Duration of Action | Nadolol: 24+ h; permits once-daily. Bendroflumethiazide: diuresis 6–12 h; antihypertensive 24 h. |
Nadolol 40–80 mg orally once daily; bendroflumethiazide 2.5–5 mg orally once daily. Dose titration based on blood pressure response.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if CrCl <30 mL/min. For CrCl 30–50 mL/min: extend dosing interval to every 36–48 hours. CrCl >50 mL/min: no adjustment. |
| Liver impairment | No specific guidelines; use with caution in severe hepatic impairment due to risk of hypoglycemia and hypotension. |
| Pediatric use | Not recommended for pediatric use due to lack of safety and efficacy data. |
| Geriatric use | Initiate at low end of dosing (nadolol 40 mg, bendroflumethiazide 2.5 mg daily); monitor renal function and electrolytes; adjust for renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other drugs that lower heart rate or blood pressure can have additive effects Abrupt withdrawal may exacerbate angina pectoris or cause myocardial infarction.
| FDA category | Animal |
| Breastfeeding | Nadolol is excreted in breast milk (M/P ratio ~0.9 - 2.0); potential for infant bradycardia, hypotension. Bendroflumethiazide is present in minimal amounts but may suppress lactation. Use caution, monitor infant for adverse effects. |
| Teratogenic Risk | First trimester: Possible fetal bradycardia and hypotension; limited human data show no consistent major malformations. Second/third trimester: Risk of fetal growth restriction, neonatal hypoglycemia, bradycardia, and hypotension. Bendroflumethiazide may cause fetal electrolyte disturbances, thrombocytopenia. |
■ FDA Black Box Warning
None
| Common Effects | angina |
| Serious Effects |
["Bronchial asthma","Severe bradycardia or heart block greater than first degree","Cardiogenic shock","Uncompensated heart failure","Anuria or severe renal impairment (with thiazide diuretic)","Hypersensitivity to nadolol, bendroflumethiazide, or sulfonamide-derived drugs"]
| Precautions | ["Abrupt discontinuation may exacerbate angina or precipitate myocardial infarction in patients with coronary artery disease","May mask signs of hyperthyroidism or hypoglycemia","May precipitate bronchospasm in patients with asthma or COPD","Monitor renal function and electrolytes due to thiazide component","May cause hyperglycemia, hyperuricemia, or hypokalemia"] |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, electrolytes, and renal function. Fetal growth ultrasound, fetal heart rate monitoring, and neonatal assessment for bradycardia, hypoglycemia, and electrolyte imbalance. |
| Fertility Effects | Limited data; nadolol may impair fertility due to beta-blockade effects on reproductive function. Bendroflumethiazide may cause electrolyte disturbances affecting fertility. No specific human studies. |