nadolol/bendroflumethiazide (Corzide)
Classes: Thiazide Combos; Beta-Blocker/Thiazide Diuretic Combos
Dosing and uses of Corzide (nadolol/bendroflumethiazide)
Adult dosage forms and strengths
nadolol/bendroflumethiazide
tablet
- 40mg/5mg
- 80mg/5mg
Hypertension
Not indicated for initial therapy
If the fixed dose combination represents the dose appropriate to the individual patient's needs, it may be more convenient than the separate components
Initial dose: Nadolol 40 mg/bendroflumethiazide 5 mg PO qDay
Increase to Nadolol 80 mg/bendroflumethiazide 5 mg PO qDay if needed
Bendroflumethiazide 5 mg in combination product is 30% more bioavailable than that of 5 mg in single entity tablets
When necessary, another antihypertensive agent may be added gradually beginning with 50 percent of the usual recommended starting dose to avoid an excessive fall in blood pressure
Renal Impairment
Use caution in dosing/titrating patients with renal dysfunction
Cumulative effects of thiazides may develop with impaired renal function
CrCl >50 mL/min/1.73 m²: Administer qDay
CrCl 31-50 mL/min/1.73 m²: Administer q24-36 hr
CrCl 10-30 mL/min/1.73 m²: Administer q24-48 hr
CrCl <10 mL/min/1.73 m²: Administer q40-60 hr
Administration
Combination may be substituted for the titrated individual components, though conversion from 5 mg bendroflumethiazide in single entity tablets to combination product represents a 30 percent increase in dose of bendroflumethiazide
Withdraw gradually over a period of about 2 weeks
Pediatric dosage forms and strengths
<18 years: Safety/efficacy not established
Geriatric dosage forms and strengths
Dose reduction may be necessary depending on patient's renal function
Corzide (nadolol/bendroflumethiazide) adverse (side) effects
No adverse effects specific to the combination have been observed; adverse effects limited to those previously reported with nadolol and bendroflumethiazide
Frequency not defined
NadoloL
- Abdominal discomfort
- Constipation
- Diarrhea
- CHF
- Nausea
- Cough
- Nasal congestion
- Drowsiness
- Insomnia
- Palpitaion
- Decreased sexual ability
- Bradycardia
- Dizziness
- Fatigue
- Hypotension
Bendroflumethiazide
- Hypotension
- Anorexia, epigastric distress
- Phototoxicity
- Hypercalcemia
- Hyperuricemia
- Hyperlipidemia
- Hypercholesterolemia
- Hypochloremia
- Hypokalemia (common)
- Hypomagnesemia
- Hyponatremia
- Glucose intolerance
Warnings
Black box warnings
Hypersensitivity to catecholamines has been observed during withdrawaL
Exacerbation of angina and, in some cases, myocardial infarction occurrence after abrupt discontinuation
When discontinuing chronically administered beta-blockers (particularly with ischemic heart disease) gradually reduce dose over 1-2 wk and carefully monitor
If angina markedly worsens or acute coronary insufficiency develops, reinstate beta-blocker administration promptly, at least temporarily (in addition to other measures appropriate for unstable angina)
Warn patients against interruption or discontinuation of beta-blocker without physician advice
Because coronary artery disease is common and may be unrecognized, slowly discontinue beta-blocker therapy, even in patients treated only for hypertension
Contraindications
Anuria
Cardiogenic shock
Heart block 2°/3°
Hypersensitivity to either component or sulfonamides
Overt cardiac failure
Sinus bradycardia
Uncompensated cardiac failure
Asthma
Cautions
Anesthesia/surgery (myocardial depression); chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery, however the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures
Bronchospastic disease
Cerebrovascular insufficiency
CHF, beta blockade carries the potential hazard of further depressing myocardial contractility and precipitating more severe failure
DM, fluid or electrolyte imbalance, hyperuricemia or gout, hypotension, SLe
Liver disease
May aggravate digitalis toxicity
Peripheral vascular disease
Renal impairment
Risk of male sexual dysfunction
Sensitivity reactions may occur with or without history of allergy or asthma
May interfere with phenolsulfonphthalein test; may produce false negatives in phentolamine and tyramine tests
Avoid abrupt withdrawaL
Pregnancy and lactation
Pregnancy category : C
Lactation: excreted in breast milk, use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Corzide (nadolol/bendroflumethiazide)
Mechanism of action
Nadolol/bendroflumethiazide is a fixed-combination tablet that combines a Beta adrenergic receptor blocker nadolol and a diuretic, bendroflumethiazide
Nadolol blocks beta-1 & beta-2 adrenergic receptors
Bendroflumethiazide, a thiazide diuretic, inhibits Na+ reabsorption in distal renal tubules resulting in increased excrertion of Na+ & water, also K+ & H+ ions
Pharmacokinetics
NadoloL
- Half-Life: 10-24 hr; prolonged in renal impairment
- Bioavailability: 30-40%
- Onset: 3-4 hr
- Duration: 17-24 hr
- Vd: 1.9 L/kg
- Protein binding: 30%
- Excretion: Urine
- Peak plasma time: 2-4 hr
Bendroflumethiazide
- Half-Life: 3-3.9 hr
- Bioavailability: In combination with nadolol increases 30% compared to bendroflumethiazide alone
- Onset: 2 hr (diuresis); 3-4 hr (hypertension)
- Duration: 18-24 hr (diuresis); 7 days (hypertension)
- Peak Plasma Time: 4 hr
- Excretion: Urine
- Dialyzable: No (HD)