nadolol/bendroflumethiazide (Corzide)

Dosing and uses of Corzide (nadolol/bendroflumethiazide)

• Adult
• Pediatric
• Geriatric

 

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)