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Propranolol Hydrochloride / Hydrochlorothiazide ( HCTZ )

Pronunciation: pro-PRAN-oh-lahl HIGH-droe-KLOR-ide/high-droe-klor-THIGH-uh-zide
Class: Antihypertensive combination

Trade Names

Propranolol Hydrochloride/Hydrochlorothiazide
- Tablets 40 mg propranolol/25 mg hydrochlorothiazide
- Tablets 80 mg propranolol/25 mg hydrochlorothiazide

Pharmacology

Propranolol

Blocks beta receptors, primarily affecting the CV system (decreases heart rate, cardiac contractility, and BP) and lungs (promotes bronchospasm).

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Hydrochlorothiazide (HCTZ)

Increases chloride, sodium, and water excretion by interfering with transport of sodium ions across renal tubular epithelium.

Indications and Usage

Management of hypertension.

Contraindications

Cardiogenic shock; sinus bradycardia and greater than first-degree block; bronchial asthma; CHF (unless failure is secondary to a tachyarrhythmia treatable with propranolol); anuria; hypersensitivity to sulfonamide-derived drugs or any component of this product.

Dosage and Administration

The fixed combination is not indicated for initial therapy. The combination may be substituted for the titrated components.

Adults

PO HCTZ can be given at 12.5 to 50 mg/day when used alone. The initial propranolol dose is 80 mg/day and may be increased gradually until optimal BP control is achieved. The usual effective dose when used alone is 160 to 480 mg/day. One propranolol 80 mg/HCTZ 25 mg tablet twice daily can be used to administer up to 160 mg propranolol and 50 mg HCTZ. For propranolol doses greater than 160 mg, the combination products are inappropriate because their use would lead to excessive doses of HCTZ.

General Advice

  • Administer last dose late in the afternoon to reduce nighttime urination.
  • Administer without regard to meals. Administer with food if GI upset occurs.

Storage/Stability

Store at controlled room temperature (less than 77°F).

Drug Interactions

Propranolol Aluminum hydroxide

May decrease intestinal absorption of propranolol.

Antipyrine, lidocaine

May reduce the Cl of propranolol.

Calcium-channel blocking agent (eg, verapamil)

May have additive of synergistic effects with propranolol, depressing myocardial contractility or atrioventricular conduction.

Catecholamine-depleting drugs (eg, reserpine)

May produce excessive reduction of resting sympathetic nervous activity, which may result in hypotension, marked bradycardia, vertigo, syncopal attacks, or orthostatic hypotension.

Chlorpromazine

Increased plasma concentrations of both chlorpromazine and propranolol.

Cimetidine

May decrease the metabolism of propranolol, delaying elimination and increasing the blood level.

Ethanol

May slow the rate of propranolol absorption.

Haloperidol

Hypotension and cardiac arrest have been reported with concurrent use of propranolol.

Phenobarbital, phenytoin, rifampin

May increase the rate of propranolol elimination.

Theophylline

Plasma levels may be increased by propranolol; in addition, propranolol may antagonize the effect of theophylline.

Thyroxine

May result in lower T 3 concentrations when used concomitantly with propranolol.

HCTZ Alcohol, barbiturates, narcotics

Increased risk of orthostatic hypotension.

Antidiabetic agents (oral agents and insulin)

Dosage adjustment of antidiabetic agent may be necessary.

Antihypertensive agent

Additive or potentiation of effects.

Cholestyramine, colestipol resins

Impaired absorption of HCTZ.

Corticosteroids, ACTH

Increased electrolyte depletion, increasing the risk of hypokalemia.

Lithium

Renal Cl of lithium may be reduced, increasing the risk of lithium toxicity.

Nondepolarizing skeletal muscle relaxants (eg, tubocurarine)

Increased effect of the muscle relaxant.

NSAIDs

The diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing, and thiazide diuretics may be reduced.

Pressor amines (eg, norepinephrine)

Decreased responsiveness to the pressor amine.

Laboratory Test Interactions

May decrease serum protein-bound iodine levels without signs of thyroid disturbances. May cause diagnostic interference of serum electrolyte levels, blood and urine glucose levels, serum bilirubin levels, and serum uric acid levels.

Adverse Reactions

Cardiovascular

HCTZ

Orthostatic hypotension.

Propranolol

CHF, hypotension, intensification of AV block, bradycardia, thrombocytopenia purpura, arterial insufficiency (usually of the Raynaud type), paresthesia of hands.

CNS

HCTZ

Dizziness, vertigo, headache, xanthopsia, paresthesias, weakness, restlessness.

Propranolol

Mental depression (progressing to catatonia); mental depression (manifested by insomnia, lassitude, weakness, fatigue); acute syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, decreased performance on neuropsychometrics; hallucinations; vivid dreams; lightheadedness; fatigue; lethargy.

Dermatologic

Propranolol

Alopecia, psoriaform rashes, oculomucocutaneous reactions (involving the skin, serous membranes, and conjunctivae).

EENT

HCTZ

Blurred vision.

Propranolol

Visual disturbances, dry eyes.

GI

HCTZ

Pancreatitis, sialadenitis, anorexia, nausea, vomiting, gastric irritation, cramping, diarrhea, constipation.

Propranolol

Mesenteric arterial thrombosis; ischemic colitis; nausea; vomiting; epigastric distress; abdominal cramping; diarrhea; constipation.

Genitourinary

Propranolol

Impotence.

Hematologic

HCTZ

Aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia.

Propranolol

Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenic purpura.

Hepatic

HCTZ

Jaundice (intrahepatic cholestatic).

Metabolic

HCTZ

Hypokalemia, hyperuricemia, hyponatremia, hyperglycemia, glucosuria.

Respiratory

Propranolol

Bronchospasm.

Miscellaneous

HCTZ

Hypersensitivity (including anaphylactic reactions, necrotizing angiitis, respiratory distress, fever, urticaria, rash, purpura, photosensitivity); muscle spasm.

Propranolol

Allergic reaction (including laryngospasm, respiratory distress, pharyngitis, agranulocytosis, fever, aching and sore throat, erythematous rash); systemic lupus erythematosus; Peyronie disease.

Precautions

Monitor

Blood sugar

Monitor blood sugar in diabetic patients when drug is started or dose is changed.


Pregnancy

Category C .

Lactation

Propranolol and HCTZ are secreted in breast milk.

Children

Safety and efficacy not established.

Elderly

Select dose with caution, reflecting greater frequency of decreased hepatic, renal, or cardiac function and comorbidity.

Renal Function

Use with caution; minor alterations of fluid and electrolyte balance may precipitate hepatic coma (HCTZ).

Hepatic Function

Use with caution; minor alterations of fluid and electrolyte balance may precipitate hepatic coma (HCTZ).

Anesthesia and major surgery

Withdrawing beta-blockers prior to major surgery is controversial; beta blockade impairs the heart's ability to respond to beta-adrenergically mediated reflex stimuli.

Angina pectoris

Exacerbation of angina and MI may occur following abrupt discontinuation of propranolol; therefore, discontinue propranolol by gradually reducing the dosage and carefully monitoring the patient.

Cardiac failure

Increased risk of further depressing myocardial contractility and precipitating cardiac failure. In patients receiving digitalis, propranolol may reduce the positive inotropic action of digitalis.

Diabetes and hypoglycemia

Propranolol may prevent the appearance of certain premonitory signs and symptoms (eg, pulse rate and BP changes) of acute hypoglycemia.

Electrolyte imbalance

Do not use in patients with hyponatremia, hypochloremic alkalosis, hypokalemia, or hypomagnesemia prior to correction of imbalance.

Hyperuricemia

May occur or frank gout may be precipitated by thiazide therapy.

Nonallergic bronchospasm (eg, chronic bronchitis, emphysema)

Use beta-blockers with caution because it may block bronchodilation produced by endogenous and exogenous catecholamine stimulation of beta receptors.

Systemic lupus erythematosus (HCTZ)

Exacerbation or activation may occur.

Thyrotoxicosis

Propranolol may mask certain clinical signs of hyperthyroidism (eg, tachycardia).

Wolff-Parkinson-White syndrome

In several reported cases, tachycardia was replaced by severe bradycardia requiring a demand pacemaker.

Overdosage

Symptoms

Bradycardia, cardiac failure, hypotension, bronchospasm, diuresis, lethargy, coma, depression of respiration and cardiac function, CNS depression, GI irritation and hypermotility, temporary elevated BUN.

Patient Information

  • Advise patient to take prescribed dose twice daily, without regard to meals, but to take with food if GI upset occurs.
  • Advise patient to take last dose late in the afternoon to reduce chances of nighttime urination.
  • Advise patient to try to take each dose at about the same time each day.
  • Inform patient that drug controls, but does not cure, hypertension and to continue taking drug as prescribed even when BP is not elevated.
  • Caution patient not to change the dose or stop taking unless advised by health care provider.
  • Advise patient that if medication needs to be discontinued, the dose will be slowly reduced and then stopped.
  • Instruct patient to continue taking other BP medications as prescribed by health care provider.
  • Instruct patient in BP and pulse measurement skills.
  • Advise patient to monitor and record BP and pulse at home and to inform health care provider if abnormal measurements are noted. Also, advise patient to take record of BP and pulse to each follow-up visit.
  • Instruct patient to lie or sit down if experiencing dizziness or lightheadedness when standing.
  • Caution patient that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to excessive fall in BP resulting in lightheadedness or fainting.
  • Instruct patient to notify health provider immediately if any of the following occur: dryness of mouth, thirst, weakness, lethargy, unexplained drowsiness or restlessness, persistent muscle pain or cramps, persistent nausea or vomiting, decreased urine production, rapid or slow heartbeat, depressed feeling.
  • Instruct diabetic patient to monitor blood glucose more frequently when drug is started or dose is changed and to inform health care provider of significant changes in readings.
  • Caution patient to avoid unnecessary exposure to UV light (sunlight, tanning booths) and to use sunscreen and wear protective clothing when exposed to UV light to avoid photosensitivity reaction.
  • Emphasize to hypertensive patient importance of other modalities on BP: weight control, regular exercise, smoking cessation, and moderate intake of alcohol and salt.
  • Instruct patient that beta-blockers can cause reduction of IOP and may interfere with glaucoma screening test.

Copyright © 2009 Wolters Kluwer Health.

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