Adult Dosing

Hypertension

• 1 tablet PO bid
• Max: 160 mg/50 mg (propranolol/hydrochlorothiazide)/day

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Management of hypertension

• Hypersensitivity to any of the ingredients of the product
• Hypersensitivity to sulfonamide-derived drugs
• Cardiogenic shock
• Sinus bradycardia and greater than first-degree block
• Bronchial asthma
• Congestive heart failure
• Anuric patients
• Sick sinus syndrome w/o pacemaker
• Atrioventricular block, 2nd or 3rd degree

• 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
• Patients with angina pectoris should be cautioned against interruption or cessation of therapy without the physician's advice
• If exacerbation of angina occurs on interruption of therapy, re-institute propranolol therapy and use other measures appropriate for the management of unstable angina pectoris. Because coronary artery disease may be unrecognized, it is advisable to follow the above recommendations in patients considered at risk of having occult atherosclerotic heart disease receiving propranolol for other indications

Renal Dose Adjustment

• Renal impairment: Dose adjustments not defined; use with caution

Hepatic Dose Adjustment

• Hepatic impairment: Dose adjustments not defined; use with caution

See Supplemental Patient Information

• Carries increased risk of further depressing myocardial contractility and precipitating cardiac failure. In patients receiving digitalis, propranolol may reduce the positive inotropic action of digitalis
• During propranolol therapy, continued depression of the myocardium have been observed over a period of time which leads to cardiac failure
• During the appearance of first sign/symptom of cardiac failure, fully digitalize the patients and/or give additional diuretic and monitor the response closely. Withdraw propranolol gradually, if cardiac failure continues despite sufficient digitalization and diuretic therapy. If tachyarrhythmia is controlled, patient should maintain the combination therapy and be closely monitored until threat of cardiac failure is over
• 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 [US Black Box Warning]
• In patients with nonallergic bronchospasm, beta-blockers should be used with caution because it may block bronchodilation produced by endogenous and exogenous catecholamine stimulation of beta receptors
• Withdrawing beta-blockers prior to major surgery is controversial; there may be an increased risk of general anesthesia and surgical procedures because of the impaired ability of the heart to respond to reflex adrenergic stimuli
• Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, may occur following propranolol and thiazide therapy
• Thiazides may potentiate the action of other antihypertensive drugs
• Thiazides can cause an idiosyncratic reaction resulting in acute transient myopia and acute angle-closure glaucoma; untreated acute angle-closure glaucoma may cause permanent vision loss. Discontinue therapy as rapidly as possible and institute prompt medical or surgical treatment if intraocular pressure remains uncontrolled
• Propranolol may prevent the appearance of certain premonitory signs and symptoms (eg, pulse rate and BP changes) of acute hypoglycemia in labile insulin-dependent diabetes
• Hypoglycemic attack may be accompanied by a precipitous elevation of blood pressure in patients on propranolol
• Propranolol may mask a few clinical signs (eg, tachycardia) of developing or continuing hyperthyroidism. Abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm. Propranolol may change thyroid function tests, increasing T4 and reverse T3, and decreasing T3
• In several reported cases, tachycardia was replaced by severe bradycardia requiring a demand pacemaker
• Cutaneous skin reactions have been reported with the use of propranolol
• Thiazides may precipitate azotemia in renal disease patients
• Exacerbation or activation of systemic lupus erythematosus has been reported with the use of thiazides
• Patients receiving thiazide should be observed for clinical signs of fluid or electrolyte imbalance
• Hypokalemia may develop, especially with brisk diuresis, or due to severe cirrhosis
• Interference with adequate oral electrolyte intake will contribute to hypokalemia. Hypokalemia can sensitize or exaggerate the response of the heart to the toxic effects of digitalis
• Dilutional hyponatremia may occur in edematous patients in hot weather, appropriate therapy must be used in such patients
• Hyperuricemia may occur or frank gout may be precipitated by thiazide therapy
• Dose adjustment of insulin or oral hypoglycemic agents required in diabetic patient, hyperglycemia may occur with thiazide diuretic
• Postsympathectomy may enhance antihypertensive effects of thiazides
• Discontinue or withhold diuretic therapy if progressive renal impairment becomes evident
• Prolonged thiazide therapy may cause pathologic changes in the parathyroid gland with hypercalcemia and hypophosphatemia

Cautions: Use cautiously in:

• History of allergy or bronchial asthma
• Renal impairment
• Hepatic impairment or progressive liver disease
• Bronchospastic lung disease
• Peripheral vascular disease
• Major surgery
• Diabetes mellitus
• Thyroid disorder
• Wolff-Parkinson-White syndrome
• Elderly patients
• Volume depletion
• Electrolyte abnormalities
• Gout
• Post-sympathectomy
• Arrhythmias

Supplemental Patient Information

• Advise patients that beta-adrenoreceptor blockade can cause reduced intraocular pressure
• Caution patients that propranolol/hydrochlorothiazide therapy may interfere with glaucoma screening test
• Caution patients that withdrawal may cause return of increased intraocular pressure

Pregnancy Category:C

Breastfeeding: Probably safe; as low levels of propranolol are excreted in breast milk, amounts ingested by the infants are too small to cause any adverse effects in breastfed infants. During lactation, hydrochlorothiazide at a dose of 50 mg daily or less is acceptable. Intense diuresis with large doses may decrease breast milk production. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 22 February 2011). As per the manufacturer's data, propranolol and hydrochlorothiazide are excreted in breast milk. If the use of drug is deemed essential, the patient should stop nursing.

• CV: CHF, hypotension, intensification of AV block, severe bradycardia, arterial insufficiency (Raynaud phenomenon), orthostatic hypotension, arrhythmias
• CNS: Mental depression progressing to catatonia, insomnia, lassitude, short-term memory loss, emotional lability, slightly clouded sensorium, decreased performance on neuropsychometrics, restlessness, hallucinations, vivid dreams, lightheadedness, dizziness, vertigo, headache, xanthopsia, paresthesias
• EENT: Visual disturbances, transient blurred vision
• GI: Mesenteric arterial thrombosis, ischemic colitis, nausea, vomiting, epigastric distress, abdominal cramping, diarrhea, constipation, pancreatitis, jaundice, sialadenitis, anorexia, gastric irritation
• METABOLIC: Severe hypokalemia, electrolyte imbalance, metabolic alkalosis, hyperglycemia, hyperlipidemia
• GU: Renal failure, glycosuria, male impotence
• HYPERSENSITIVITY: Anaphylactic/anaphylactoid reactions, laryngospasm, respiratory distress, pharyngitis, necrotizing angiitis, fever combined with aching and sore throat, erythematous rash, photosensitivity
• RESP: Bronchospasm
• IMMU: Systemic lupus erythematosus
• HEMA: Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenic purpura, aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia, hyperuricemia
• DERM: Stevens-Johnson Syndrome, toxic epidermal necrolysis, exfoliative dermatitis, erythema multiforme, urticaria, alopecia
• MUSC: Muscle spasms/cramps
• MISC: Weakness, fatigue

Propranolol

• Beta-adrenergic blockers; nonselectively blocks beta-adrenergic receptors, causes reduction in heart rate, cardiac output, myocardial contractility, systolic and diastolic blood pressure, and increases systolic ejection time and cardiac volume
• Metabolized by liver, CYP450: 2D6, 1A2 enzyme
• Excreted in urine (<1% unchanged)
• Half-life: 4 hrs

Hydrochlorothiazide

• Thiazide diuretic; increases chloride, sodium, and water excretion by interfering with transport of sodium ions across renal tubular epithelium
• Not metabolized
• Excreted in urine
• Half-life: 5.6-14.8 hrs

US Trade Name(s)

• Inderide-40/25

US Availability

propranolol/hydrochlorothiazide (generic)

• TABS: 40 mg/25 mg
• TABS: 80 mg/25 mg

Inderide-40/25 (propranolol/hydrochlorothiazide)

• TABS: 40 mg/25 mg

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Cardiovascular

Antihypertensive Combinations

• HCTZ 25 MG / propranolol hydrochloride 40 MG Oral Tablet (Actavis Elizabeth LLC)
• HCTZ 25 MG / propranolol hydrochloride 40 MG Oral Tablet (Mylan Pharmaceuticals Inc.)
• HCTZ 25 MG / propranolol hydrochloride 80 MG Oral Tablet (Actavis Elizabeth LLC)
• HCTZ 25 MG / propranolol hydrochloride 80 MG Oral Tablet (Mylan Pharmaceuticals Inc.)
• Inderide 40/25 Oral Tablet (Wyeth Pharmaceuticals, Inc.)
• Inderide 80/25 Oral Tablet (Wyeth Pharmaceuticals, Inc.)