Bisoprolol Fumarate / Hydrochlorothiazide	(bih-SO-pro-lahl FEW-mah-rate/high-droe-klor-oh-THIGH-uh-zide)
Trade Name(s):	Ziac   ·Tablets 6.25 mg hydrochlorothiazide/2.5?mg bisoprolol fumarate   ·Tablets 6.25 mg hydrochlorothiazide/5 mg bisoprolol fumarate   ·Tablets 6.25 mg hydrochlorothiazide/10 mg bisoprolol fumarate Indicates Canadian Trade Name.
Class:	Antihypertensive
Action:	Blocks beta receptors, primarily affecting CV system and lungs (bisoprolol); inhibits reabsorption of sodium and chloride in ascending loop of Henle and early distal tubules (hydrochlorothiazide).
Indications:	Management of hypertension.
Contraindications:	Cardiogenic shock; overt cardiac failure; second or third degree AV block; marked sinus bradycardia; anuria; hypersensitivity to either component of product or other sulfonamide derivatives.
Interactions:
	Bisoprolol
	Antiarrhythmic agents (eg, disopyramide), diphenylalkylamine calcium antagonists (eg, verapamil), benzothiazepine calcium antagonists (eg, diltiazem) Use with caution.
	Antihypertensives Actions of other antihypertensive agents may be potentiated.
	Beta-blockers Do not combine with other beta-blockers.
	Catecholamine-depleting agents (eg, guanethidine, reserpine) Sympathetic action may be considerably reduced.
	Clonidine If discontinuing clonidine after coadministration with bisoprolol/hydrochlorothiazide, discontinue bisoprolol/hydrochlorothiazide several days before withdrawal of clonidine.
	Hydrochlorothiazide
	Alcohol, barbiturates, narcotics Increased risk of orthostatic hypotension.
	Antidiabetic agents Dose adjustments in antidiabetic agent may be needed.
	Antihypertensives Actions of other antihypertensive agents may be potentiated.
	Cholestyramine, colestipol resins Absorption of hydrochlorothiazide may be impaired.
	Adrenocorticotropic hormone, corticosteroids Increased risk of electrolyte depletion (eg, hypokalemia).
	Pressor amines (eg, norepinephrine) Decreased response to pressor amine.
	Nondepolarizing skeletal muscle relaxants (eg, tubocurarine) Responsiveness to muscle relaxant may be increased.
	Lithium Plasma levels of lithium may be elevated, increasing the risk of toxicity.
	NSAIDs The antihypertensive, diuretic, and natriuretic effect of hydrochlorothiazide may be reduced.
Lab Test Interferences:	Serum levels of protein-bound iodine may be decreased without signs of thyroid dysfunction.
Adverse Reactions:
	cardiovascular: Bradycardia; arrhythmia; peripheral ischemia; chest pain; palpitations and rhythm disturbances, cold extremities, claudication, hypotension; orthostatic hypotension, chest pain, CHF (bisoprolol); orthostatic hypotension (hydrochlorothiazide).
	cns: Fatigue; dizziness; headache; insomnia; somnolence; loss of libido; impotence; unsteadiness, vertigo, syncope, paresthesia, hyperesthesia, sleep disturbances, vivid dreams, depression, anxiety, restlessness, decreased concentration, catatonia, hallucinations, time and place disorientation, emotional lability, clouded sensorium (bisoprolol); vertigo, paresthesia, restlessness (hydrochlorothiazide).
	dermatologic: Cutaneous vasculitis; rash, acne, eczema, psoriasis, skin irritation, pruritus, purpura, flushing, sweating, alopecia, dermatitis (bisoprolol); photosensitivity (hydrochlorothiazide).
	gi: Diarrhea; constipation; nausea; dyspepsia; gastric, epigastric, and abdominal pain, peptic ulcer, gastritis, vomiting, dry mouth, taste abnormalities, mesenteric arterial thrombosis, ischemic colitis (bisoprolol); anorexia, gastric irritation, cramping, pancreatitis, sialadenitis, dry mouth (hydrochlorothiazide).
	gu: Cystitis, renal colic, polyuria (bisoprolol); sexual dysfunction, renal failure, renal function impairment, interstitial nephritis (hydrochlorothiazide).
	hematologic: Agranulocytosis, thrombocytopenia; leukopenia, aplastic anemia, hemolytic anemia (hydrochlorothiazide).
	hepatic: Jaundice, cholecystitis (hydrochlorothiazide).
	eent: Rhinitis; pharyngitis, sinusitis, visual disturbances, ocular pain and pressure, abnormal lacrimation, tinnitus, decreased hearing, earache (bisoprolol); transient blurred vision, xanthopsia (hydrochlorothiazide).
	metabolic: Gout; increased serum triglycerides; small decrease in HDL cholesterol; weight gain (bisoprolol); hyperglycemia, glucosuria, edema, hyperuricemia, hypokalemia, hyperlipidemia, hypercalcemia (hydrochlorothiazide).
	respiratory: Bronchospasm; cough; upper respiratory infection; asthma, bronchitis, dyspnea (bisoprolol).
	miscellaneous: Asthenia; peripheral edema; muscle cramps; myalgia; arthralgia, muscle and joint pain, back and neck pain, twitching, tremor, malaise, allergy (fever, aching, sore throat, laryngospasm, respiratory distress) (bisoprolol); weakness, muscle spasm, hypersensitivity (purpura, photosensitivity, rash, urticaria, necrotizing angitis [vasculitis and cutaneous vasculitis], fever, respiratory distress [including pneumonitis and pulmonary edema], anaphylactic reaction) (hydrochlorothiazide).
Precautions:
	Monitoring: Monitor blood sugar in diabetic patient when drug is started or dose is changed. Report significant changes to health care provider. Withhold drug and notify health care provider if the following symptoms occur: hypotension, bradycardia, difficulty breathing, edema of hands or feet.
	Pregnancy: Category C .
	Lactation:
	Bisoprolol Undetermined.
	Hydrochlorothiazide Excreted in breast milk.
	Children: Safety and efficacy not established.
	Renal function impairment: Dosage adjustment or discontinuation may be necessary; azotemia may be precipitated.
	Hepatic function impairment: Use with caution.
	Cardiac failure Use with caution if therapy cannot be avoided.
	Abrupt cessation of therapy Exacerbations of angina pectoris and MI or ventricular arrhythmias may occur in patients with coronary artery disease following abrupt cessation of therapy.
	Peripheral vascular disease Precipitation or exacerbation of symptoms of arterial insufficiency in patients with peripheral vascular disease may occur.
	Bronchospastic disease Use with caution if therapy cannot be avoided.
	Diabetes and hypoglycemia May mask symptoms of hypoglycemia.
	Thyrotoxicosis May mask clinical signs of hyperthyroidism (eg, tachycardia).
Overdosage:	Signs & symptoms Bradycardia, hypotension, lethargy, delirium, coma, convulsions, respiratory arrest, CHF, bronchospasm, hypoglycemia, acute loss of fluid and electrolytes (eg, hypokalemia, hyponatremia, hypochloremia), tachycardia, shock, weakness, confusion, dizziness, calf cramps, paresthesia, fatigue, impaired consciousness, nausea, vomiting, thirst, polyuria, oliguria, anuria, alkalosis, increased BUN.
Patient/Family Education:	Advise patient to take medication every day as prescribed, without regard to meals. Advise patient to try to take each dose at the same time every 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 to do so by health care provider. Instruct patient to not interrupt therapy or discontinue drug abruptly. Instruct patient to continue taking other BP medications as prescribed by health care provider. Instruct patient in blood pressure and pulse measurement skills. Advise patient to monitor and record BP and pulse at home. Patient should 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 diabetic patient to monitor blood glucose more frequently when drug is started or dose is changed. Patient should 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. Advise patient that impotence or decreased libido are possible adverse reactions and to notify health provider if either occur. Emphasize to hypertensive patient importance of other modalities on BP (eg, weight control, regular exercise, smoking cessation, moderate intake of alcohol and salt). Instruct patient to report any of these symptoms to health care provider: difficulty breathing, slow heart rate, or swelling of ankles or feet. Advise patient that drug may cause drowsiness or dizziness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.