DRUG INTERACTIONS
Bisoprolol
Concurrent use of rifampin increases the metabolic clearance of bisoprolol, shortening its elimination half-life. However, initial dose modification is generally not necessary. Pharmacokinetic studies document no clinically relevant interactions with other agents given concomitantly, including thiazide diuretics, digoxin and cimetidine. There was no effect of bisoprolol on prothrombin times in patients on stable doses of warfarin.
Risk of Anaphylactic Reaction: While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reactions.
Hydrochlorothiazide
When given concurrently the following drugs may interact with thiazide diuretics. Alcohol, barbiturates, or narcotics - potentiation of orthostatic hypotension may occur.
Antidiabetic drugs (oral agents and insulin) - dosage adjustment of the antidiabetic drug may be required.
Other antihypertensive drugs - additive effect or potentiation.
Cholestyramine and colestipol resins - Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of cholestyramine and colestipol resins bind the hydrochlorothiazide and reduces its absorption in the gastrointestinal tract by up to 85 and 43 percent, respectively.
Cortocosteroids, ACTH - Intensified electrolyte depletion, particularly hypokalemia.
Pressor amines (eg, norepinephrine) - possible decreased response to pressor amines but not sufficient to preclude their use.
Skeletal muscle relaxants, nondepolarizing (eg, tubocurarine) - possible increased responsiveness to the muscle relaxant.
Lithium - generally should not be given with diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity. Refer to the package insert for lithium preparations before use of such preparations with bisoprolol and hydrochlorothiazide.
Nonsteroidal anti-inflammatory drugs - In some patients, the administration of a nonsteroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium sparing and thiazide diuretics. Therefore, when bisoprolol and hydrochlorothiazide and nonsteroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.
In patients receiving thiazides, sensitivity reactions may occur with or without a history of allergy or bronchial asthma. Photosensitivity reactions and possible exacerbation or activation of systemic lupus erythematosus have been reported in patients receiving thiazides. The antihypertensive effects of thiazides may be enhanced in the post-sympathectomy patient.
|
OVERDOSAGE
There are limited data on overdose with bisoprolol and hydrochlorothiazide. However, several cases of overdose with bisoprolol have been reported (maximum: 2000 mg). Bradycardia and/or hypotension were noted. Sympathomimetic agents were given in some cases, and all patients recovered.
The most frequently observed signs expected with overdosage of a beta-blocker are bradycardia and hypotension. Lethargy is also common, and with severe overdoses, delirium, coma, convulsions, and respiratory arrest have been reported to occur. Congestive heart failure, bronchospasm, and hypoglycemia may occur, particularly in patients with underlying conditions. With thiazide diuretics, acute intoxication is rare. The most prominent feature of overdose is acute loss of fluid and electrolytes. Signs and symptoms include cardiovascular (tachycardia, hypotension, shock), neuromuscular (weakness, confusion, dizziness, cramps of the calf muscles, paresthesia, fatigue, impairment of consciousness), gastrointestinal (nausea, vomiting, thirst) renal (polyuria, oliguria, or anuria [due to hemoconcentration]), and laboratory findings (hypokalemia, hyponatremia, hypochloremia, alkalosis, increased BUN [especially in patients with renal insufficiency]).
If overdosage of bisoprolol and hydrochlorothiazide is suspected, therapy with bisoprolol and hydrochlorothiazide should be discontinued and the patient observed closely. Treatment is symptomatic and supportive; there is no specific antidote. Limited data suggest bisoprolol is not dialyzable; similarly, there is no indication that hydrochlorothiazide is dialyzable. Suggested general measures include induction of emesis and/or gastric lavage, administration of activated charcoal, respiratory support, correction of fluid and electrolyte imbalance, and treatment of convulsions. Based on the expected pharmacologic actions and recommendations for other betablockers and hydrochlorothiazide, the following measures should be considered when clinically warranted.
Bradycardia: Administer IV atropine. If the response is inadequate, isoproterenol or another agent with positive chronotropic properties may be given cautiously. Under some circumstances, transvenous pacemaker insertion may be necessary.
Hypotension, Shock: The patient’s legs should be elevated. IV fluids should be administered and lost electrolytes (potassium, sodium) replaced. Intravenous glucagon may be useful. Vasopressors should be considered.
Heart Block (second or third degree): Patients should be carefully monitored and treated with isoproterenol infusion or transvenous cardiac pacemaker insertion, as appropriate.
Congestive Heart Failure: Initiate conventional therapy (ie, digitalis, diuretics, vasodilating agents, inotropic agents).
Bronchospasm: Administer a bronchodilator such as isoproterenol and/or aminophylline.
Hypoglycemia: Administer IV glucose.
Surveillance: Fluid and electrolyte balance (especially serum potassium) and renal function should be monitored until normalized.
|
