Bisoprolol Fumarate Hydrochlorothiazide (Page 5 of 6)

Bisoprolol

In clinical trials worldwide, or in postmarketing experience, a variety of other AEs, in addition to those listed above, have been reported. While in many cases it is not known whether a causal relationship exists between bisoprolol and these AEs, they are listed to alert the physician to a possible relationship.

Central Nervous System: Unsteadiness, dizziness, vertigo, headache, syncope, paresthesia, hypoesthesia, hyperesthesia, sleep disturbance/vivid dreams, insomnia, somnolence, depression, anxiety/restlessness, decreased concentration/memory.

Cardiovascular: Bradycardia, palpitations and other rhythm disturbances, cold extremities, claudication, hypotension, orthostatic hypotension, chest pain, congestive heart failure, dyspnea on exertion.

Gastrointestinal: Gastric/epigastric/abdominal pain, peptic ulcer, gastritis, dyspepsia, nausea, vomiting, diarrhea, constipation, dry mouth.

Musculoskeletal: Arthralgia, muscle/joint pain, back/neck pain, muscle cramps, twitching/tremor.

Skin: Rash, acne, eczema, psoriasis, skin irritation, pruritus, purpura, flushing, sweating, alopecia, dermatitis, exfoliative dermatitis (very rarely), cutaneous vasculitis.

Special Senses: Visual disturbances, ocular pain/pressure, abnormal lacrimation, tinnitus, decreased hearing, earache, taste abnormalities.

Metabolic: Gout.

Respiratory: Asthma, bronchospasm, bronchitis, dyspnea, pharyngitis, rhinitis, sinusitis, URI (upper respiratory infection).

Genitourinary: Decreased libido/impotence, Peyronie’s disease (very rarely), cystitis, renal colic, polyuria.

General: Fatigue, asthenia, chest pain, malaise, edema, weight gain, angioedema.

In addition, a variety of adverse effects have been reported with other beta-adrenergic blocking agents and should be considered potential adverse effects:

Central Nervous System: Reversible mental depression progressing to catatonia, hallucinations, an acute reversible syndrome characterized by disorientation to time and place, emotional lability, slightly clouded sensorium.

Allergic: Fever, combined with aching and sore throat, laryngospasm, and respiratory distress.

Hematologic: Agranulocytosis, thrombocytopenia.

Gastrointestinal: Mesenteric arterial thrombosis and ischemic colitis.

Miscellaneous: The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with bisoprolol fumarate during investigational use or extensive foreign marketing experience.

Hydrochlorothiazide

The following adverse experiences, in addition to those listed in the above table, have been reported with hydrochlorothiazide (generally with doses of 25 mg or greater).

General: Weakness.

Central Nervous System: Vertigo, paresthesia, restlessness.

Cardiovascular: Orthostatic hypotension (may be potentiated by alcohol, barbiturates, or narcotics).

Gastrointestinal: Anorexia, gastric irritation, cramping, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis, cholecystitis, sialadenitis, dry mouth.

Musculoskeletal: Muscle spasm.

Hypersensitive Reactions: Purpura, photosensitivity, rash, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions.

Special Senses: Transient blurred vision, xanthopsia.

Metabolic: Gout.

Genitourinary: Sexual dysfunction, renal failure, renal dysfunction, interstitial nephritis.

Laboratory Abnormalities

Bisoprolol and hydrochlorothiazide:

Because of the low dose of hydrochlorothiazide in bisoprolol and hydrochlorothiazide, adverse metabolic effects with B/H6.25 mg are less frequent and of smaller magnitude than with HCTZ 25 mg. Laboratory data on serum potassium from the U.S. placebo-controlled trials are shown in the following table:

Serum Potassium Data from U.S. Placebo Controlled Studies
Placebo B2.5/H6.25 mg B5/H6.25 mg B10/H6.25 mg HCTZ25 mg
(n=130*) (n=28*) (n=149*) (n=28*) (n=142*)
* Patients with normal serum potassium at baseline.
a Mean change from baseline at Week 4.
b Percentage of patients with abnormality at Week 4.
Combined across studies.
Potassium
Mean Changea (mEq/L) +0.04 +0.11 -0.08 0.00 -0.30
% Hypokalemiab 0.0% 0.0% 0.7% 0.0% 5.5%

Treatment with both beta blockers and thiazide diuretics is associated with increases in uric acid. However, the magnitude of the change in patients treated with B/H 6.25 mg was smaller than in patients treated with HCTZ 25 mg. Mean increases in serum triglycerides were observed in patients treated with bisoprolol and hydrochlorothiazide 6.25 mg. Total cholesterol was generally unaffected, but small decreases in HDL cholesterol were noted.

Other laboratory abnormalities that have been reported with the individual components are listed below.

Bisoprolol

In clinical trials, the most frequently reported laboratory change was an increase in serum triglycerides, but this was not a consistent finding.

Sporadic liver test abnormalities have been reported. In the U.S. controlled trials experience with bisoprolol treatment for 4-12 weeks, the incidence of concomitant elevations in SGOT and SGPT of between 1-2 times normal was 3.9%, compared to 2.5% for placebo. No patient had concomitant elevations greater than twice normal.

In the long-term, uncontrolled experience with bisoprolol treatment for 6-18 months, the incidence of one or more concomitant elevations in SGOT and SGPT from 1 to 2 times normal was 6.2%. The incidence of multiple occurrence was 1.9%. For concomitant elevations in SGOT and SGPT of greater than twice normal, the incidence was 1.5%. The incidence of multiple occurrences was 0.3%. In many cases these elevations were attributed to underlying disorders, or resolved during continued treatment with bisoprolol.

Other laboratory changes included small increases in uric acid, creatinine, BUN, serum potassium, glucose, and phosphorus and decreases in WBC and platelets. There have been occasional reports of eosinophilia. These were generally not of clinical importance and rarely resulted in discontinuation of bisoprolol.

As with other beta-blockers, ANA conversions have also been reported on bisoprolol. About 15% of patients in long-term studies converted to a positive titer, although about one-third of these patients subsequently reconverted to a negative titer while on continued therapy.

Hydrochlorothiazide

Hyperglycemia, glycosuria, hyperuricemia, hypokalemia and other electrolyte imbalances (see PRECAUTIONS), hyperlipidemia, hypercalcemia, luekopenia, agranulocytosis, thrombocytopenia, aplastic anemia, and hemolytic anemia have been associated with HCTZ therapy.

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.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2022. All Rights Reserved.