Bisoprolol fumarate/Hydrochlorothiazide

Description

Bisoprolol fumarate and hydrochlorothiazide tablets USP are indicated for the treatment of hypertension, combining two antihypertensive agents in a once-daily dosage. The formulation includes bisoprolol fumarate, a synthetic beta 1-selective (cardioselective) adrenoceptor blocking agent, and hydrochlorothiazide, a benzothiadiazine diuretic.

Bisoprolol fumarate is chemically described as (±)-1-[4-[-2-(1-methylethoxy)ethoxymethyl]phenoxy]-3-(1-methylethyl)amino-2-propanol(E)-2-butenedioate(2:1)(salt). It is a racemic mixture with an asymmetric carbon atom, where the S(-) enantiomer is primarily responsible for the beta-blocking activity. The molecular formula is (C18H31NO4)2•C4H4O4, and it has a molecular weight of 766.97. Bisoprolol fumarate appears as a white crystalline powder, exhibiting approximately equal hydrophilicity and lipophilicity, and is readily soluble in water, methanol, ethanol, and chloroform.

Hydrochlorothiazide (HCTZ) is identified as 6-Chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. It is a white or practically white, practically odorless crystalline powder. Hydrochlorothiazide is slightly soluble in water, sparingly soluble in dilute sodium hydroxide solution, freely soluble in n-butylamine and dimethylformamide, sparingly soluble in methanol, and insoluble in ether, chloroform, and dilute mineral acids. Its molecular formula is C7H8ClN3O4S2, with a molecular weight of 297.73.

Each Bisoprolol Fumarate and Hydrochlorothiazide tablet USP is available in three strengths for oral administration: 2.5 mg/6.25 mg, 5 mg/6.25 mg, and 10 mg/6.25 mg. The 2.5 mg/6.25 mg tablet contains 2.5 mg of bisoprolol fumarate and 6.25 mg of hydrochlorothiazide, while the 5 mg/6.25 mg tablet contains 5 mg of bisoprolol fumarate and 6.25 mg of hydrochlorothiazide. The 10 mg/6.25 mg tablet contains 10 mg of bisoprolol fumarate and 6.25 mg of hydrochlorothiazide.

Inactive ingredients in the tablets include pregelatinized starch, dibasic calcium phosphate anhydrous, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, colloidal silicon dioxide, copovidone, and titanium dioxide. The 5 mg/6.25 mg tablet also contains red and yellow iron oxide, while the 2.5 mg/6.25 mg tablet contains yellow iron oxide.

Uses and Indications

Bisoprolol fumarate and hydrochlorothiazide tablets are indicated for the management of hypertension. This combination therapy is intended for use in patients requiring blood pressure control.

Dosage and Administration

Bisoprolol is administered orally once daily, with effective dosing ranging from 2.5 mg to 40 mg. Hydrochlorothiazide is also administered orally, with effective doses between 12.5 mg and 50 mg.

For patients initiating antihypertensive therapy, it is recommended to start with the lowest dose of the bisoprolol fumarate and hydrochlorothiazide combination, specifically one 2.5/6.25 mg tablet once daily.

In clinical trials involving bisoprolol/hydrochlorothiazide combination therapy, bisoprolol doses ranged from 2.5 mg to 20 mg, while hydrochlorothiazide doses ranged from 6.25 mg to 25 mg. Subsequent titration of the bisoprolol fumarate and hydrochlorothiazide tablets may be performed, allowing for an increase up to the maximum recommended dose of 20/12.5 mg (equivalent to two 10/6.25 mg tablets) once daily, as deemed appropriate for the patient's condition.

Contraindications

Bisoprolol fumarate and hydrochlorothiazide tablets are contraindicated in patients with the following conditions:

• Cardiogenic shock

• Overt cardiac failure

• Second or third degree AV block

• Marked sinus bradycardia

• Anuria

• Hypersensitivity to either component of this product or to other sulfonamide-derived drugs

Use in these conditions is contraindicated due to the potential for exacerbating cardiac function or causing severe adverse reactions.

Warnings and Precautions

In general, beta-blocking agents should be avoided in patients with overt congestive heart failure; however, in select patients with compensated cardiac failure, the use of these agents may be necessary. In such cases, careful monitoring and cautious administration are essential. Continued depression of myocardial function with beta-blockers can precipitate cardiac failure in some patients. Therefore, at the first signs or symptoms of heart failure, discontinuation of bisoprolol fumarate and hydrochlorothiazide should be considered. In certain instances, therapy may be continued while heart failure is managed with alternative medications.

Patients with coronary artery disease are at risk for exacerbations of angina pectoris, and in some cases, myocardial infarction or ventricular arrhythmia, following abrupt cessation of beta-blocker therapy. Consequently, these patients should be advised against interrupting or discontinuing therapy without consulting their physician. For patients without overt coronary artery disease, it is advisable to taper bisoprolol fumarate and hydrochlorothiazide over approximately one week, with the patient under careful observation. Should withdrawal symptoms arise, reinstitution of beta-blocking agent therapy may be necessary, at least temporarily.

Beta-blockers can exacerbate symptoms of arterial insufficiency in patients with peripheral vascular disease; therefore, caution is warranted in this population. Additionally, patients with bronchospastic pulmonary disease should generally avoid beta-blockers. However, due to the relative beta1-selectivity of bisoprolol fumarate, it may be used cautiously in patients with bronchospastic disease who do not respond to or cannot tolerate other antihypertensive treatments. The lowest effective dose should be utilized, and a beta2 agonist (bronchodilator) should be readily available.

Chronic beta-blocking therapy should not routinely be withdrawn prior to major surgery, as the heart's impaired ability to respond to reflex adrenergic stimuli may increase the risks associated with general anesthesia and surgical procedures. Furthermore, beta-blockers may mask certain manifestations of hypoglycemia, particularly tachycardia. While the risk is lower with bisoprolol fumarate due to its beta1-selectivity, patients with a history of spontaneous hypoglycemia or those with diabetes receiving insulin or oral hypoglycemic agents should be made aware of these potential effects. Additionally, thiazides may necessitate adjustments in insulin dosing for diabetic patients, although the low dose of hydrochlorothiazide used in this combination may mitigate this risk.

Beta-adrenergic blockade can also mask clinical signs of hyperthyroidism, such as tachycardia. Abrupt withdrawal of beta-blockade may lead to exacerbation of hyperthyroid symptoms or precipitate a thyroid storm. In patients with impaired renal function, cumulative effects of thiazides may develop, potentially leading to azotemia. In individuals with creatinine clearance less than 40 mL/min, the plasma half-life of bisoprolol fumarate may increase up to threefold compared to healthy subjects. If progressive renal impairment is observed, discontinuation of bisoprolol fumarate and hydrochlorothiazide should be considered.

Caution is advised when using bisoprolol fumarate and hydrochlorothiazide in patients with impaired hepatic function or progressive liver disease, as thiazides can disrupt fluid and electrolyte balance, potentially precipitating hepatic coma. The elimination of bisoprolol fumarate is significantly slower in patients with cirrhosis than in healthy individuals.

Hydrochlorothiazide, a sulfonamide, may cause an idiosyncratic reaction leading to acute transient myopia and acute angle-closure glaucoma. Symptoms may include a sudden decrease in visual acuity or ocular pain, typically occurring within hours to weeks of initiating treatment. Untreated acute angle-closure glaucoma can result in permanent vision loss. The primary course of action is to discontinue hydrochlorothiazide as quickly as possible, and prompt medical or surgical intervention may be necessary if intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma include a history of sulfonamide or penicillin allergy.

At the first signs or symptoms of heart failure, discontinuation of bisoprolol fumarate and hydrochlorothiazide should be considered. If withdrawal symptoms occur, beta-blocking agent therapy should be reinstated, at least temporarily. In cases of progressive renal impairment, discontinuation of bisoprolol fumarate and hydrochlorothiazide is warranted. For acute angle-closure glaucoma, the immediate discontinuation of hydrochlorothiazide is essential, with prompt medical or surgical treatments considered if intraocular pressure remains uncontrolled.

Side Effects

Patients may experience a range of adverse reactions, which can be categorized by seriousness and frequency.

Serious adverse reactions include cardiovascular events such as bradycardia, arrhythmia, peripheral ischemia, and chest pain. Other serious reactions may involve respiratory issues like bronchospasm and dyspnea on exertion, as well as gastrointestinal complications such as peptic ulcer and pancreatitis. Dermatological reactions can also be severe, including erythema multiforme, Stevens-Johnson syndrome, and exfoliative dermatitis, which may manifest as toxic epidermal necrolysis.

Common adverse reactions reported in clinical trials and postmarketing experiences include central nervous system effects such as dizziness, headache, insomnia, and somnolence. Patients may also report gastrointestinal symptoms like diarrhea, nausea, and dyspepsia. Additionally, body-related reactions such as asthenia, fatigue, and peripheral edema are frequently observed.

Other notable adverse reactions encompass musculoskeletal complaints, including muscle cramps and myalgia, as well as psychiatric effects such as loss of libido, impotence, and anxiety/restlessness. Respiratory symptoms may also include cough, rhinitis, and upper respiratory infections.

Additional adverse reactions that have been noted include unsteadiness, vertigo, syncope, paresthesia, hypoesthesia, and hyperesthesia. Patients may experience sleep disturbances, vivid dreams, and decreased concentration or memory. Cardiovascular concerns may extend to palpitations, cold extremities, claudication, hypotension, and orthostatic hypotension, particularly when combined with alcohol, barbiturates, or narcotics.

Gastrointestinal disturbances may also present as gastric pain, vomiting, constipation, and dry mouth. Dermatological issues can include rash, acne, eczema, psoriasis, and pruritus, along with rare occurrences of cutaneous vasculitis. Visual disturbances, tinnitus, and taste abnormalities have also been reported.

Endocrine and metabolic reactions may involve hyperglycemia, glycosuria, hyperuricemia, and various electrolyte imbalances. Hematological concerns such as leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia, and hemolytic anemia have been documented as well.

Patients should be monitored for these adverse reactions, and any severe or persistent symptoms should be reported to a healthcare provider for further evaluation and management.

Drug Interactions

Concomitant use of bisoprolol fumarate and hydrochlorothiazide with other antihypertensive agents may enhance their effects, necessitating careful monitoring of blood pressure and potential dosage adjustments. It is advised that bisoprolol fumarate and hydrochlorothiazide not be used in combination with other beta-blocking agents due to the risk of additive effects.

Patients receiving catecholamine-depleting medications, such as reserpine or guanethidine, should be closely monitored for excessive sympathetic activity reduction when bisoprolol fumarate is administered. In cases where clonidine therapy is to be discontinued, it is recommended that bisoprolol fumarate and hydrochlorothiazide be withdrawn several days prior to the cessation of clonidine to mitigate withdrawal effects.

Caution is warranted when bisoprolol fumarate and hydrochlorothiazide are used alongside myocardial depressants or agents that inhibit atrioventricular conduction, including certain calcium antagonists (e.g., verapamil, diltiazem) and antiarrhythmic drugs (e.g., disopyramide). The concurrent use of digitalis glycosides with beta-blockers may increase the risk of bradycardia due to their combined effects on atrioventricular conduction and heart rate.

The use of rifampin may increase the metabolic clearance of bisoprolol fumarate, resulting in a shortened elimination half-life; however, initial dose adjustments are generally not required. No clinically significant interactions have been observed with other agents, including thiazide diuretics and cimetidine.

Hydrochlorothiazide may potentiate orthostatic hypotension when used with alcohol, barbiturates, or narcotics. Additionally, antidiabetic medications, both oral and insulin, may require dosage adjustments when administered with hydrochlorothiazide. Other antihypertensive drugs may exhibit additive effects when used concurrently with hydrochlorothiazide.

Cholestyramine and colestipol resins can significantly impair the absorption of hydrochlorothiazide, reducing gastrointestinal absorption by up to 85% and 43%, respectively. The use of corticosteroids and ACTH alongside hydrochlorothiazide may lead to intensified electrolyte depletion, particularly hypokalemia.

Pressor amines, such as norepinephrine, may demonstrate a decreased response when used with hydrochlorothiazide; however, this does not contraindicate their use. Nonsteroidal anti-inflammatory drugs may diminish the diuretic, natriuretic, and antihypertensive effects of thiazide diuretics, warranting close patient observation.

It is important to note that bisoprolol fumarate and hydrochlorothiazide may lower serum levels of protein-bound iodine without causing thyroid disturbances. Furthermore, these medications should be discontinued prior to conducting tests for parathyroid function to ensure accurate results.

Packaging & NDC

The table below lists all NDC Code configurations of Bisoprolol Fumarate and Hydrochlorothiazide, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of bisoprolol fumarate and hydrochlorothiazide in pediatric patients have not been established. Therefore, caution is advised when considering the use of this medication in children and adolescents. Further studies are necessary to determine appropriate dosing and therapeutic outcomes in this population.

Geriatric Use

In clinical trials, at least 270 patients aged 60 years and older were treated with bisoprolol fumarate in combination with hydrochlorothiazide (HCTZ). The addition of HCTZ significantly enhanced the antihypertensive effect of bisoprolol in elderly hypertensive patients.

No overall differences in effectiveness or safety were observed between geriatric patients and their younger counterparts. However, it is important to note that while clinical experience has not identified significant differences in responses between elderly and younger patients, greater sensitivity in some older individuals cannot be ruled out.

Healthcare providers should exercise caution when prescribing this combination to elderly patients, considering the potential for increased sensitivity and the need for careful monitoring of therapeutic responses.

Pregnancy

Bisoprolol fumarate and hydrochlorothiazide are classified as Pregnancy Category C, indicating that these agents should be used during pregnancy only if the potential benefits justify the risks to the fetus. There are no adequate and well-controlled studies in pregnant women to assess the safety of this combination.

Animal studies have shown that the bisoprolol fumarate/hydrochlorothiazide (B/H) combination is not teratogenic in rats at doses up to 51.4 mg/kg/day of bisoprolol fumarate combined with 128.6 mg/kg/day of hydrochlorothiazide. However, at lower doses of B 5.7/H 14.3 (mg/kg/day) and higher, the combination exhibited maternotoxic effects, including decreased body weight and food consumption, and fetotoxic effects, such as increased late resorptions at B 17.1/H 42.9 (mg/kg/day) and higher. In rabbits, the B/H combination was not teratogenic at doses of B 10/H 25 (mg/kg/day) but demonstrated maternotoxicity at B 1/H 2.5 (mg/kg/day) and higher, along with fetotoxicity indicated by increased resorptions at B 10/H 25 (mg/kg/day).

Bisoprolol fumarate alone has been shown to be non-teratogenic in rats at doses up to 150 mg/kg/day; however, it was fetotoxic at 50 mg/kg/day and maternotoxic at 150 mg/kg/day. In rabbits, bisoprolol fumarate was not teratogenic at doses up to 12.5 mg/kg/day but was associated with embryolethality, as evidenced by increased early resorptions at this dose.

Hydrochlorothiazide has been administered to pregnant mice and rats during major organogenesis at doses up to 3000 and 1000 mg/kg/day, respectively, without evidence of harm to the fetus. Nonetheless, due to the limitations of animal reproduction studies in predicting human responses, hydrochlorothiazide should be used during pregnancy only if clearly needed.

Healthcare professionals should carefully weigh the potential benefits against the risks when considering the use of bisoprolol fumarate and hydrochlorothiazide in pregnant patients.

Lactation

Bisoprolol fumarate, either alone or in combination with hydrochlorothiazide (HCTZ), has not been studied in nursing mothers. Thiazides are known to be excreted in human breast milk. In lactating rats, small amounts of bisoprolol fumarate (less than 2% of the dose) have been detected in breast milk. Due to the potential for serious adverse reactions in breastfed infants, healthcare professionals should consider whether to discontinue nursing or to discontinue the drug, weighing the importance of the medication to the mother.

Renal Impairment

Patients with renal impairment may experience cumulative effects of thiazides, which can precipitate azotemia. In individuals with a creatinine clearance of less than 40 mL/min, the plasma half-life of bisoprolol fumarate is increased up to threefold compared to healthy subjects. Therefore, if progressive renal impairment is observed, it is recommended that bisoprolol fumarate and hydrochlorothiazide be discontinued to mitigate potential risks associated with reduced kidney function.

Hepatic Impairment

Patients with hepatic impairment should use bisoprolol fumarate and hydrochlorothiazide with caution. It is important to monitor these patients closely due to the potential for altered fluid and electrolyte balance associated with thiazide use, which may precipitate hepatic coma.

In patients with cirrhosis, the elimination of bisoprolol fumarate is significantly slower compared to healthy subjects. Therefore, dosage adjustments may be necessary, and careful monitoring of liver function is recommended to ensure safety and efficacy in this population.

Overdosage

In cases of suspected overdosage with bisoprolol fumarate and hydrochlorothiazide, it is essential to recognize the potential symptoms and implement appropriate management strategies. Although data on overdose incidents are limited, several cases involving bisoprolol fumarate have been documented, with a maximum reported dose of 2000 mg. The most frequently observed symptoms associated with beta-blocker overdose include bradycardia and hypotension. Additional symptoms may encompass lethargy, and in severe instances, delirium, coma, convulsions, and respiratory arrest have been reported. Patients with pre-existing conditions may also experience congestive heart failure, bronchospasm, and hypoglycemia.

Thiazide diuretics, while less commonly associated with acute intoxication, can lead to significant fluid and electrolyte imbalances. The primary manifestations of thiazide overdose include cardiovascular symptoms such as tachycardia, hypotension, and shock, as well as neuromuscular symptoms like weakness, confusion, dizziness, calf muscle cramps, paresthesia, and fatigue. Gastrointestinal symptoms may include nausea, vomiting, and thirst, while renal effects can range from polyuria to oliguria or anuria, particularly due to hemoconcentration. Laboratory findings may reveal hypokalemia, hyponatremia, hypochloremia, alkalosis, and increased blood urea nitrogen (BUN), especially in patients with renal insufficiency.

Upon suspicion of overdosage, it is crucial to discontinue therapy with bisoprolol fumarate and hydrochlorothiazide and closely monitor the patient. Management should be symptomatic and supportive, as there is no specific antidote available. Current evidence suggests that bisoprolol fumarate is not dialyzable, and similarly, hydrochlorothiazide does not appear to be dialyzable. General measures to consider include the induction of emesis and/or gastric lavage, administration of activated charcoal, respiratory support, and correction of fluid and electrolyte imbalances. Additionally, treatment of convulsions may be necessary. Clinicians should consider these measures based on the pharmacologic actions of bisoprolol and hydrochlorothiazide, as well as established recommendations for managing overdoses of other beta-blockers and thiazide diuretics.

Nonclinical Toxicology

Thiazides are known to cross the placental barrier and can be detected in cord blood. The administration of thiazides in pregnant women necessitates a careful evaluation of the anticipated benefits against potential risks to the fetus. These risks may include fetal or neonatal jaundice, pancreatitis, thrombocytopenia, and possibly other adverse reactions that have been observed in adult populations.

Postmarketing Experience

A variety of adverse events (AEs) have been reported in clinical trials and postmarketing experience, in addition to those previously listed. While the causal relationship between bisoprolol and these AEs is not established, they are included to inform healthcare professionals of potential associations.

Central Nervous System: Reports include unsteadiness, dizziness, vertigo, headache, syncope, paresthesia, hypoesthesia, hyperesthesia, sleep disturbances, vivid dreams, insomnia, somnolence, depression, anxiety, restlessness, and decreased concentration or memory.

Cardiovascular: Observed events consist of bradycardia, palpitations, rhythm disturbances, cold extremities, claudication, hypotension, orthostatic hypotension, chest pain, congestive heart failure, and dyspnea on exertion.

Gastrointestinal: Adverse effects include gastric, epigastric, or abdominal pain, peptic ulcer, gastritis, dyspepsia, nausea, vomiting, diarrhea, constipation, and dry mouth.

Musculoskeletal: Reports of arthralgia, muscle or joint pain, back or neck pain, muscle cramps, and twitching or tremor have been noted.

Skin: Skin-related events include rash, acne, eczema, psoriasis, skin irritation, pruritus, purpura, flushing, sweating, alopecia, dermatitis, and very rarely, exfoliative dermatitis and cutaneous vasculitis.

Special Senses: Visual disturbances, ocular pain or pressure, abnormal lacrimation, tinnitus, decreased hearing, earache, and taste abnormalities have been reported.

Metabolic: Gout has been noted as a potential adverse effect.

Respiratory: Adverse events include asthma, bronchospasm, bronchitis, dyspnea, pharyngitis, rhinitis, sinusitis, and upper respiratory infections.

Genitourinary: Reports include decreased libido, impotence, Peyronie’s disease (very rarely), cystitis, renal colic, and polyuria.

General: Additional events reported include fatigue, asthenia, chest pain, malaise, edema, weight gain, and angioedema.

Furthermore, various adverse effects associated with other beta-adrenergic blocking agents should be considered as potential effects, including:

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

Allergic Reactions: Fever, aching, sore throat, laryngospasm, and respiratory distress have been reported.

Hematologic: Cases of agranulocytosis and thrombocytopenia have been noted.

Gastrointestinal: Mesenteric arterial thrombosis and ischemic colitis have been reported.

Miscellaneous: The oculomucocutaneous syndrome associated with practolol has not been reported with bisoprolol fumarate.

Additionally, adverse experiences associated with hydrochlorothiazide (generally at doses of 25 mg or greater) include:

General: Weakness.

Central Nervous System: Vertigo, paresthesia, and restlessness.

Cardiovascular: Orthostatic hypotension, potentially exacerbated by alcohol, barbiturates, or narcotics.

Gastrointestinal: Anorexia, gastric irritation, cramping, constipation, jaundice, pancreatitis, cholecystitis, sialadenitis, and dry mouth.

Musculoskeletal: Muscle spasm has been reported.

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

Special Senses: Transient blurred vision and xanthopsia have been noted.

Metabolic: Gout has been reported.

Genitourinary: Sexual dysfunction, renal failure, renal dysfunction, and interstitial nephritis have been observed.

Skin: Erythema multiforme, including Stevens-Johnson syndrome, and exfoliative dermatitis, including toxic epidermal necrolysis, have been reported.

Patient Counseling

Patients, particularly those with coronary artery disease, should be cautioned against discontinuing bisoprolol fumarate and hydrochlorothiazide without the supervision of a physician. It is essential for patients to understand the importance of consulting their healthcare provider if they experience any difficulty in breathing or develop other signs or symptoms indicative of congestive heart failure or excessive bradycardia.

For patients who are prone to spontaneous hypoglycemia or those with diabetes who are receiving insulin or oral hypoglycemic agents, it is important to inform them that beta-blockers, including bisoprolol fumarate, may mask certain manifestations of hypoglycemia, especially tachycardia. Therefore, these patients should use bisoprolol fumarate with caution.

Patients should also be advised to assess how this medication affects their ability to operate automobiles and machinery or engage in other activities that require alertness. Additionally, it is important to inform patients that photosensitivity reactions have been reported with thiazides, and they should take appropriate precautions.

Storage and Handling

The product is supplied in a tight container to ensure integrity and stability. It should be stored at a temperature range of 20°C to 25°C (68°F to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the quality and efficacy of the product.

Additional Clinical Information

Bisoprolol fumarate and hydrochlorothiazide may lead to a decrease in serum levels of protein-bound iodine without causing thyroid disturbances. Clinicians should ensure that these medications are discontinued prior to conducting tests for parathyroid function.

Patients, particularly those with coronary artery disease, must be cautioned against stopping bisoprolol fumarate and hydrochlorothiazide without medical supervision. They should seek medical advice if they experience breathing difficulties or symptoms indicative of congestive heart failure or excessive bradycardia. Additionally, patients with a history of spontaneous hypoglycemia or those on insulin or oral hypoglycemic agents should be aware that beta-blockers can mask hypoglycemia symptoms, especially tachycardia, necessitating cautious use of bisoprolol fumarate. Patients are also advised to understand their response to the medication before engaging in activities that require alertness, such as driving or operating machinery. Furthermore, it is important to inform patients that photosensitivity reactions have been associated with thiazide diuretics.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Bisoprolol Fumarate and Hydrochlorothiazide as submitted by Aidarex Pharmaceuticals LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)