Bisoprolol Fumarate and Hydrochlorothiazide 2.5 mg; 6.25 mg Tablet, 100-count
Other active recalls for Bisoprolol Fumarate And Hydrochlorothiazide (different manufacturers) — 2 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the beta-Adrenergic Blocker class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Bisoprolol is used to treat high blood pressure. Bisoprolol is in a class of medications called beta blockers. It works by relaxing blood vessels and slowing heart rate to improve and decrease blood pressure.
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII L11K75P92J
A mineral salt made from calcium and phosphate. It acts as a filler and binder in tablets to add bulk and help hold the medicine together in solid form.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII EX438O2MRT
Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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UNII O8232NY3SJ
A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
6 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $0.4132 | $41.32 / 100 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| bisoprolol fumarate and hydrochlorothiazide 2.5 mg/1; 6.25 mg 00093-3241-01 | Teva | 100 tablets | $0.215 | AB | Availability likely | — |
| Bisoprolol Fumarate and Hydrochlorothiazide 2.5 mg/1; 6.25 mg 00378-0501-01 | Mylan | 100 tablets | $0.215 | AB | Availability likely | — |
| bisoprolol fumarate and hydrochlorothiazide 6.25 mg/1; 2.5 mg 29300-0187-01 | Unichem | 100 tablets | $0.215 | AB | Availability likely | — |
| Bisoprolol Fumarate and Hydrochlorothiazide 2.5 mg/1; 6.25 mg 42799-0920-01 | Edenbridge | 100 tablets | $0.215 | AB | Availability likely | — |
| Bisoprolol Fumarate and Hydrochlorothiazide 2.5 mg/1; 6.25 mg 68462-0878-01 | GLENMARK | 100 tablets | $0.215 | AB | Availability likely | — |
| Bisoprolol Fumarate and Hydrochlorothiazide 2.5 mg/1; 6.25 mg 72578-0113-01 | Viona | 100 tablets | $0.215 | AB | Availability likely | — |
| Bisoprolol Fumarate and Hydrochlorothiazide 2.5 mg/1; 6.25 mg 70954-0412-10 | ANI | 30 tablets | $0.241 | AB | FDA listed | — |
| Bisoprolol Fumarate and Hydrochlorothiazide 2.5 mg/1; 6.25 mgthis 10135-0740-01 | Marlex | 100 tablets | — | AB | FDA listed | — |
| bisoprolol fumarate and hydrochlorothiazide 2.5 mg/1; 6.25 mg 50090-6478-00 | A-S | 30 tablets | — | AB | FDA listed | — |
| Bisoprolol Fumarate and Hydrochlorothiazide 2.5 mg/1; 6.25 mg 59651-0678-01 | Aurobindo | 100 tablets | — | AB | FDA listed | — |
| Bisoprolol Fumarate and Hydrochlorothiazide 2.5 mg/1; 6.25 mg 70771-1760-01 | Zydus | 100 tablets | — | AB | FDA listed | — |
| bisoprolol fumarate and hydrochlorothiazide 6.25 mg/1; 2.5 mg 71335-1161-01 | Bryant | 100 tablets | — | AB | Discontinued | — |
| Bisoprolol Fumarate and Hydrochlorothiazide 2.5 mg/1; 6.25 mg 71335-1931-01 | Bryant | 100 tablets | — | AB | FDA listed | — |
| Bisoprolol Fumarate and Hydrochlorothiazide 2.5 mg/1; 6.25 mg 71335-2616-01 | Bryant | 100 tablets | — | AB | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 10135-0740-01 You're viewing this | 100 TABLET in 1 BOTTLE (10135-740-01) | 2022-05-01 | Active |
| 10135-0740-05 | 500 TABLET in 1 BOTTLE (10135-740-05) | 2022-05-01 | Active |
You're viewing the smallest of 2 pack sizes for this product.
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
INDICATIONS & USAGE Bisoprolol fumarate and hydrochlorothiazide tablets are indicated in the management of hypertension.
⏱️ Dosage and Administration ▾
DOSAGE & ADMINISTRATION Bisoprolol is an effective treatment of hypertension in once-daily doses of 2.5 to 40 mg, while hydrochlorothiazide is effective in doses of 12.5 to 50 mg. In clinical trials of bisoprolol/hydrochlorothiazide combination therapy using bisoprolol doses of 2.5 to 20 mg and hydrochlorothiazide doses of 6.25 to 25 mg, the antihypertensive effects increased with increasing doses of either component. The adverse effects (see WARNINGS) of bisoprolol are a mixture of dose-dependent phenomena (primarily bradycardia, diarrhea, asthenia, and fatigue) and dose-independent phenomena (eg, occasional rash); those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose-independent phenomena (eg, possibly pancreatitis); the dose-dependent phenomenafor each being much more common than the dose-independent phenomena.
The latter consist of those few that are truly idiosyncratic in nature or those that occur with such low frequency that a dose relationship may be difficult to discern. Therapy with a combination of bisoprolol and hydrochlorothiazide will be associated with both sets of dose-independent adverse effects, and to minimize these, it may be appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy. On the other hand, regimens that combine low doses of bisoprolol and hydrochlorothiazide should produce minimal dose-dependent adverse effects, eg, bradycardia, diarrhea, asthenia and fatigue, and minimal dose-dependent adverse metabolic effects, ie, decreases in serum potassium (see CLINICAL PHARMACOLOGY).
Therapy Guided by Clinical Effect A patient whose blood pressure is not adequately controlled with 2.5-20 mg bisoprolol daily may instead be given bisoprolol fumarate and hydrochlorothiazide tablets. Patients whose blood pressures are adequately controlled with 50 mg of hydrochlorothiazide daily, but who experience significant potassium loss with this regimen, may achieve similar blood pressure control without electrolyte disturbance if they are switched to bisoprolol fumarate and hydrochlorothiazide tablets. Initial Therapy Antihypertensive therapy may be initiated with the lowest dose of bisoprolol fumarate and hydrochlorothiazide tablets, one 2.5/6.25 mg tablet once daily.
Subsequent titration (14 day intervals) may be carried out with bisoprolol fumarate and hydrochlorothiazide tablets up to the maximum recommended dose 20/12.5 mg (two 10/6.25 mg tablets) once daily, as appropriate. Replacement Therapy The combination may be substituted for the titrated individual components. Cessation of Therapy If withdrawal of bisoprolol fumarate and hydrochlorothiazide tablets therapy is planned, it should be achieved gradually over a period of about 2 weeks.
Patients should be carefully observed. Patients with Renal or Hepatic Impairment: As noted in the WARNINGS section, caution must be used in dosing/titrating patients with hepatic impairment or renal dysfunction. Since there is no indication that hydrochlorothiazide is dialyzable, and limited data suggest that bisoprolol is not dialyzable, drug replacement is not necessary in patients undergoing dialysis.
Geriatric Patients: Dosage adjustment on the basis of age is not usually necessary, unless there is also significant renal or hepatic dysfunction (see above and WARNINGS section). Pediatric Patients: There is no pediatric experience with bisoprolol fumarate and hydrochlorothiazide tablets.
⛔ Contraindications ▾
CONTRAINDICATIONS Bisoprolol fumarate and hydrochlorothiazide tablets are contraindicated in patients in cardiogenic shock, overt cardiac failure (see WARNINGS), second or third degree AV block, marked sinus bradycardia, anuria, and hypersensitivity to either component of this product or to other sulfonamide- derived drugs.
⚠️ Warnings ▾
WARNINGS Cardiac Failure In general, beta-blocking agents should be avoided in patients with overt congestive failure. However, in some patients with compensated cardiac failure, it may be necessary to utilize these agents. In such situations, they must be used cautiously.
Patients Without a History of Cardiac Failure Continued depression of the myocardium with beta-blockers can, in some patients, precipitate cardiac failure. At the first signs or symptoms of heart failure, discontinuation of bisoprolol fumarate and hydrochlorothiazide tablets should be considered. In some cases bisoprolol fumarate and hydrochlorothiazide tablets therapy can be continued while heart failure is treated with other drugs.
Abrupt Cessation of Therapy Exacerbations of angina pectoris and, in some instances, myocardial infarction or ventricular arrhythmia, have been observed in patients with coronary artery disease following abrupt cessation of therapy with beta-blockers. Such patients should, therefore, be cautioned against interruption or discontinuation of therapy without the physician’s advice. Even in patients without overt coronary artery disease, it may be advisable to taper therapy with bisoprolol fumarate and hydrochlorothiazide tablets over approximately 1 week with the patient under careful observation.
If withdrawal symptoms occur, beta-blocking agent therapy should be reinstituted, at least temporarily. Peripheral Vascular Disease Beta-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease. Caution should be exercised in such individuals.
Bronchospastic Disease PATIENTS WITH BRONCHOSPASTIC PULMONARY DISEASE SHOULD, IN GENERAL, NOT RECEIVE BETA-BLOCKERS. Because of the relative beta1-selectivity of bisoprolol fumarate, bisoprolol fumarate and hydrochlorothiazide tablets may be used with caution in patients with bronchospastic disease who do not respond to, or who cannot tolerate other antihypertensive treatment. Since beta1-selectivity is not absolute, the lowest possible dose of bisoprolol fumarate and hydrochlorothiazide tablets should be used.
A beta2 agonist (bronchodilator) should be made available. Major Surgery Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures. Diabetes and Hypoglycemia Beta-blockers may mask some of the manifestations of hypoglycemia, particularly tachycardia.
Nonselective beta-blockers may potentiate insulin-induced hypoglycemia and delay recovery of serum glucose levels. Because of its beta1-selectivity, this is less likely with bisoprolol fumarate. However, patients subject to spontaneous hypoglycemia, or diabetic patients receiving insulin or oral hypoglycemic agents, should be cautioned about these possibilities.
Also, latent diabetes mellitus may become manifest and diabetic patients given thiazides may require adjustment of their insulin dose. Because of the very low dose of HCTZ employed, this may be less likely with bisoprolol fumarate and hydrochlorothiazide tablets. Thyrotoxicosis Beta-adrenergic blockade may mask clinical signs of hyperthyroidism, such as tachycardia.
Abrupt withdrawal of beta-blockade may be followed by an exacerbation of the symptoms of hyperthyroidism or may precipitate thyroid storm. Renal Disease Cumulative effects of the thiazides may develop in patients with impaired renal function. In such patients, thiazides may precipitate azotemia.
In subjects with creatinine clearance less than 40 mL/min, the plasma half-life of bisoprolol fumarate is increased up to threefold, as compared to healthy subjects. If progressive renal impairment becomes apparent, bisoprolol fumarate and hydrochlorothiazide tablets should be discontinued (See Pharmacokinetics and Metabolism). Hepatic Disease Bisoprolol fumarate and hydrochlorothia…
🤒 Adverse Reactions ▾
ADVERSE REACTIONS Bisoprolol Fumarate and Hydrochlorothiazide Tablets Bisoprolol fumarate/HCTZ 6.25 mg is well tolerated in most patients. Most adverse effects (AEs) have been mild and transient. In more than 65,000 patients treated worldwide with bisoprolol fumarate, occurrences of bronchospasm have been rare.
Discontinuation rates for AEs were similar for bisoprolol fumarate/HCTZ 6.25 mg and placebo-treated patients. In the United States, 252 patients received bisoprolol fumarate (2.5, 5, 10, or 40 mg)/HCTZ 6.25 mg and 144 patients received placebo in two controlled trials. In Study 1, bisoprolol fumarate 5/HCTZ 6.25 mg was administered for 4 weeks.
In Study 2, bisoprolol fumarate 2.5, 10, or 40/HCTZ 6.25 mg was administered for 12 weeks. All adverse experiences, whether drug related or not, and drug related adverse experiences in patients treated with bisoprolol fumarate 2.5-10/HCTZ 6.25 mg, reported during comparable, 4 week treatment periods by at least 2% of bisoprolol fumarate/HCTZ 6.25 mg-treated patients (plus additional selected adverse experiences) are presented in the following table: % of Patients with Adverse Experiences a Body System/ AdverseExperience All AdverseExperiences Drug Related Adverse Experiences Placebo b B2.5-40/H6.25 b Placebo b B2.5-10/H6.25 b (n=144) (n=252) (n=144) (n=221) % % % % Cardiovascular bradycardia 0.7 1.1 0.7 0.9 arrhythmia 1.4 0.4 0.0 0.0 peripheral ischemia 0.9 0.7 0.9 0.4 chest pain 0.7 1.8 0.7
0.9Respiratory bronchospasm 0.0 0.0 0.0 0.0 cough 1.0 2.2 0.7 1.5 rhinitis 2.0 0.7 0.7
0.9URI 2.3 2.1 0.0
0.0Body as a Whole asthenia 0.0 0.0 0.0 0.0 fatigue 2.7 4.6 1.7 3.0 peripheral edema 0.7 1.1 0.7
0.9Central Nervous System dizziness 1.8 5.1 1.8 3.2 headache 4.7 4.5 2.7
0.4Musculoskeletal muscle cramps 0.7 1.2 0.7 1.1 myalgia 1.4 2.4 0.0
0.0Psychiatric insomnia 2.4 1.1 2.0 1.2 somnolence 0.7 1.1 0.7 0.9 loss of libido 1.2 0.4 1.2 0.4 impotence 0.7 1.1 0.7
1.1Gastrointestinal diarrhea 1.4 4.3 1.2 1.1 nausea 0.9 1.1 0.9 0.9 dyspepsia 0.7 1.2 0.7 0.9 a Averages adjusted to combine acrossstudies. b Combined acrossstudies. Other adverse experiences that have been reported with the individual components are listed below. Bisoprolol Fumarate 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 onexertion.
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 e…
🤰 Pregnancy ▾
PREGNANCY Teratogenic Effects Bisoprolol Fumarate and Hydrochlorothiazide Tablets In rats, the bisoprolol fumarate/hydrochlorothiazide (B/H) combination was not teratogenic at doses up to 51.4 mg/kg/day of bisoprolol fumarate in combination with 128.6 mg/kg/day of hydrochlorothiazide. Bisoprolol fumarate and hydrochlorothiazide doses used in the rat study are, as multiples of the MRHD in the combination, 129 and 514 times greater, respectively, on a body weight basis, and 26 and 106 times greater, respectively, on the basis of body surface area.
The drug combination was maternotoxic (decreased body weight and food consumption) at B5.7/H14.3 (mg/kg/day) and higher, and fetotoxic (increased late resorptions) at B17.1/H42.9 (mg/kg/day) and higher. Maternotoxicity was present at 14/57 times the MRHD of B/H, respectively, on a body weight basis, and 3/12 times the MRHD of B/H doses, respectively, on the basis of body surface area. Fetotoxicity was present at 43/172 times the MRHD of B/H, respectively, on a body weight basis, and 9/35 times the MRHD of B/H doses, respectively, on the basis of body surface area.
In rabbits, the B/H combination was not teratogenic at doses of B10/H25 (mg/kg/day). Bisoprolol fumarate and hydrochlorothiazide used in the rabbit study were not teratogenic at 25/100 times the B/H MRHD, respectively, on a body weight basis, and 10/40 times the B/H MRHD, respectively, on the basis of body surface area. The drug combination was maternotoxic (decreased body weight) at B1/H2.5 (mg/kg/day) and higher, and fetotoxic (increased resorptions) at B10/H25 (mg/kg/day).
The multiples of the MRHD for the B/H combination that were maternotoxic are, respectively, 2.5/10 (on the basis of body weight) and 1/4 (on the basis of body surface area), and for fetotoxicity were, respectively 25/100 (on the basis of body weight) and 10/40 (on the basis of body surface area). There are no adequate and well-controlled studies with bisoprolol fumarate and hydrochlorothiazide tablets in pregnant women. Bisoprolol fumarate and hydrochlorothiazide tablets should be used during pregnancy only if the potential benefit justifies the risk to the fetus.
Bisoprolol Fumarate In rats, bisoprolol fumarate was not teratogenic at doses up to 150 mg/kg/day, which were 375 and 77 times the MRHD on the basis of body weight and body surface area, respectively. Bisoprolol fumarate was fetotoxic (increased late resorptions) at 50 mg/kg/day and maternotoxic (decreased food intake and body weight gain) at 150 mg/kg/day. The fetotoxicity in rats occurred at 125 times the MRHD on a body weight basis and 26 times the MRHD on the basis of body surface area.
The maternotoxicity occurred at 375 times the MRHD on a body weight basis and 77 times the MRHD on the basis of body surface area. In rabbits, bisoprolol fumarate was not teratogenic at doses up to 12.5 mg/kg/day, which is 31 and 12 times the MRHD based on body weight and body surface area, respectively, but was embryolethal (increased early resorptions) at 12.5 mg/kg/day. Hydrochlorothiazide Hydrochlorothiazide was orally administered to pregnant mice and rats during respective periods of major organogenesis at doses up to 3000 and 1000 mg/kg/day, respectively.
At these doses, which are multiples of the MRHD equal to 12,000 for mice and 4000 for rats, based on body weight, and equal to 1129 for mice and 824 for rats, based on body surface area, there was no evidence of harm to the fetus. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Nonteratogenic Effects Thiazides cross the placental barrier and appear in the cord blood. The use of thiazides in pregnant women requires that the anticipated benefit be weighed against possible hazards to the fetus. These hazards include fetal or neonatal jaundice, pancreatitis, thrombocytopenia, and…
🧒 Pediatric Use ▾
PEDIATRIC USE Safety and effectiveness of bisoprolol fumarate and hydrochlorothiazide tablets in pediatric patients have not been established.
🧓 Geriatric Use ▾
GERIATRIC USE In clinical trials, at least 270 patients treated with bisoprolol fumarate plus HCTZ were 60 years of age or older. HCTZ added significantly to the antihypertensive effect of bisoprolol in elderly hypertensive patients. No overall differences in effectiveness or safety were observed between these patients and younger patients.
Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
🆘 Overdosage ▾
OVERDOSAGE There are limited data on overdose with bisoprolol fumarate and hydrochlorothiazide tablets. However, several cases of overdose with bisoprolol fumarate 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 fumarate and hydrochlorothiazide tablets is suspected, therapy with bisoprolol fumarate and hydrochlorothiazide tablets should be discontinued and the patient observed closely.
Treatment is symptomatic and supportive; there is no specific antidote. Limited data suggest bisoprolol fumarate 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 beta-blockers 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.
🧬 Clinical Pharmacology ▾
CLINICAL PHARMACOLOGY Bisoprolol fumarate and HCTZ have been used individually and in combination for the treatment of hypertension. The antihypertensive effects of these agents are additive; HCTZ 6.25 mg significantly increases the antihypertensive effect of bisoprolol fumarate. The incidence of hypokalemia with the bisoprolol fumarate and HCTZ 6.25 mg combination (B/H) is significantly lower than with HCTZ 25 mg.
In clinical trials of bisoprolol fumarate and hydrochlorothiazide tablets, mean changes in serum potassium for patients treated with bisoprolol fumarate and hydrochlorothiazide tablets 2.5/6.25 mg, 5/6.25 mg or 10/6.25 mg or placebo were less than ± 0.1 mEq/L. Mean changes in serum potassium for patients treated with any dose of bisoprolol in combination with HCTZ 25 mg ranged from -0.1 to -0.3 mEq/L. Bisoprolol fumarate is a beta1-selective (cardioselective) adrenoceptor blocking agent without significant membrane stabilizing or intrinsic sympathomimetic activities in its therapeutic dose range.
At higher doses (≥ 20 mg) bisoprolol fumarate also inhibits beta2-adrenoreceptors located in bronchial and vascular musculature. To retain relative selectivity, it is important to use the lowest effective dose. Hydrochlorothiazide is a benzothiadiazine diuretic.
Thiazides affect renal tubular mechanisms of electrolyte reabsorption and increase excretion of sodium and chloride in approximately equivalent amounts. Natriuresis causes a secondary loss of potassium. Pharmacokinetics and Metabolism Bisoprolol Fumarate and Hydrochlorothiazide Tablets In healthy volunteers, both bisoprolol fumarate and hydrochlorothiazide are well absorbed followingoral administration of bisoprolol fumarate and hydrochlorothiazide tablets.
No change is observed in the bioavailability of either agent when given together in a single tablet. Absorption is not affected whether bisoprolol fumarate and hydrochlorothiazide tablets are taken with or without food. Mean peak bisoprolol fumarate plasma concentrations of about 9.0 ng/mL, 19 ng/mL and 36 ng/mL occur approximately 3 hours after the administration of the 2.5 mg/6.25 mg, 5 mg/6.25 mg and 10 mg/6.25 mg combination tablets, respectively.
Mean peak plasma hydrochlorothiazide concentrations of 30 ng/mL occur approximately 2.5 hours following the administration of the combination. Dose proportional increases in plasma bisoprolol concentrations are observed between the 2.5 and 5, as well as between the 5 and 10 mg doses. The elimination T1/2 of bisoprolol ranges from 7 to 15 hours, and that of hydrochlorothiazide ranges from 4 to 10 hours.
The percent of dose excreted unchanged in urine is about 55% for bisoprolol and about 60% for hydrochlorothiazide. Bisoprolol Fumarate The absolute bioavailability after a 10 mg oral dose of bisoprolol fumarate is about 80%. The first pass metabolism of bisoprolol fumarate is about 20%.
The pharmacokinetic profile of bisoprolol fumarate has been examined following single doses and at steady state. Binding to serum proteins is approximately 30%. Peak plasma concentrations occur within 2-4 hours of dosing with 2.5 to 20 mg, and mean peak values range from 9.0 ng/mL at 2.5 mg to 70 ng/mL at 20 mg.
Once-daily dosing with bisoprolol fumarate results in less than twofold intersubject variation in peak plasma concentrations. Plasma concentrations are proportional to the administered dose in the range of 2.5 to 20 mg. The plasma elimination half-life is 9-12 hours and is slightly longer in elderly patients, in part because of decreased renal function.
Steady state is attained within 5 days with once-daily dosing. In both young and elderly populations, plasma accumulation is low; the accumulation factor ranges from 1.1 to 1.3, and is what would be expected from the half-life and once-daily dosing. Bisoprolol is eliminated equally by renal and nonrenal pathways with about 50% of the dose appearing unchanged in the urine and the remainder in the form of inactive metabolites.
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📦 How Supplied / Storage and Handling ▾
HOW SUPPLIED Bisoprolol Fumarate and Hydrochlorothiazide - 2.5 mg/6.25 mg Tablets, USP (bisoprolol fumarate 2.5 mg and hydrochlorothiazide 6.25 mg): Yellow, round, uncoated, unscored tablets debossed “N” and “412” on one side and plain on the other side, supplied as follows: Bottle of 100 Tablets NDC 10135-0740-01 Bottle of 500 Tablets NDC 10135-0740-05 Bisoprolol Fumarate and Hydrochlorothiazide - 5 mg/6.25 mg Tablets, USP (bisoprolol fumarate 5 mg and hydrochlorothiazide 6.25 mg): Pink, round, uncoated, unscored tablets debossed “N” and “413” on one side and plain on the other side, supplied as follows: Bottle of 100 Tablets NDC 10135-0741-01 Bottle of 500 Tablets NDC 10135-0741-05 Bisoprolol Fumarate and Hydrochlorothiazide - 10 mg/6.25 mg Tablets, USP (bisoprolol fumarate 10 mg and hydrochlorothiazide 6.25 mg): Blue, round, uncoated, unscored tablets debossed “N” and “414” on one side and plain on the other side, supplied as follows: Bottle of 30 Tablets NDC 10135-0742-30 Bottle of 500 Tablets NDC 10135-0742-05 Store at 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature].
Dispense in a tight container. Manufactured for/ Distributed by: Marlex Pharmaceuticals, Inc. New Castle, DE 19720 Rev.
05/22 NP
📋 Description ▾
DESCRIPTION Bisoprolol fumarate and hydrochlorothiazide tablets, USP are indicated for the treatment of hypertension. It combines two antihypertensive agents in a once-daily dosage: a synthetic beta 1 -selective (cardioselective) adrenoceptor blocking agent (bisoprolol fumarate) and a benzothiadiazine diuretic (hydrochlorothiazide). Bisoprolol fumarate is chemically described as (±)-1-[4-[[2-(1-methylethoxy)ethoxy]methyl] phenoxy]-3-[(1-methylethyl)amino]-2-propanol( E )-2-butenedioate (2:1) (salt).
It possesses an asymmetric carbon atom in its structure and is provided as a racemic mixture. The S(-) enantiomer is responsible for most of the beta-blocking activity. Its empirical formula is (C 18 H 31 NO 4 ) 2 •C 4 H 4 O 4 and it has a molecular weight of 766.97.
Its structural formula is: Bisoprolol fumarate is a white crystalline powder, approximately equally hydrophilic and lipophilic, and readily soluble in water, methanol, ethanol, and chloroform. Hydrochlorothiazide (HCTZ) is 6-Chloro-3,4-dihydro-2 H -1,2,4-benzothiadiazine-7-sulfonamide 1,1- dioxide. It is a white, or practically white, practically odorless crystalline powder.
It 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 empirical formula is C 7 H 8 ClN 3 O 4 S 2 and it has a molecular weight of 297.73. Its structural formula is: Each bisoprolol fumarate and hydrochlorothiazide - 2.5 mg/6.25 mg tablet, USP for oral administration contains: Bisoprolol fumarate…………………………………………..2.5 mg Hydrochlorothiazide………………………………………..6.25 mg Each bisoprolol fumarate and hydrochlorothiazide - 5 mg/6.25 mg tablet, USP for oral administration contains: Bisoprolol fumarate…………………………………………… 5 mg Hydrochlorothiazide………………………………………..
6.25mg Each bisoprolol fumarate and hydrochlorothiazide - 10 mg/6.25 mg tablet, USP for oral administration contains: Bisoprolol fumarate…………………………………………...10 mg Hydrochlorothiazide……………………………………….. 6.25 mg Inactive ingredients include pregelatinized starch, anhydrous dicalcium phosphate, magnesium stearate, microcrystalline cellulose, colloidal silicon dioxide. The 10 mg/6.25mg tablet also contains FD&C blue #1 aluminum lake.
The 5 mg/6.25 mg tablet also contains iron oxide red & ferrosoferric oxide. The 2.5 mg/6.25 mg tablet also contains ferric oxide. FDA approved dissolution test specifications differ from USP.
Bisoprolol-Fumarate thiazide-structure
💬 Information for Patients ▾
INFORMATION FOR PATIENTS Warn patients, especially those with coronary artery disease, against discontinuing use of bisoprolol fumarate and hydrochlorothiazide tablets without a physician’s supervision. Patients should also be advised to consult a physician if any difficulty in breathing occurs, or if they develop other signs or symptoms of congestive heart failure or excessive bradycardia. Caution patients subject to spontaneous hypoglycemia, or diabetic patients receiving insulin or oral hypoglycemic agents, that beta-blockers may mask some of the manifestations of hypoglycemia, particularly tachycardia, and bisoprolol fumarate should be used with caution.
Patients should know how they react to this medicine before they operate automobiles and machinery or engage in other tasks requiring alertness. Advise patients that photosensitivity reactions have been reported with thiazides. Non-melanoma Skin Cancer Instruct patients taking hydrochlorothiazide to protect skin from the sun and undergo regular skin cancer screening.
Acute Angle-Closure Glaucoma Instruct patients taking hydrochlorothiazide to immediately consult their healthcare provider if visual field defects, decreased visual acuity, or ocular pain occur.