Valsartan and Hydrochlorothiazide 320 mg; 25 mg Tablet, Film Coated, 30-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Thiazide Diuretic class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Hydrochlorothiazide is used alone or in combination with other medications to treat high blood pressure. Hydrochlorothiazide is used to treat edema (fluid retention; excess fluid held in body tissues) caused by various medical problems, including heart, kidney, and liver disease and to treat edema caused by using certain medications including estrogen and corticosteroids. Hydrochlorothiazide is in a class of medications called diuretics ('water pills'). It works by causing the kidneys to get rid of unneeded water and salt from the body into the urine. High blood pressure is a common condition...
Read the full MedlinePlus article ↗- This tablet combines two different blood pressure-lowering medicines in one pill: valsartan, which relaxes your blood vessels, and hydrochlorothiazide, a water pill that helps your...
- What exactly is this medication and why did my doctor prescribe it?
- You can take it either way — with or without food. The hydrochlorothiazide part isn't affected by food at all. Food does reduce how much valsartan your body absorbs, but since you...
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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 68401960MK
Crospovidone is a synthetic polymer made from polyvinylpyrrolidone. It acts as a disintegrant, helping tablets break apart quickly in the stomach so the medicine dissolves and absorbs into the body.
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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 R75537T0T4
Hypromellose 2910 is a plant-derived thickening agent made from cellulose. It serves as a binder that holds tablet ingredients together, a film-coating for pills, and a viscosity controller in liquids.
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UNII 0WZ8WG20P6
Hypromellose 2910 is a plant-based cellulose derivative that acts as a thickener, binder, and film-coating agent. It helps control how quickly the medicine dissolves and protects the tablet or capsule from moisture and light.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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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 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 4R4HFI6D95
Polyethylene glycol 4000 is a synthetic polymer derived from petroleum. It serves as a binder, filler, and lubricant in solid dosage forms, and helps control how quickly the medicine dissolves.
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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 368GB5141J
A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
12 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 | $0.3156 | $9.47 / 30 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Valsartan and Hydrochlorothiazide 320 mg/1; 25 mg 00378-6325-77 | Mylan | 90 tablets | $0.201 | AB | Availability likely | — |
| Valsartan and Hydrochlorothiazide 320 mg/1; 25 mg 33342-0078-10 | Macleods | 90 tablets | $0.201 | AB | Availability likely | — |
| Valsartan and Hydrochlorothiazide 320 mg/1; 25 mg 65862-0551-05 | Aurobindo | 500 tablets | $0.201 | — | Availability likely | — |
| Diovan HCT 320 mg/1; 25 mg 00078-0472-34 | Novartis | 90 tablets | $16.497 | AB | FDA listed | — |
| Valsartan and Hydrochlorothiazide 320 mg/1; 25 mg 42291-0969-90 | AvKARE | 90 tablets | — | AB | FDA listed | — |
| Valsartan And Hydrochlorothiazide 320 mg/1; 25 mg 43547-0315-03 | Solco | 30 tablets | — | AB | FDA listed | — |
| Valsartan and Hydrochlorothiazide 320 mg/1; 25 mg 46708-0457-10 | Alembic | 100 tablets | — | AB | FDA listed | — |
| Valsartan and Hydrochlorothiazide 320 mg/1; 25 mg 50090-5345-00 | A-S | 90 tablets | — | AB | FDA listed | — |
| Valsartan And Hydrochlorothiazide 320 mg/1; 25 mg 50090-7443-00 | A-S | 90 tablets | — | AB | FDA listed | — |
| Valsartan and Hydrochlorothiazide 320 mg/1; 25 mg 51655-0243-52 | Northwind | 30 tablets | — | AB | FDA listed | — |
| Valsartan and Hydrochlorothiazide 320 mg/1; 25 mg 51655-0655-52 | Northwind | 30 tablets | — | AB | FDA listed | — |
| Valsartan and Hydrochlorothiazide 320 mg/1; 25 mg 53746-0849-90 | Amneal | 90 tablets | — | AB | FDA listed | — |
| Valsartan and Hydrochlorothiazide 320 mg/1; 25 mg 62332-0083-10 | Alembic | 100 tablets | — | AB | FDA listed | — |
| Valsartan and Hydrochlorothiazide 320 mg/1; 25 mgthis 63187-0694-30 | Proficient | 30 tablets | — | AB | FDA listed | — |
| Valsartan and Hydrochlorothiazide 320 mg/1; 25 mg 65162-0849-03 | Amneal | 30 tablets | — | AB | FDA listed | — |
| valsartan and hydrochlorothiazide 320 mg/1; 25 mg 70771-1489-00 | Zydus | 1000 tablets | — | — | FDA listed | — |
| Valsartan and Hydrochlorothiazide 320 mg/1; 25 mg 71205-0015-30 | Proficient | 30 tablets | — | AB | FDA listed | — |
| Valsartan and Hydrochlorothiazide 320 mg/1; 25 mg 71335-0547-01 | Bryant | 30 tablets | — | AB | Discontinued | — |
| Valsartan and Hydrochlorothiazide 320 mg/1; 25 mg 71335-0853-01 | Bryant | 30 tablets | — | AB | FDA listed | — |
| Valsartan And Hydrochlorothiazide 320 mg/1; 25 mg 71335-2200-01 | Bryant | 30 tablets | — | AB | FDA listed | — |
| Valsartan And Hydrochlorothiazide 320 mg/1; 25 mg 50228-0151-05 | ScieGen | 500 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 |
|---|---|---|---|
| 63187-0694-30 You're viewing this | 30 TABLET, FILM COATED in 1 BOTTLE (63187-694-30) | 2016-04-01 | Active |
| 63187-0694-60 | 60 TABLET, FILM COATED in 1 BOTTLE (63187-694-60) | 2016-04-01 | Active |
| 63187-0694-90 | 90 TABLET, FILM COATED in 1 BOTTLE (63187-694-90) | 2016-04-01 | Active |
You're viewing the smallest of 3 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
🚨 Boxed Warning ▾
WARNING: FETAL TOXICITY • When pregnancy is detected, discontinue valsartan and hydrochlorothiazide as soon as possible [see Warnings and Precautions (5.1) ]. • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus [see Warnings and Precautions (5.1) ]. • When pregnancy is detected, discontinue valsartan and hydrochlorothiazide as soon as possible. (5.1) • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. (5.1)
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Valsartan and hydrochlorothiazide tablets, USP are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including hydrochlorothiazide and the ARB class to which valsartan principally belongs.
There are no controlled trials demonstrating risk reduction with valsartan and hydrochlorothiazide tablets, USP. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than 1 drug to achieve blood pressure goals.
For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits.
The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality have also been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (e.g., patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.
Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Add-On Therapy Valsartan and hydrochlorothiazide tablets, USP may be used in patients whose blood pressure is not adequately controlled on monotherapy.
Replacement Therapy Valsartan and hydrochlorothiazide tablets, USP may be substituted for the titrated components. Initial Therapy Valsartan and hydrochlorothiazide tablets, USP may be used as initial therapy in patients who are likely to need multiple drugs to achieve blood pressure goals. The choice of valsartan and hydrochlorothiazide tablets, USP as initial therapy for hypertension should be based on an assessment of potential benefits and risks.
Patients with stage 2 hypertension are at a relatively high risk for cardiovascular events (such as strokes, heart attacks, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant. The decision to use a combination as initial therapy should be individualized and should be shaped by considerations such as baseline blood pressure, the target goal, and the incremental likelihood of achieving goal with a combination compared to monotherapy. Individual blood pressure goals may vary based upon the patient's risk.
Data from the high dose multifactorial trial [see Clinical Studies (14.1) ] provides estimates of the probability of reaching a target blood pressure with valsartan and hydr…
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • Dose once daily. Titrate as needed to a maximum dose of 320 mg/25 mg. (2) • May be used as add-on/switch therapy for patients not adequately controlled on any of the components (valsartan or hydrochlorothiazide). (2) • May be substituted for titrated components. (2.3)
2.1General Considerations The usual starting dose is valsartan and hydrochlorothiazide tablets 160 mg/12.5 mg once daily. The dosage can be increased after 1 to 2 weeks of therapy to a maximum of one 320 mg/25 mg tablet once daily as needed to control blood pressure [see Clinical Studies (14.2) ]. Maximum antihypertensive effects are attained within 2 to 4 weeks after a change in dose.
2.2Add-On Therapy A patient whose blood pressure is not adequately controlled with valsartan (or another ARB) alone or hydrochlorothiazide alone may be switched to combination therapy with valsartan and hydrochlorothiazide tablets. A patient who experiences dose-limiting adverse reactions on either component alone may be switched to valsartan and hydrochlorothiazide tablets containing a lower dose of that component in combination with the other to achieve similar blood pressure reductions. The clinical response to valsartan and hydrochlorothiazide tablets should be subsequently evaluated and if blood pressure remains uncontrolled after 3 to 4 weeks of therapy, the dose may be titrated up to a maximum of 320 mg/25 mg.
2.3Replacement Therapy Valsartan and hydrochlorothiazide tablets may be substituted for the titrated components.
2.4Initial Therapy Valsartan and hydrochlorothiazide tablets are not recommended as initial therapy in patients with intravascular volume depletion [see Warnings and Precautions (5.2) ] .
2.5Use with Other Antihypertensive Drugs Valsartan and hydrochlorothiazide tablets may be administered with other antihypertensive agents.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS • 80 mg/12.5 mg tablets are light orange colored, ovaloid, beveled edge, biconvex film-coated tablets debossed with ‘I’ on one side and ‘61’ on other side. • 160 mg/12.5 mg tablets are dark red colored, ovaloid, beveled edge, biconvex film-coated tablets debossed with ‘I’ on one side and ‘62’ on other side. • 160 mg/25 mg tablets are brown-orange colored, ovaloid, beveled edge, biconvex film-coated tablets debossed with ‘I’ on one side and ‘63’ on other side. • 320 mg/12.5 mg tablets are pink colored, oval shaped, beveled edge, biconvex film-coated tablets debossed with ‘I’ on one side and ‘64’ on other side. • 320 mg/25 mg tablets are yellow colored, oval shaped, beveled edge, biconvex film-coated tablets debossed with ‘I’ on one side and ‘65’ on other side.
Tablets (valsartan and hydrochlorothiazide): 80 mg/12.5 mg, 160 mg/12.5 mg, 160 mg/25 mg, 320 mg/12.5 mg, and 320 mg/25 mg. (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS Valsartan and hydrochlorothiazide tablets are contraindicated in patients who are hypersensitive to any component of this product. Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. Do not coadminister aliskiren with valsartan and hydrochlorothiazide tablets in patients with diabetes [see Drug Interactions (7) ] .
Anuria; Hypersensitivity to any sulfonamide-derived drugs or any component; Do not coadminister aliskiren with valsartan and hydrochlorothiazide tablets in patients with diabetes. (4)
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Hypotension: Correct volume depletion prior to initiation. (5.2) • Observe for signs of fluid or electrolyte imbalance. (5.9) • Monitor renal function and potassium in susceptible patients. (5.3, 5.7) • Exacerbation or activation of systemic lupus erythematosus. (5.5) • Acute angle-closure glaucoma. (5.8)
5.1Fetal Toxicity Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death.
When pregnancy is detected, discontinue valsartan and hydrochlorothiazide as soon as possible [see Use in Specific Populations (8.1) ] . Intrauterine exposure to thiazide diuretics is associated with fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.
5.2Hypotension in Volume- and/or Salt-Depleted Patients Excessive reduction of blood pressure was rarely seen (0.7%) in patients with uncomplicated hypertension treated with valsartan and hydrochlorothiazide in controlled trials. In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients receiving high doses of diuretics, symptomatic hypotension may occur. This condition should be corrected prior to administration of valsartan and hydrochlorothiazide, or the treatment should start under close medical supervision.
If hypotension occurs, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.
5.3Impaired Renal Function Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure on valsartan and hydrochlorothiazide. Monitor renal function periodically in these patients.
Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on valsartan and hydrochlorothiazide [see Drug Interactions (7) ] .
5.4Hypersensitivity Reaction Hydrochlorothiazide: Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such a history.
5.5Systemic Lupus Erythematosus Hydrochlorothiazide: Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.
5.6Lithium Interaction Increases in serum lithium concentrations and lithium toxicity have been reported with concomitant use of valsartan or thiazide diuretics. Monitor lithium levels in patients receiving valsartan and hydrochlorothiazide and lithium [see Drug Interactions (7) ] .
5.7Potassium Abnormalities Valsartan and Hydrochlorothiazide: In the controlled trials of various doses of valsartan and hydrochlorothiazide the incidence of hypertensive patients who developed hypokalemia (serum potassium <3.5 mEq/L) was 3%; the incidence of hyperkalemia (serum potassium >5.7 mEq/L) was 0.4%. Hydrochlorothiazide can cause hypokalemia and hyponatremia. Hypomagnesemia can result in hypokalemia which appears difficult to treat despite potassium repletion.
Drugs that inhibit the renin-angiotensin system can cause hyperkalemia. Monitor serum electrolytes periodically. If hypokalemia is accompanied by clinical…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The most common reasons for discontinuation of therapy with valsartan and hydrochlorothiazide were headache and dizziness. The only adverse experience that occurred in ≥2% of patients treated with valsartan and hydrochlorothiazide and at a higher incidence than placebo was nasopharyngitis (2.4% vs. 1.9%).
(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reactions rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates. Hypertension Valsartan and hydrochlorothiazide has been evaluated for safety in more than 5700 patients, including over 990 treated for over 6 months, and over 370 for over 1 year.
Adverse experiences have generally been mild and transient in nature and have only infrequently required discontinuation of therapy. The overall incidence of adverse reactions with valsartan and hydrochlorothiazide was comparable to placebo. The overall frequency of adverse reactions was neither dose-related nor related to gender, age, or race.
In controlled clinical trials, discontinuation of therapy due to side effects was required in 2.3% of valsartan and hydrochlorothiazide patients and 3.1% of placebo patients. The most common reasons for discontinuation of therapy with valsartan and hydrochlorothiazide were headache and dizziness. The only adverse reaction that occurred in controlled clinical trials in at least 2% of patients treated with valsartan and hydrochlorothiazide and at a higher incidence in valsartan and hydrochlorothiazide (n=4372) than placebo (n=262) patients was nasopharyngitis (2.4% vs.
1.9%). Dose-related orthostatic effects were seen in fewer than 1% of patients. In individual trials, a dose-related increase in the incidence of dizziness was observed in patients treated with valsartan and hydrochlorothiazide.
Other adverse reactions that have been reported with valsartan and hydrochlorothiazide (>0.2% of valsartan and hydrochlorothiazide patients in controlled clinical trials) without regard to causality, are listed below: Cardiovascular: Palpitations and tachycardia. Ear and Labyrinth: Tinnitus and vertigo. Gastrointestinal: Dyspepsia, diarrhea, flatulence, dry mouth, nausea, abdominal pain, abdominal pain upper, and vomiting.
General and Administration Site Conditions: Asthenia, chest pain, fatigue, peripheral edema and pyrexia. Infections and Infestations: Bronchitis, bronchitis acute, influenza, gastroenteritis, sinusitis, upper respiratory tract infection, and urinary tract infection. Investigations: Blood urea increased.
Musculoskeletal: Arthralgia, back pain, muscle cramps, myalgia, and pain in extremity. Nervous System: Dizziness postural, paresthesia, and somnolence. Psychiatric: Anxiety and insomnia.
Renal and Urinary: Pollakiuria. Reproductive System: Erectile dysfunction. Respiratory, Thoracic and Mediastinal: Dyspnea, cough, nasal congestion, pharyngolaryngeal pain, and sinus congestion.
Skin and Subcutaneous Tissue: Hyperhidrosis and rash. Vascular: Hypotension. Other reported reactions seen less frequently in clinical trials included abnormal vision, anaphylaxis, bronchospasm, constipation, depression, dehydration, decreased libido, dysuria, epistaxis, flushing, gout, increased appetite, muscle weakness, pharyngitis, pruritus, sunburn, syncope, and viral infection.
Initial Therapy - Hypertension In a clinical study in patients with severe hypertension (diastolic blood pressure ≥110 mmHg and systolic blood pressure ≥140 mmHg), the overall pattern of adverse reactions rep…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Valsartan and Hydrochlorothiazide: Lithium: Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists or thiazides. Monitor lithium levels in patients taking valsartan and hydrochlorothiazide. Valsartan: No clinically significant pharmacokinetic interactions were observed when valsartan was coadministered with amlodipine, atenolol, cimetidine, digoxin, furosemide, glyburide, hydrochlorothiazide, or indomethacin.
The valsartan-atenolol combination was more antihypertensive than either component, but it did not lower the heart rate more than atenolol alone. Coadministration of valsartan and warfarin did not change the pharmacokinetics of valsartan or the time-course of the anticoagulant properties of warfarin. CYP 450 Interactions: In vitro metabolism studies indicate that CYP 450 mediated drug interactions between valsartan and coadministered drugs are unlikely because of the low extent of metabolism [see Clinical Pharmacology (12.3) ] .
Transporters: The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1 and the hepatic efflux transporter MRP2. Coadministration of inhibitors of the uptake transporter (rifampin, cyclosporine) or efflux transporter (ritonavir) may increase the systemic exposure to valsartan. Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors): In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including valsartan, may result in deterioration of renal function, including possible acute renal failure.
These effects are usually reversible. Monitor renal function periodically in patients receiving valsartan and NSAID therapy. The antihypertensive effect of angiotensin II receptor antagonists, including valsartan may be attenuated by NSAIDs including selective COX-2 inhibitors.
Potassium: Concomitant use of valsartan with other agents that block the renin-angiotensin system, potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, salt substitutes containing potassium or other drugs that may increase potassium levels (e.g., heparin) may lead to increases in serum potassium and in heart failure patients to increases in serum creatinine. If comedication is considered necessary, monitoring of serum potassium is advisable. Dual Blockade of the Renin-Angiotensin System (RAS): Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy.
Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function, and electrolytes in patients on valsartan and hydrochlorothiazide and other agents that affect the RAS.
Do not coadminister aliskiren with valsartan and hydrochlorothiazide in patients with diabetes. Avoid use of aliskiren with valsartan and hydrochlorothiazide in patients with renal impairment (GFR <60 mL/min). Hydrochlorothiazide: When administered concurrently, the following drugs may interact with thiazide diuretics: Antidiabetic Drugs (oral agents and insulin) - Dosage adjustment of the antidiabetic drug may be required.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs and COX-2 selective inhibitors) - When valsartan 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. Carbamaze…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Nursing Mothers: Nursing or drug should be discontinued. (8.3)
8.1Pregnancy Teratogenic Effects Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death.
When pregnancy is detected, discontinue valsartan and hydrochlorothiazide as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents.
Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment.
If oligohydramnios is observed, discontinue valsartan and hydrochlorothiazide, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.
Closely observe infants with histories of in utero exposure to valsartan and hydrochlorothiazide for hypotension, oliguria, and hyperkalemia [see Use in Specific Populations (8.4) ] . Hydrochlorothiazide Thiazides can cross the placenta, and concentrations reached in the umbilical vein approach those in the maternal plasma. Hydrochlorothiazide, like other diuretics, can cause placental hypoperfusion.
It accumulates in the amniotic fluid, with reported concentrations up to 19 times higher than in umbilical vein plasma. Use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice or thrombocytopenia. Since they do not prevent or alter the course of EPH (Edema, Proteinuria, Hypertension) gestosis (pre-eclampsia), these drugs should not be used to treat hypertension in pregnant women.
The use of hydrochlorothiazide for other indications (e.g., heart disease) in pregnancy should be avoided.
8.3Nursing Mothers It is not known whether valsartan is excreted in human milk. Valsartan was excreted into the milk of lactating rats; however, animal breast milk drug levels may not accurately reflect human breast milk levels. Hydrochlorothiazide is excreted in human breast milk.
Because many drugs are excreted into human milk and because of the potential for adverse reactions in nursing infants from valsartan and hydrochlorothiazide, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
8.4Pediatric Use Safety and effectiveness of valsartan and hydrochlorothiazide in pediatric patients have not been established. Neonates with a history of in utero exposure to valsartan and hydrochlorothiazide: If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.
8.5Geriatric Use In the controlled clinical trials of valsartan and hydrochlorothiazide, 764 (17.5%) patients treated with valsartan and hydrochlorothiazide were ≥65 years and 118 (2.7%) were ≥75 years. No overall difference in the efficacy or safety of valsartan and hydrochlorothiazide was observed b…
🤰 Pregnancy ▾
8.1Pregnancy Teratogenic Effects Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death.
When pregnancy is detected, discontinue valsartan and hydrochlorothiazide as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents.
Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment.
If oligohydramnios is observed, discontinue valsartan and hydrochlorothiazide, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.
Closely observe infants with histories of in utero exposure to valsartan and hydrochlorothiazide for hypotension, oliguria, and hyperkalemia [see Use in Specific Populations (8.4) ] . Hydrochlorothiazide Thiazides can cross the placenta, and concentrations reached in the umbilical vein approach those in the maternal plasma. Hydrochlorothiazide, like other diuretics, can cause placental hypoperfusion.
It accumulates in the amniotic fluid, with reported concentrations up to 19 times higher than in umbilical vein plasma. Use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice or thrombocytopenia. Since they do not prevent or alter the course of EPH (Edema, Proteinuria, Hypertension) gestosis (pre-eclampsia), these drugs should not be used to treat hypertension in pregnant women.
The use of hydrochlorothiazide for other indications (e.g., heart disease) in pregnancy should be avoided.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of valsartan and hydrochlorothiazide in pediatric patients have not been established. Neonates with a history of in utero exposure to valsartan and hydrochlorothiazide: If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.
🧓 Geriatric Use ▾
8.5Geriatric Use In the controlled clinical trials of valsartan and hydrochlorothiazide, 764 (17.5%) patients treated with valsartan and hydrochlorothiazide were ≥65 years and 118 (2.7%) were ≥75 years. No overall difference in the efficacy or safety of valsartan and hydrochlorothiazide was observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
🆘 Overdosage ▾
10 OVERDOSAGE Valsartan and Hydrochlorothiazide: Limited data are available related to overdosage in humans. The most likely manifestations of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. Depressed level of consciousness, circulatory collapse and shock have been reported.
If symptomatic hypotension should occur, supportive treatment should be instituted. Valsartan is not removed from the plasma by dialysis. The degree to which hydrochlorothiazide is removed by hemodialysis has not been established.
The most common signs and symptoms observed in patients are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. In rats and marmosets, single oral doses of valsartan up to 1524 and 762 mg/kg in combination with hydrochlorothiazide at doses up to 476 and 238 mg/kg, respectively, were very well tolerated without any treatment-related effects.
These no adverse effect doses in rats and marmosets, respectively, represent 46.5 and 23 times the maximum recommended human dose (MRHD) of valsartan and 188 and 113 times the MRHD of hydrochlorothiazide on a mg/m 2 basis. (Calculations assume an oral dose of 320 mg/day valsartan in combination with 25 mg/day hydrochlorothiazide and a 60 kg patient.) Valsartan: Valsartan was without grossly observable adverse effects at single oral doses up to 2000 mg/kg in rats and up to 1000 mg/kg in marmosets, except for salivation and diarrhea in the rat and vomiting in the marmoset at the highest dose (60 and 31 times, respectively, the MRHD on a mg/m 2 basis).
(Calculations assume an oral dose of 320 mg/day and a 60 kg patient.) Hydrochlorothiazide: The oral LD 50 of hydrochlorothiazide is greater than 10 g/kg in both mice and rats, which represents 2027 and 4054 times, respectively, the MRHD on a mg/m 2 basis. (Calculations assume an oral dose of 25 mg/day and a 60 kg patient.)
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Valsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT 1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland.
Its action is therefore independent of the pathways for angiotensin II synthesis. There is also an AT 2 receptor found in many tissues, but AT 2 is not known to be associated with cardiovascular homeostasis. Valsartan has much greater affinity (about 20000-fold) for the AT 1 receptor than for the AT 2 receptor.
The primary metabolite of valsartan is essentially inactive with an affinity for the AT 1 receptor about one 200th that of valsartan itself. Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE.
Because valsartan does not inhibit ACE (kininase II) it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known. Valsartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.
Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of valsartan on blood pressure. Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts.
Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so coadministration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with these diuretics. The mechanism of the antihypertensive effect of thiazides is unknown.
12.2Pharmacodynamics Valsartan: Valsartan inhibits the pressor effect of angiotensin II infusions. An oral dose of 80 mg inhibits the pressor effect by about 80% at peak with approximately 30% inhibition persisting for 24 hours. No information on the effect of larger doses is available.
Removal of the negative feedback of angiotensin II causes a 2- to 3-fold rise in plasma renin and consequent rise in angiotensin II plasma concentration in hypertensive patients. Minimal decreases in plasma aldosterone were observed after administration of valsartan; very little effect on serum potassium was observed. Hydrochlorothiazide: After oral administration of hydrochlorothiazide, diuresis begins within 2 hours, peaks in about 4 hours and lasts about 6 to 12 hours.
Drug Interactions Hydrochlorothiazide: Alcohol, Barbiturates, or Narcotics: Potentiation of orthostatic hypotension may occur. Skeletal Muscle Relaxants: Possible increased responsiveness to muscle relaxants such as curare derivatives. Digitalis Glycosides: Thiazide-induced hypokalemia or hypomagnesemia may predispose the patient to digoxin toxicity.
12.3Pharmacokinetics Valsartan: Valsartan peak plasma concentration is reached 2 to 4 hours after dosing. Valsartan shows bi-exponential decay kinetics following intravenous administration, with an average elimination half-life of about 6 hours. Absolu…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Valsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT 1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland.
Its action is therefore independent of the pathways for angiotensin II synthesis. There is also an AT 2 receptor found in many tissues, but AT 2 is not known to be associated with cardiovascular homeostasis. Valsartan has much greater affinity (about 20000-fold) for the AT 1 receptor than for the AT 2 receptor.
The primary metabolite of valsartan is essentially inactive with an affinity for the AT 1 receptor about one 200th that of valsartan itself. Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE.
Because valsartan does not inhibit ACE (kininase II) it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known. Valsartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.
Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of valsartan on blood pressure. Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts.
Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so coadministration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with these diuretics. The mechanism of the antihypertensive effect of thiazides is unknown.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Valsartan and hydrochlorothiazide tablets, USP are available as non-scored tablets containing valsartan and hydrochlorothiazide 320 mg/12.5 mg are available as follows. Valsartan and Hydrochlorothiazide Tablets USP, 320 mg/25 mg are yellow colored, oval shaped, beveled edge, biconvex film-coated tablets debossed with 'I' on one side and '65' on other side. Bottles of 30 NDC 63187-694-30 Bottles of 60 NDC 63187-694-60 Bottles of 90 NDC 63187-694-90 Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature].
Protect from moisture and heat. Dispense in tight container (USP).
📋 Description ▾
11 DESCRIPTION Valsartan and hydrochlorothiazide is a combination of valsartan, an orally active, specific angiotensin II receptor blocker (ARB) acting on the AT 1 receptor subtype, and hydrochlorothiazide, a diuretic. Valsartan, a nonpeptide molecule, is chemically described as N -(1-oxopentyl)- N -[[2′-(1 H -tetrazol-5-yl)[1,1′-biphenyl]-4-yl]methyl]-L-Valine. Its molecular formula is C 24 H 29 N 5 O 3 , its molecular weight is 435.5, and its structural formula is: Valsartan USP is a white, fine hygroscopic powder.
It is soluble in ethanol and methanol and practically insoluble in water. Hydrochlorothiazide USP is a white or practically white, practically odorless, crystalline powder. It is slightly soluble in water; freely soluble in sodium hydroxide solution, in n -butylamine, and in dimethylformamide; sparingly soluble in methanol; and insoluble in ether, in chloroform, and in dilute mineral acids.
Hydrochlorothiazide is chemically described as 6-chloro-3,4-dihydro-2 H -1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Hydrochlorothiazide is a thiazide diuretic. Its molecular formula is C 7 H 8 ClN 3 O 4 S 2 , its molecular weight is 297.73, and its structural formula is: Valsartan and hydrochlorothiazide tablets, USP are formulated for oral administration to contain valsartan and hydrochlorothiazide, USP 80 mg/12.5 mg, 160 mg/12.5 mg, 160 mg/25 mg, 320 mg/12.5 mg, and 320 mg/25 mg.
The inactive ingredients of the tablets are colloidal silicon dioxide, crospovidone, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, sodium lauryl sulfate, talc, and titanium dioxide. In addition, the 80 mg/12.5 mg and 160 mg/12.5 mg contains iron oxide red and iron oxide yellow, the 160 mg/25 mg contains iron oxide black, iron oxide red, and iron oxide yellow, 320 mg/12.5 mg contains iron oxide black and iron oxide red, and the 320 mg/25 mg contains iron oxide yellow.
Valsartan Chemical Structure Hydrochlorothiazide Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Information for Patients Advise the patient to read the FDA-approved patient labeling (Patient Information) Pregnancy: Female patients of childbearing age should be told about the consequences of exposure to valsartan and hydrochlorothiazide during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible.
Symptomatic Hypotension: A patient receiving valsartan and hydrochlorothiazide should be cautioned that lightheadedness can occur, especially during the first days of therapy, and that it should be reported to the prescribing physician. The patients should be told that if syncope occurs, valsartan and hydrochlorothiazide should be discontinued until the physician has been consulted. All patients should be cautioned that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure, with the same consequences of lightheadedness and possible syncope.
Potassium Supplements: A patient receiving valsartan and hydrochlorothiazide should be told not to use potassium supplements or salt substitutes containing potassium without consulting the prescribing physician.