Losartan Potassium and Hydrochlorothiazide 100 mg; 12.5 mg Tablet, Film Coated, 30-count — NDC 46708-0449-30 package photo

Losartan Potassium and Hydrochlorothiazide 100 mg; 12.5 mg Tablet, Film Coated, 30-count

by Alembic Pharmaceuticals Limited · 30 TABLET, FILM COATED in 1 BOTTLE (46708-449-30)
NDC 46708-0449-30
🏷️ FDA NDC (as labeled) 46708-449-30 billing pads the product segment with a zero
This package
Contains30-count Pack sizes4 compare ↓
Also priced by: Part D plans $0.1658/unit — full pricing hub ↓
Rx only Generic On market Non-controlled
🗂️ Data synced Sep 17, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →
⚠️
Other active recalls for Losartan Potassium And Hydrochlorothiazide (different manufacturers) — 1 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · May 7, 2024 — Presence of foreign substance: plastic-like substance. (MACLEODS PHARMA USA, INC) · FDA recall D-0498-2024
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

🆔 Identity & classification

FDA NDC (as labeled) 46708-449-30
Product NDC 46708-449
11-digit billing NDC 46708044930
RxCUI 979464, 979468, 979471
UNII 0J48LPH2TH, 3ST302B24A
UPC 0346708448301, 0346708449308, 0346708450304
Application # ANDA091617
SPL Set ID bbf7e20d-dfc2-4115-8788-c0cac15a1148
Established class (EPC) Thiazide Diuretic
Physiologic effect Increased Diuresis
Chemical class Thiazides
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2016-05-23
Route ORAL
Dosage form TABLET, FILM COATED
Substance LOSARTAN POTASSIUM; HYDROCHLOROTHIAZIDE
TE code (Orange Book) AB · RLD · RS
Why two NDCs? The FDA registers this code as 46708-449-30 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 46708-0449-30. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏷️ RxNorm drug class

This medicine belongs to the Angiotensin 2 Receptor Blocker class.

Pharmacologic class Angiotensin 2 Receptor Blocker
Drug family (ATC) Angiotensin II receptor blockers (ARBs), plain
How it works Angiotensin 2 Receptor Antagonists
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerAlembic Pharmaceuticals Limited
Application holderALEMBIC PHARMACEUTICALS LTD
FDA applicationANDA091617 (ANDA)
Labeler code46708
First marketedMay 2016
Product typeHuman Prescription Drug
Portfolio502 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

📗 Our plain-language guide HelloPharmacist
  • It's working in two ways at once to lower your blood pressure. Losartan relaxes your blood vessels by blocking a hormone called angiotensin II that would otherwise tighten them. Hy...
  • What exactly is this medication doing for me?
  • You can take it with or without food — a meal won't significantly change how well it works. Picking a consistent time each day (morning is common) helps you remember it and keeps y...
  • Can I take this with food, and does it matter what time of day I take it?
📖 Read our full Hydrochlorothiazide / Losartan guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

💊 What it looks like

Color Yellow / White
ShapeTear
ImprintL145
Size14 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

🧪 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.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • 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.
  • UNII RFW2ET671P
    Hydroxypropyl cellulose is a plant-derived thickening agent made from cellulose. It acts as a binder to hold tablet ingredients together and as a film-former to coat tablets or control how fast the medicine releases.
  • UNII 3NXW29V3WO
    Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
  • 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.
  • 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.
  • 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.
  • 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.

7 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMedingredient 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

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 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 systemPer eachPer 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 $0.1658 $4.97 / 30 tablets
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Losartan Potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 00093-7369-10 Teva 1000 tablets $0.075 AB Availability likely
Losartan Potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 16714-0224-01 NorthStar 30 tablets $0.075 AB Availability likely
Losartan potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 33342-0051-07 Macleods 30 tablets $0.075 AB Availability likely
Losartan Potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 43547-0425-03 Solco 30 tablets $0.075 AB Availability likely
Hyzaar 100 mg/1; 12.5 mg 78206-0140-01 Organon 30 tablets $6.820 AB Availability likely
losartan potassium and hydrochlorothiazide 12.5 mg/1; 100 mg 29300-0191-01 Unichem 100 tablets AB FDA listed
Losartan Potassium And Hydrochlorothiazide 100 mg/1; 12.5 mg 31722-0756-10 Camber 1000 tablets AB FDA listed
Losartan Potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 42291-0503-90 AvKARE 90 tablets AB FDA listed
Losartan Potassium and Hydrochlorothiazide 100 mg/1; 12.5 mgthis 46708-0449-30 Alembic 30 tablets AB FDA listed
Losartan Potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 50090-1745-00 A-S 30 tablets AB FDA listed
Losartan Potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 50090-5960-00 A-S 30 tablets AB FDA listed
Losartan Potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 59746-0338-01 Jubilant 100 tablets AB FDA listed
Losartan Potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 62332-0049-10 Alembic 10 tablets AB FDA listed
Losartan Potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 63187-0727-30 Proficient 30 tablets AB FDA listed
Losartan Potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 63187-0918-30 Proficient 30 tablets AB FDA listed
Losartan Potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 63629-2431-01 Bryant 1000 tablets AB FDA listed
Losartan Potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 65862-0469-10 Aurobindo 10 tablets AB FDA listed
Losartan Potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 68071-4159-03 NuCare 30 tablets AB FDA listed
Losartan Potassium and Hydrochlorothiazide 12.5 mg/1; 100 mg 68180-0216-01 Lupin 100 tablets AB FDA listed
Losartan Potassium and Hydrochlorothiazide 12.5 mg/1; 100 mg 68788-8632-01 Preferred 100 tablets AB FDA listed
Losartan Potassium And Hydrochlorothiazide 100 mg/1; 12.5 mg 70010-0188-03 Granules 30 tablets FDA listed
Losartan Potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 70518-3398-00 REMEDYREPACK 90 tablets AB Discontinued
Losartan Potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 71335-2572-01 Bryant 30 tablets AB FDA listed
losartan potassium and hydrochlorothiazide 12.5 mg/1; 100 mg 71335-2662-01 Bryant 30 tablets AB FDA listed
losartan potassium and hydrochlorothiazide 12.5 mg/1; 100 mg 71335-2827-01 Bryant 90 tablets AB FDA listed
Losartan potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 71335-3048-01 Bryant 1000 tablets AB FDA listed
Losartan Potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 72162-1700-00 Bryant 1000 tablets AB FDA listed
Losartan Potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 72162-2315-00 Bryant 1000 tablets AB FDA listed
losartan potassium and hydrochlorothiazide 12.5 mg/1; 100 mg 72162-2461-00 Bryant 1000 tablets AB FDA listed
Losartan potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 72162-2492-00 Bryant 1000 tablets AB FDA listed
Losartan Potassium And Hydrochlorothiazide 100 mg/1; 12.5 mg 72189-0098-90 Direct_Rx 90 tablets AB FDA listed
Losartan Potassium And Hydrochlorothiazide 100 mg/1; 12.5 mg 72189-0167-30 Direct_Rx 30 tablets AB FDA listed
Losartan Potassium And Hydrochlorothiazide 100 mg/1; 12.5 mg 72189-0290-90 DirectRx 90 tablets AB FDA listed
Losartan Potassium And Hydrochlorothiazide 100 mg/1; 12.5 mg 72189-0327-90 Direct 90 tablets AB FDA listed
Losartan Potassium and Hydrochlorothiazide 100 mg/1; 12.5 mg 82804-0103-90 Proficient 90 tablets AB FDA listed
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2016
On the market since
May 2016
📍
2026
Currently FDA-listed
10 years listed
🔓
·
Generic on the market
this product is a generic
This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Losartan potassium and hydrochlorothiazide — the ingredient across all brands.

Top reported reactions

Nausea774
Fatigue688
Dizziness590
Headache563
Diarrhoea534
Dyspnoea512
Pain511

Reporter sex

0 reports

Serious outcomes

Death698
Disabling469
Life-threatening425
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 568 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
46708-0449-10 100 BLISTER PACK in 1 CARTON (46708-449-10) / 10 TABLET, FILM COATED in 1 BLISTER PACK 2016-05-23 Active
46708-0449-30 You're viewing this 30 TABLET, FILM COATED in 1 BOTTLE (46708-449-30) 2016-05-23 Active
46708-0449-90 90 TABLET, FILM COATED in 1 BOTTLE (46708-449-90) 2016-05-23 Active
46708-0449-91 1000 TABLET, FILM COATED in 1 BOTTLE (46708-449-91) 2016-05-23 Active

Pack size FAQ

What quantity is in NDC 46708-0449-30?
NDC 46708-0449-30 is a 30-count package — 30 tablet, film coated in 1 bottle.
What is the difference between NDC 46708-0449-30 and NDC 46708-0449-90?
Both are Losartan Potassium and Hydrochlorothiazide 100 mg; 12.5 mg Tablet, Film Coated — the drug itself is identical. NDC 46708-0449-30 is the 30-count package, while NDC 46708-0449-90 is the 90 tablets package.
What NDC number is used to bill for this package of Losartan Potassium and Hydrochlorothiazide 100 mg; 12.5 mg Tablet, Film Coated?
Bill NDC 46708-0449-30 — the 11-digit billing format is 46708044930. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

🧭 About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
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.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 46708-449-30, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 46708-0449-30, written without dashes as 46708044930. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 46708-0449-30, the first segment (46708) is the labeler code FDA assigned to Alembic Pharmaceuticals Limited; the middle segment (0449) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (30) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Alembic Pharmaceuticals Limited. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 3 other package presentations of this same product, including 10 tablets (46708-0449-10), 90 tablets (46708-0449-90), 1000 tablets (46708-0449-91). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Alembic Pharmaceuticals Limited is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 82 words

WARNING: FETAL TOXICITY When pregnancy is detected, discontinue losartan potassium and hydrochlorothiazide tablets as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus [see Warnings and Precautions (5.1)]. WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning.

When pregnancy is detected, discontinue losartan potassium and hydrochlorothiazide tablets as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. (5.1)

🎯 Indications and Usage ~2 min read

1 INDICATIONS AND USAGE Losartan potassium and hydrochlorothiazide tablets USP are a combination of losartan, an angiotensin II receptor blocker (ARB) and hydrochlorothiazide, a diuretic indicated for: · Treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. (1.1) · Reduction of the risk of stroke in patients with hypertension and left ventricular hypertrophy.

There is evidence that this benefit does not apply to Black patients. (1.2)

1.1Hypertension Losartan potassium and hydrochlorothiazide tablets USP are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure lowers the risk of fatal and non-fatal cardiovascular (CV) events, primarily strokes and myocardial infarction. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including losartan and hydrochlorothiazide.

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 also have 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 (for example, 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. This fixed dose combination is not indicated for initial therapy of hypertension, except when the hypertension is severe enough that the value of achieving prompt blood pressure control exceeds the risk of initiating combination therapy in these patients [see Clinical Studies (14) and Dosage and Administration (2.1)].

Losartan potassium and hydrochlorothiazide tablets USP may be administered with other antihypertensive agents.

1.2Hypertensive Patients with Left Ventricular Hypertrophy Losartan potassium and hydrochlorothiazide tablets USP are indicated to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy, but there is evidence that this benefit does not apply to Black patients. [See Use in Specific Populations (8.6), Clinical Pharmacology (12.3), and Dosage and Administration (2.5).]

⏱️ Dosage and Administration ~2 min read

2 DOSAGE AND ADMINISTRATION Hypertension · Usual starting dose: 50/12.5 mg once daily. (2.1) · Titrate as needed to a maximum dose of 100/25 mg. (2.1) Hypertensive Patients with Left Ventricular Hypertrophy · Not controlled on monotherapy: Initiate with 50/12.5 mg. Titrate as needed to a maximum of 100/25 mg. (2.2)

2.1Hypertension The usual starting dose of losartan potassium and hydrochlorothiazide tablet is 50/12.5 (losartan 50 mg/hydrochlorothiazide 12.5 mg) once daily. The dosage can be increased after 3 weeks of therapy to a maximum of 100/25 (losartan 100 mg/hydrochlorothiazide 25 mg) once daily as needed to control blood pressure [see Clinical Studies (14.2)]. Initiate a patient whose blood pressure is not adequately controlled with losartan 50 mg monotherapy with losartan potassium and hydrochlorothiazide tablet 50/12.5 once daily.

If blood pressure remains uncontrolled after about 3 weeks of therapy, the dosage may be increased to two tablets of losartan potassium and hydrochlorothiazide tablet 50/12.5 once daily or one tablet of 100/25 once daily. Initiate a patient whose blood pressure is not adequately controlled with losartan 100 mg monotherapy with losartan potassium and hydrochlorothiazide tablet 100/12.5 (losartan 100 mg/hydrochlorothiazide 12.5 mg) once daily. If blood pressure remains uncontrolled after about 3 weeks of therapy, increase the dose to two tablets of losartan potassium and hydrochlorothiazide tablet 50/12.5 once daily or one tablet of losartan potassium and hydrochlorothiazide tablet 100/25 once daily.

Initiate a patient whose blood pressure is inadequately controlled with hydrochlorothiazide 25 mg once daily, or is controlled but who experiences hypokalemia with this regimen, on losartan potassium and hydrochlorothiazide tablet 50/12.5 once daily, reducing the dose of hydrochlorothiazide without reducing the overall expected antihypertensive response. Evaluate the clinical response to losartan potassium and hydrochlorothiazide tablet 50/12.5 and, if blood pressure remains uncontrolled after about 3 weeks of therapy, increase the dose to two tablets of losartan potassium and hydrochlorothiazide tablet 50/12.5 once daily or one tablet of losartan potassium and hydrochlorothiazide tablet 100/25 once daily.

2.2Hypertensive Patients with Left Ventricular Hypertrophy In patients whose blood pressure is not adequately controlled on 50 mg losartan potassium, initiate treatment with losartan potassium and hydrochlorothiazide tablet 50/12.5. If additional blood pressure reduction is needed, increase the dose to losartan potassium and hydrochlorothiazide tablet 100/12.5, followed by losartan potassium and hydrochlorothiazide tablet 100/25. For further blood pressure reduction add other antihypertensives [see Clinical Studies (14)] .

💊 Dosage Forms and Strengths 91 words

3 DOSAGE FORMS AND STRENGTHS · 50 mg/12.5 mg are yellow coloured, tear drop shaped, biconvex film coated tablets debossed with ‘L146’ on one side and plain on other side. · 100 mg/12.5 mg are white coloured, oval shaped, biconvex film coated tablets debossed with ‘L144’ on one side and plain on other side. · 100 mg/25 mg are yellow coloured, tear drop shaped, biconvex film coated tablets debossed with ‘L145’ on one side and plain on other side. Tablets (losartan potassium/hydrochlorothiazide content): 50/12.5 mg; 100/12.5 mg; and 100/25 mg.

(3)

Contraindications 59 words

4 CONTRAINDICATIONS Losartan potassium and hydrochlorothiazide tablet is contraindicated: · In patients who are hypersensitive to any component of this product. · In patients with anuria · For coadministration with aliskiren in patients with diabetes · Hypersensitivity to any component of losartan potassium and hydrochlorothiazide tablets. (4) · Anuria. (4) · Coadministration with aliskiren in patients with diabetes. (4)

⚠️ Warnings and Cautions ~2 min read

5 WARNINGS AND PRECAUTIONS · Hypotension: Correct volume or salt depletion prior to administration of losartan potassium and hydrochlorothiazide tablets. (5.2) · Monitor renal function and potassium in susceptible patients. (5.3) · Observe for clinical signs of fluid or electrolyte imbalance. (5.5) · Acute angle-closure glaucoma. (5.6) · Exacerbation of systemic lupus erythematosus. (5.7)

5.1Fetal Toxicity 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 losartan potassium and hydrochlorothiazide tablets as soon as possible. Thiazides cross the placental barrier and appear in cord blood. Adverse reactions include fetal or neonatal jaundice, thrombocytopenia [see Use in Specific Populations (8.1)].

5.2Hypotension in Volume-or Salt-Depleted Patients In patients with an activated renin-angiotensin system, such as volume-or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of treatment with losartan potassium and hydrochlorothiazide tablets. Correct volume or salt depletion prior to administration of losartan potassium and hydrochlorothiazide tablets. Do not use losartan potassium and hydrochlorothiazide tablets as initial therapy in patients with intravascular volume depletion.

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 losartan potassium and hydrochlorothiazide tablets. Monitor renal function periodically in these patients.

Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on losartan potassium and hydrochlorothiazide tablets [see Drug Interactions (7.3) and Use in Specific Populations (8.8)] .

5.4Hypersensitivity 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.

5.5Electrolyte and Metabolic Effects In double-blind clinical trials of various doses of losartan potassium and hydrochlorothiazide, the incidence of hypertensive patients who developed hypokalemia (serum potassium <3.5 mEq/L) was 6.7% versus 3.5% for placebo; the incidence of hyperkalemia (serum potassium >5.7 mEq/L) was 0.4% versus 0% for placebo. Losartan potassium and hydrochlorothiazide tablets contain hydrochlorothiazide which can cause hypokalemia, hyponatremia and hypomagnesemia. Hypomagnesemia can result in hypokalemia which may be difficult to treat despite potassium repletion.

Losartan potassium and hydrochlorothiazide tablets also contain losartan which can cause hyperkalemia. Monitor serum electrolytes periodically [see Drug Interactions (7.1)] . Hydrochlorothiazide may alter glucose tolerance and raise serum levels of cholesterol and triglycerides.

Hyperuricemia may occur or frank gout may be precipitated in patients receiving thiazide therapy. Because losartan decreases uric acid, losartan in combination with hydrochlorothiazide attenuates the diuretic-induced hyperuricemia. Hydrochlorothiazide decreases urinary calcium excretion and may cause elevations of serum calcium.

Monitor calcium levels.

5.6Acute Myopia and Secondary Angle-Closure Glaucoma Hydrochlorothiazide, a sulfonamide, can cause…

🤒 Adverse Reactions ~2 min read

6 ADVERSE REACTIONS Most common adverse reactions (incidence ≥2% and greater than placebo) are dizziness, upper respiratory infection, cough, and back pain. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Losartan potassium-hydrochlorothiazide has been evaluated for safety in 858 patients treated for essential hypertension and 3889 patients treated for hypertension and left ventricular hypertrophy. Most adverse reactions have been mild and transient in nature and have not required discontinuation of therapy.

In controlled clinical trials, discontinuation of therapy due to clinical adverse events was required in only 2.8% and 2.3% of patients treated with the combination and placebo, respectively. In these double-blind controlled clinical trials, adverse reactions occurring in greater than 2% of subjects treated with losartan-hydrochlorothiazide and at a greater rate than placebo were: back pain (2.1% vs 0.6%), dizziness (5.7% vs 2.9%), and upper respiratory infection (6.1% vs 4.6%). The following additional adverse reactions have been reported in clinical trials with losartan potassium and hydrochlorothiazide tablets and/or the individual components: Blood and the lymphatic system disorders: Anemia, aplastic anemia, hemolytic anemia, leukopenia, agranulocytosis.

Metabolism and nutrition disorders: Anorexia, hyperglycemia, hyperuricemia, electrolyte imbalance including hyponatremia and hypokalemia. Psychiatric disorders: Insomnia, restlessness. Nervous system disorders: Dysgeusia, headache, migraine, paraesthesias.

Eye disorders: Xanthopsia, transient blurred vision. Cardiac disorders: Palpitation, tachycardia. Vascular disorders: Dose-related orthostatic effects, necrotizing angiitis (vasculitis, cutaneous vasculitis).

Respiratory, thoracic and mediastinal disorders: Nasal congestion, pharyngitis, sinus disorder, respiratory distress (including pneumonitis and pulmonary edema). Gastrointestinal disorders: Dyspepsia, abdominal pain, gastric irritation, cramping, diarrhea, constipation, nausea, vomiting, pancreatitis, sialoadenitis. Hepato-biliary disorders: Jaundice (intrahepatic cholestatic jaundice).

Skin and subcutaneous tissue disorders: Rash, pruritus, purpura, toxic epidermal necrolysis, urticaria, photosensitivity, cutaneous lupus erythematosus. Musculoskeletal and connective tissue disorders: Muscle cramps, muscle spasm, myalgia, arthralgia. Renal and urinary disorders: Glycosuria, renal dysfunction, interstitial nephritis, renal failure.

Reproductive system and breast disorders: Erectile dysfunction/impotence. General disorders and administration site conditions: Chest pain, edema/swelling, malaise, fever, weakness. Investigations: Liver function abnormalities.

Cough Persistent dry cough has been associated with ACE-inhibitor use and in practice can be a cause of discontinuation of ACE-inhibitor therapy. Two prospective, parallel-group, double-blind, randomized, controlled trials were conducted to assess the effects of losartan on the incidence of cough in hypertensive patients who had experienced cough while receiving ACE-inhibitor therapy. Patients who had typical ACE-inhibitor cough when challenged with lisinopril, whose cough disappeared on placebo, were randomized to losartan 50 mg, lisinopril 20 mg, or either placebo (one study, n=97) or 25 mg hydrochlorothiazide (n=135).

The double-blind treatment period lasted up to 8 weeks. The incidence of cough is shown in Table 1 below. Table 1: Study 1 * HCTZ Losartan Lisinopril Cough 25% 17% 69% Study 2 † Placebo Losartan Lisinopril Cough 35% 29% 62% * Demographics = (89% Caucasian, 64% female) † Demographics = (90% Caucasian, 51%…

🔄 Drug Interactions ~2 min read

7 DRUG INTERACTIONS · Agents increasing serum potassium: Risk of hyperkalemia. (7.1) · Lithium: Risk of lithium toxicity. (7.2) · Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): increased risk of renal impairment and reduced diuretic, natriuretic, and antihypertensive effects.

(7.3) · Dual inhibition of the renin-angiotensin system: increased risk of renal impairment, hypotension, syncope, and hyperkalemia. (7.4) · Antidiabetic drugs: dosage adjustment of antidiabetic may be required. (7.5) · Cholestyramine and colestipol: Reduced absorption of thiazides.

(7.5)

7.1Agents Increasing Serum Potassium Coadministration of losartan with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients.

7.2Lithium Increases in serum lithium concentrations and lithium toxicity have been reported with concomitant use of angiotensin II receptor antagonists or thiazide diuretics. Monitor lithium levels in patients receiving losartan potassium and hydrochlorothiazide tablets and lithium.

7.3Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors Losartan Potassium 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 losartan) may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving losartan and NSAID therapy.

The antihypertensive effect of angiotensin II receptor antagonists, including losartan, may be attenuated by NSAIDs, including selective COX-2 inhibitors. Hydrochlorothiazide The administration of a non-steroidal anti-inflammatory agent including a selective COX-2 inhibitor can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when losartan potassium and hydrochlorothiazide tablets and non-steroidal anti-inflammatory agents including selective COX-2 inhibitors are used concomitantly, observe closely to determine if the desired effect of the diuretic is obtained.

In patients receiving diuretic therapy, coadministration of NSAIDs with angiotensin receptor blockers, including losartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving hydrochlorothiazide, losartan, and NSAID therapy.

7.4Dual 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, syncope, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. The Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) trial enrolled 1448 patients with type 2 diabetes, elevated urinary-albumin-to-creatinine ratio, and decreased estimated glomerular filtration rate (GFR 30 to 89.9 mL/min), randomized them to lisinopril or placebo on a background of losartan therapy and followed them for a median of 2.2 years.

Patients receiving the combination of losartan and lisinopril did not obtain any additional benefit compared to monotherapy for the combined endpoint of decline in GFR, end-stage renal disease, or death, but experienced an increased incidence of hyperkalemia and acute kidney injury compared with the monotherapy group. Closely monitor blood pressure, renal function, and electrolytes in patients on losartan potassium and hydrochlorothiazide tablets and other agents that affect the RAS. Do not coadminister aliskiren with losartan potassium and hydrochlorothiazide tablets in patients with diabetes.

Avoid use of aliskiren with losartan potassium and hydrochlorothiazide tablets in patients with renal impairment (GFR <60 mL/…

👥 Use in Specific Populations ~3 min read

8 USE IN SPECIFIC POPULATIONS · Hepatic Impairment: Losartan potassium and hydrochlorothiazide tablet is not recommended for initial therapy, because the recommended starting dose is not available. (8.7)

8.1Pregnancy 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 losartan 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 losartan potassium and hydrochlorothiazide tablets, 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 losartan potassium and hydrochlorothiazide tablets for hypotension, oliguria, and hyperkalemia [see Use in Specific Populations (8.4)] . There was no evidence of teratogenicity in rats or rabbits treated with a maximum losartan potassium dose of 10 mg/kg/day in combination with 2.5 mg/kg/day of hydrochlorothiazide. At these dosages, respective exposures (AUCs) of losartan, its active metabolite, and hydrochlorothiazide in rabbits were approximately 5, 1.5, and 1 times those achieved in humans with 100 mg losartan in combination with 25 mg hydrochlorothiazide.

AUC values for losartan, its active metabolite and hydrochlorothiazide, extrapolated from data obtained with losartan administered to rats at a dose of 50 mg/kg/day in combination with 12.5 mg/kg/day of hydrochlorothiazide, were approximately 6, 2, and 2 times greater than those achieved in humans with 100 mg of losartan in combination with 25 mg of hydrochlorothiazide. Fetal toxicity in rats, as evidenced by a slight increase in supernumerary ribs, was observed when females were treated prior to and throughout gestation with 10 mg/kg/day losartan in combination with 2.5 mg/kg/day hydrochlorothiazide.

As also observed in studies with losartan alone, adverse fetal and neonatal effects, including decreased body weight, renal toxicity, and mortality, occurred when pregnant rats were treated during late gestation and/or lactation with 50 mg/kg/day losartan in combination with 12.5 mg/kg/day hydrochlorothiazide. Respective AUCs for losartan, its active metabolite and hydrochlorothiazide at these dosages in rats were approximately 35, 10 and 10 times greater than those achieved in humans with the administration of 100 mg of losartan in combination with 25 mg hydrochlorothiazide.

When hydrochlorothiazide was administered without losartan to pregnant mice and rats during their respective periods of major organogenesis, at doses up to 3000 and 1000 mg/kg/day, respectively, there was no evidence of harm to the fetus. Thiazides cross the placental barrier and appear in cord blood. There is a risk of fetal or neonatal jaundice, thrombocytopenia,…

🤰 Pregnancy ~3 min read

8.1Pregnancy 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 losartan 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 losartan potassium and hydrochlorothiazide tablets, 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 losartan potassium and hydrochlorothiazide tablets for hypotension, oliguria, and hyperkalemia [see Use in Specific Populations (8.4)] . There was no evidence of teratogenicity in rats or rabbits treated with a maximum losartan potassium dose of 10 mg/kg/day in combination with 2.5 mg/kg/day of hydrochlorothiazide. At these dosages, respective exposures (AUCs) of losartan, its active metabolite, and hydrochlorothiazide in rabbits were approximately 5, 1.5, and 1 times those achieved in humans with 100 mg losartan in combination with 25 mg hydrochlorothiazide.

AUC values for losartan, its active metabolite and hydrochlorothiazide, extrapolated from data obtained with losartan administered to rats at a dose of 50 mg/kg/day in combination with 12.5 mg/kg/day of hydrochlorothiazide, were approximately 6, 2, and 2 times greater than those achieved in humans with 100 mg of losartan in combination with 25 mg of hydrochlorothiazide. Fetal toxicity in rats, as evidenced by a slight increase in supernumerary ribs, was observed when females were treated prior to and throughout gestation with 10 mg/kg/day losartan in combination with 2.5 mg/kg/day hydrochlorothiazide.

As also observed in studies with losartan alone, adverse fetal and neonatal effects, including decreased body weight, renal toxicity, and mortality, occurred when pregnant rats were treated during late gestation and/or lactation with 50 mg/kg/day losartan in combination with 12.5 mg/kg/day hydrochlorothiazide. Respective AUCs for losartan, its active metabolite and hydrochlorothiazide at these dosages in rats were approximately 35, 10 and 10 times greater than those achieved in humans with the administration of 100 mg of losartan in combination with 25 mg hydrochlorothiazide.

When hydrochlorothiazide was administered without losartan to pregnant mice and rats during their respective periods of major organogenesis, at doses up to 3000 and 1000 mg/kg/day, respectively, there was no evidence of harm to the fetus. Thiazides cross the placental barrier and appear in cord blood. There is a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

🧒 Pediatric Use 66 words

8.4Pediatric Use Safety and effectiveness of losartan potassium and hydrochlorothiazide tablets in pediatric patients have not been established. Neonates with a history of in utero exposure to losartan potassium and hydrochlorothiazide tablets: If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function.

🧓 Geriatric Use 111 words

8.5Geriatric Use In a controlled clinical study for the reduction in the combined risk of cardiovascular death, stroke and myocardial infarction in hypertensive patients with left ventricular hypertrophy, 2857 patients (62%) were 65 years and over, while 808 patients (18%) were 75 years and over. In an effort to control blood pressure in this study, patients were coadministered losartan and hydrochlorothiazide 74% of the total time they were on study drug. No overall differences in effectiveness were observed between these patients and younger patients.

Adverse events were somewhat more frequent in the elderly compared to non-elderly patients for both the losartan-hydrochlorothiazide and the control groups [see Clinical Pharmacology (12.3)] .

🆘 Overdosage 149 words

10 OVERDOSAGE Losartan Potassium Significant lethality was observed in mice and rats after oral administration of 1000 mg/kg and 2000 mg/kg, respectively, about 44 and 170 times the maximum recommended human dose on a mg/m 2 basis. Limited data are available in regard to overdosage in humans. The most likely manifestation of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation.

If symptomatic hypotension should occur, supportive treatment should be instituted. Neither losartan nor its active metabolite can be removed by hemodialysis. Hydrochlorothiazide The oral LD 50 of hydrochlorothiazide is greater than 10 g/kg in both mice and rats.

The most common signs and symptoms observed 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. The degree to which hydrochlorothiazide is removed by hemodialysis has not been established.

🧬 Clinical Pharmacology ~3 min read

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Losartan Potassium Angiotensin II [formed from angiotensin I in a reaction catalyzed by angiotensin converting enzyme (ACE, kininase II)], is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues (e.g., vascular smooth muscle, adrenal gland).

There is also an AT 2 receptor found in many tissues but it is not known to be associated with cardiovascular homeostasis. Neither losartan nor its principal active metabolite exhibits any partial agonist activity at the AT 1 receptor, and both have much greater affinity (about 1000-fold) for the AT 1 receptor than for the AT 2 receptor. In vitro binding studies indicate that losartan is a reversible, competitive inhibitor of the AT 1 receptor.

The active metabolite is 10 to 40 times more potent by weight than losartan and appears to be a reversible, non-competitive inhibitor of the AT 1 receptor. Neither losartan nor its active metabolite inhibits ACE (kininase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin), nor do they bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation. Hydrochlorothiazide 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 Losartan Potassium Losartan inhibits the pressor effect of angiotensin II (as well as angiotensin I) infusions. A dose of 100 mg inhibits the pressor effect by about 85% at peak with 25 to 40% inhibition persisting for 24 hours. Removal of the negative feedback of angiotensin II causes a doubling to tripling in plasma renin activity and consequent rise in angiotensin II plasma concentration in hypertensive patients.

Losartan does not affect the response to bradykinin, whereas ACE inhibitors increase the response to bradykinin. Aldosterone plasma concentrations fall following losartan administration. In spite of the effect of losartan on aldosterone secretion, very little effect on serum potassium was observed.

The effect of losartan is substantially present within one week but in some studies the maximal effect occurred in 3 to 6 weeks. In long-term follow-up studies (without placebo control) the effect of losartan appeared to be maintained for up to a year. There is no apparent rebound effect after abrupt withdrawal of losartan.

There was essentially no change in average heart rate in losartan-treated patients in controlled trials. 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.

Other antihypertensive drugs — additive effect or potentiation. Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine) — possible increased responsiveness to the muscle relaxant. Corticosteroids, ACTH, or glycyrrhizin (found in liquorice) — intensified…

🧬 Mechanism of Action ~1 min read

12.1Mechanism of Action Losartan Potassium Angiotensin II [formed from angiotensin I in a reaction catalyzed by angiotensin converting enzyme (ACE, kininase II)], is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues (e.g., vascular smooth muscle, adrenal gland).

There is also an AT 2 receptor found in many tissues but it is not known to be associated with cardiovascular homeostasis. Neither losartan nor its principal active metabolite exhibits any partial agonist activity at the AT 1 receptor, and both have much greater affinity (about 1000-fold) for the AT 1 receptor than for the AT 2 receptor. In vitro binding studies indicate that losartan is a reversible, competitive inhibitor of the AT 1 receptor.

The active metabolite is 10 to 40 times more potent by weight than losartan and appears to be a reversible, non-competitive inhibitor of the AT 1 receptor. Neither losartan nor its active metabolite inhibits ACE (kininase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin), nor do they bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation. Hydrochlorothiazide 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 207 words

16 HOW SUPPLIED/STORAGE AND HANDLING Losartan Potassium and Hydrochlorothiazide Tablets USP are supplied as. Losartan Potassium and Hydrochlorothiazide Tablets USP 50 mg/12.5 mg: Yellow coloured, tear drop shaped, biconvex film coated tablets debossed with ‘L146’ on one side and plain on other side. NDC 46708-448-30 bottle of 30 tablets NDC 46708-448-90 bottle of 90 tablets NDC 46708-448-91 bottle of 1000 tablets NDC 46708-448-10 carton of 10 blisters of 10 tablets Losartan Potassium and Hydrochlorothiazide Tablets USP 100 mg/12.5 mg: White coloured, oval shaped, biconvex film coated tablets debossed with ‘L144’ on one side and plain on other side.

NDC 46708-449-30 bottle of 30 tablets NDC 46708-449-90 bottle of 90 tablets NDC 46708-449-91 bottle of 1000 tablets NDC 46708-449-10 carton of 10 blisters of 10 tablets Losartan Potassium and Hydrochlorothiazide Tablets USP 100 mg/25 mg: Yellow coloured, tear drop shaped, biconvex film coated tablets debossed with ‘L145’ on one side and plain on other side. NDC 46708-450-30 bottle of 30 tablets NDC 46708-450-90 bottle of 90 tablets NDC 46708-450-91 bottle of 1000 tablets NDC 46708-450-10 carton of 10 blisters of 10 tablets Storage Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].

Keep container tightly closed. Protect from light.

📋 Description ~2 min read

11 DESCRIPTION Losartan potassium and hydrochlorothiazide tablet USP 50 mg/12.5 mg, losartan potassium and hydrochlorothiazide tablet USP 100 mg/12.5 mg and losartan potassium and hydrochlorothiazide tablet USP 100 mg/25 mg combine an angiotensin II receptor blocker acting on the AT 1 receptor subtype and a diuretic, hydrochlorothiazide. Losartan potassium, a non-peptide molecule, is chemically described as 2-butyl-4-chloro-1-[ p- ( o -1 H- tetrazol-5-ylphenyl)benzyl]imidazole-5-methanol monopotassium salt. Its empirical formula is C 22 H 22 ClKN 6 O, and its structural formula is: Losartan potassium, USP is a white to off-white free-flowing crystalline powder with a molecular weight of 461.01.

It is freely soluble in water, soluble in alcohols, and slightly soluble in common organic solvents, such as acetonitrile and methyl ethyl ketone. Oxidation of the 5-hydroxymethyl group on the imidazole ring results in the active metabolite of losartan. Hydrochlorothiazide is 6-chloro-3,4-dihydro-2 H -1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide.

Its empirical formula is C 7 H 8 ClN 3 O 4 S 2 and its structural formula is: Hydrochlorothiazide, USP is a white, or practically white, crystalline powder with a molecular weight of 297.74, which is slightly soluble in water, but freely soluble in sodium hydroxide solution. Losartan potassium and hydrochlorothiazide tablets USP are available for oral administration in three tablet combinations of losartan USP and hydrochlorothiazide USP. Losartan potassium and hydrochlorothiazide tablet USP 50 mg/12.5 mg contain 50 mg of losartan potassium USP and 12.5 mg of hydrochlorothiazide USP.

Losartan potassium and hydrochlorothiazide tablet USP 100 mg/12.5 mg contain 100 mg of losartan potassium USP and 12.5 mg of hydrochlorothiazide USP. Losartan potassium and hydrochlorothiazide tablet USP 100 mg/25 mg contain 100 mg of losartan potassium USP and 25 mg of hydrochlorothiazide USP. Inactive ingredients are microcrystalline cellulose, lactose monohydrate, pregelatinized starch, magnesium stearate, hydroxypropyl cellulose, hypromellose, and titanium dioxide.

Losartan potassium and hydrochlorothiazide tablet USP 50 mg/12.5 mg and 100 mg/25 mg also contain D&C yellow No. 10 aluminum lake. Losartan potassium and hydrochlorothiazide tablet USP 50 mg/12.5 mg contain 4.24 mg (0.108 mEq) of potassium, losartan potassium and hydrochlorothiazide tablet USP 100 mg/12.5 mg contain 8.48 mg (0.216 mEq) of potassium, and losartan potassium and hydrochlorothiazide tablet USP 100 mg/25 mg contain 8.48 mg (0.216 mEq) of potassium.

USP dissolution test is pending. Structure Structure

💬 Information for Patients 196 words

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Pregnancy: Advise female patients of childbearing age about the consequences of exposure to losartan potassium and hydrochlorothiazide tablets during pregnancy. Discuss treatment options with women planning to become pregnant.

Tell patients to report pregnancies to their physicians as soon as possible [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)]. Symptomatic Hypotension: Advise patients that lightheadedness can occur, especially during the first days of therapy, and to report this symptom to a healthcare provider. Inform patients that dehydration from inadequate fluid intake, excessive perspiration, vomiting, or diarrhea may lead to an excessive fall in blood pressure.

If syncope occurs advise patients to contact their healthcare provider [see Warnings and Precautions (5.2)]. Po tassium Supplements: Advise patients not to use potassium supplements or salt substitutes containing potassium without consulting their healthcare provider [see Drug Interactions (7.1)]. Acute myopia and secondary angle-closure glaucoma: Advise patients to discontinue losartan potassium and hydrochlorothiazide tablets and seek immediate medical attention if they experience symptoms of Acute Myopia or Secondary Angle-Closure Glaucoma [see Warnings and Precautions (5.6)].

Alembic Pharmaceuticals Limited Manufactured in India Revised: 07/2025

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.