Irbesartan and Hydrochlorothiazide

Aurobindo Pharma Limited

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use irbesartan and hydrochlorothiazide safely and effectively. See full prescribing information for irbesartan and hydrochlorothiazide tablets, USP. Irbesartan and Hydrochlorothiazide Tablets, USPInitial U.S. Approval: 1997RECENT MAJOR CHANGES(5.9)(5.1)(5.6)BOXED WARNINGWARNING: FETAL TOXICITY  See full prescribing information for complete boxed warning.   When pregnancy is detected, discontinue irbesartan 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 In patients not adequately controlled with monotherapy. (1) As initial therapy in patients likely to need multiple drugs to achieve their blood pressure goals. (1) DOSAGE AND ADMINISTRATIONGeneral Considerations Maximum effects within 2 to 4 weeks after dose change. (2.1) Renal Impairment: Not recommended for patients with severe renal impairment (creatinine clearance

FULL PRESCRIBING INFORMATION: CONTENTS*

• WARNING: FETAL TOXICITY
• 1 IRBESARTAN AND HYDROCHLOROTHIAZIDE INDICATIONS AND USAGE
• 2 IRBESARTAN AND HYDROCHLOROTHIAZIDE DOSAGE AND ADMINISTRATION
  • 2.1 General Considerations
  • 2.2 Add-On Therapy
  • 2.3 Replacement Therapy
  • 2.4 Initial Therapy
• 3 DOSAGE FORMS AND STRENGTHS
• 4 IRBESARTAN AND HYDROCHLOROTHIAZIDE CONTRAINDICATIONS
• 5 WARNINGS AND PRECAUTIONS
  • 5.1 Fetal Toxicity
  • 5.2 Hypotension in Volume- or Salt-Depleted Patients
  • 5.3 Hypersensitivity Reaction
  • 5.4 Systemic Lupus Erythematosus
  • 5.5 Lithium Interaction
  • 5.6 Electrolyte and Metabolic Imbalances
  • 5.7 Hepatic Impairment
  • 5.8 Impaired Renal Function
  • 5.9 Acute Myopia and Secondary Angle-Closure Glaucoma
• 6 IRBESARTAN AND HYDROCHLOROTHIAZIDE ADVERSE REACTIONS
  • 6.1 Clinical Trials Experience
  • 6.2 Postmarketing Experience
  • 6.3 Laboratory Abnormalities
• 7 DRUG INTERACTIONS
• 8 USE IN SPECIFIC POPULATIONS
  • 8.1 Pregnancy
  • 8.3 Nursing Mothers
  • 8.4 Pediatric Use
  • 8.5 Geriatric Use
• 10 OVERDOSAGE
• 11 IRBESARTAN AND HYDROCHLOROTHIAZIDE DESCRIPTION
• 12 CLINICAL PHARMACOLOGY
  • 12.1 Mechanism of Action
  • 12.2 Pharmacodynamics
  • 12.3 Pharmacokinetics
• 13 NONCLINICAL TOXICOLOGY
  • 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
  • 13.2 Animal Toxicology and/or Pharmacology
• 14 CLINICAL STUDIES
  • 14.1 Irbesartan Monotherapy
  • 14.2 Irbesartan-Hydrochlorothiazide
• 16 HOW SUPPLIED/STORAGE AND HANDLING
  • 16.1 How Supplied
  • 16.2 Storage
• 17 PATIENT COUNSELING INFORMATION
  • 17.1 Pregnancy
  • 17.2 Symptomatic Hypotension
• PACKAGE LABEL PRINCIPAL DISPLAY PANEL - 150 mg/12.5 mg (30 Tablet Bottle)
• PACKAGE LABEL PRINCIPAL DISPLAY PANEL - 300 mg/12.5 mg (30 Tablet Bottle)

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 General Considerations

2.2 Add-On Therapy

In patients not controlled on monotherapy with irbesartan or hydrochlorothiazide, the recommended doses of irbesartan and hydrochlorothiazide tablets, in order of increasing mean effect, are (irbesartan-hydrochlorothiazide) 150 mg/12.5 mg, 300 mg/12.5 mg, and 300 mg/25 mg. The largest incremental effect will likely be in the transition from monotherapy to 150 mg/12.5 mg [see Clinical Studies (14.2)].

2.3 Replacement Therapy

Irbesartan and hydrochlorothiazide tablets may be substituted for the titrated components.

2.4 Initial Therapy

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

• Irbesartan 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 co-administer aliskiren with irbesartan and hydrochlorothiazide tablets in patients with diabetes [see Drug Interactions (7)].

5 WARNINGS AND PRECAUTIONS

5.1 Fetal 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 irbesartan and hydrochlorothiazide as soon as possible [see Use in Specific Populations (8.1)].

Thiazides cross the placenta, and use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

5.2 Hypotension in Volume- or Salt-Depleted Patients

5.3 Hypersensitivity Reaction

5.4 Systemic Lupus Erythematosus

5.5 Lithium Interaction

5.6 Electrolyte and Metabolic Imbalances

Irbesartan-Hydrochlorothiazide

In double-blind clinical trials of various doses of irbesartan and hydrochlorothiazide, the incidence of hypertensive patients who developed hypokalemia (serum potassium <3.5 mEq/L) was 7.5% versus 6% for placebo; the incidence of hyperkalemia (serum potassium >5.7 mEq/L) was <1% versus 1.7% for placebo. No patient discontinued due to increases or decreases in serum potassium. On average, the combination of irbesartan and hydrochlorothiazide had no effect on serum potassium. Higher doses of irbesartan ameliorated the hypokalemic response to hydrochlorothiazide.

Based on experience with the use of other drugs that affect the renin-angiotensin system, concomitant use of potassium-sparing diuretics, potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium. Concurrent therapy with hydrochlorothiazide may reduce the frequency of this effect.
 

Hydrochlorothiazide

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.

Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.

Hydrochlorothiazide may alter glucose tolerance and raise serum levels of cholesterol and triglycerides.

5.7 Hepatic Impairment

5.8 Impaired Renal Function

5.9 Acute Myopia and Secondary Angle-Closure Glaucoma

Sulfonamide or sulfonamide derivative drugs, such as hydrochlorothiazide, can cause an idiosyncratic reaction, resulting in transient myopia and acute angle-closure glaucoma. Cases of acute angle-closure glaucoma have been reported with hydrochlorothiazide. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue drug intake as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

6.3 Laboratory Abnormalities

7 DRUG INTERACTIONS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 Animal Toxicology and/or Pharmacology

14 CLINICAL STUDIES

14.1 Irbesartan Monotherapy

14.2 Irbesartan-Hydrochlorothiazide

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

16.2 Storage

17 PATIENT COUNSELING INFORMATION

17.1 Pregnancy

Female patients of childbearing age should be told about the consequences of exposure to irbesartan and hydrochlorothiazide during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physician as soon as possible.

17.2 Symptomatic Hypotension

PACKAGE LABEL PRINCIPAL DISPLAY PANEL - 150 mg/12.5 mg (30 Tablet Bottle)

PACKAGE LABEL PRINCIPAL DISPLAY PANEL - 300 mg/12.5 mg (30 Tablet Bottle)