Irbesartan and Hydrochlorothiazide
Macleods Pharmaceuticals Limited
HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use Irbesartan and Hydrochlorothiazide Tablets USP safely and effectively. See full prescribing information for Irbesartan and Hydrochlorothiazide Tablets USP. Irbesartan and Hydrochlorothiazide Tablets USPInitial U.S. Approval: 1997 RECENT MAJOR CHANGES5.95.15.6BOXED WARNING5.15.1INDICATIONS AND USAGEIrbesartan and hydrochlorothiazide tablet USP is a combination of irbesartan, an angiotensin II receptor antagonist, and hydrochlorothiazide, a thiazide diuretic, indicated for hypertension: 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 2.12.15.8Hypertension 2.22.3DOSAGE FORMS AND STRENGTHS33CONTRAINDICATIONS4444WARNINGS AND PRECAUTIONS Hypotension: Correct volume-depletion prior to administration.(5.2). Impaired renal function (5.8). Thiazide diuretics may cause an exacerbation or activation of systemic lupus erythematosus (5.4). Acute myopia and secondary angle-closure glaucoma. (5.9) Side Effects6.1To report SUSPECTED ADVERSE REACTIONS, contact Macleods Pharma USA, Inc. at 1-888-943-3210or FDA at 1-800-FDA-1088 or www.fda.gov/medwatchDRUG INTERACTIONS77USE IN SPECIFIC POPULATIONS8.3
FULL PRESCRIBING INFORMATION: CONTENTS*
- BOXED WARNING
- 1 INDICATIONS & USAGE
- 2 DOSAGE & ADMINISTRATION
- 3 DOSAGE FORMS & STRENGTHS
- 4 IRBESARTAN AND HYDROCHLOROTHIAZIDE CONTRAINDICATIONS
- 5 WARNINGS AND PRECAUTIONS
- 6 IRBESARTAN AND HYDROCHLOROTHIAZIDE ADVERSE REACTIONS
- 7 DRUG INTERACTIONS
- 8 USE IN SPECIFIC POPULATIONS
- 10 OVERDOSAGE
- 11 IRBESARTAN AND HYDROCHLOROTHIAZIDE DESCRIPTION
- 12 CLINICAL PHARMACOLOGY
- 13 NONCLINICAL TOXICOLOGY
- 14 CLINICAL STUDIES
- 16 HOW SUPPLIED/STORAGE AND HANDLING
- 17 PATIENT COUNSELING INFORMATION
- PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FULL PRESCRIBING INFORMATION
1 INDICATIONS & USAGE
Clinical Studies (14.2)
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| Figure 1a: Probability of Achieving SBP <140 mmHg in Patients from Initial Therapy Studies V (Week 8) and VI (Week 7)* | Figure 1b: Probability of Achieving SBP <130 mmHg in Patients from Initial Therapy Studies V (Week 8) and VI (Week 7)* |
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| Figure 2a: Probability of Achieving DBP <90 mmHg in Patients from Initial Therapy Studies V (Week 8) and VI (Week 7)* | Figure 2b: Probability of Achieving DBP <80 mmHg in Patients from Initial Therapy Studies V (Week 8) and VI (Week 7)* |
2 DOSAGE & ADMINISTRATION
2.1 General Considerations
See Adverse Reactions (6)
Renal impairment.
Hepatic impairment.
2.2 Add-On Therapy
Clinical Studies (14.2)
2.3 Replacement Therapy
2.4 Initial Therapy
Clinical Studies (14.2)Warnings and Precautions (5.2)
3 DOSAGE FORMS & 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 tablets 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
Hydrochlorothiazide
5.4 Systemic Lupus Erythematosus
Hydrochlorothiazide
5.5 Lithium Interaction
Hydrochlorothiazide
Drug Interactions (7)
5.6 Electrolyte and Metabolic Imbalances
Irbesartan and hydrochlorothiazide
Hydrochlorothiazide
5.7 Hepatic Impairment
Hydrochlorothiazide
5.8 Impaired Renal Function
7
5.9 Acute Myopia and Secondary Angle-Closure Glaucoma
Sulfonamide or sulfonamide derivative drugs, such as hydrochlorothiazide, can cause 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
Irbesartan and hydrochlorothiazide
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Irbesartan/ HCTZ (n=898) (%) |
Placebo (n=236) (%) |
Irbesartan (n=400) (%) |
HCTZ (n=380) (%) |
|
Body as a Whole |
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|
|
|
|
Chest Pain |
2 |
1 |
2 |
2 |
|
Fatigue |
6 |
3 |
4 |
3 |
|
Influenza |
3 |
1 |
2 |
2 |
|
Cardiovascular |
|
|
|
|
|
Edema |
3 |
3 |
2 |
2 |
|
Tachycardia |
1 |
0 |
1 |
1 |
|
Gastrointestinal |
|
|
|
|
|
Abdominal Pain |
2 |
1 |
2 |
2 |
|
Dyspepsia/heartburn |
2 |
1 |
0 |
2 |
|
Nausea/vomiting |
3 |
0 |
2 |
2 |
|
Immunology |
|
|
|
|
|
Allergy |
1 |
0 |
1 |
1 |
|
Musculoskeletal |
|
|
|
|
|
Musculoskeletal Pain |
6 |
5 |
6 |
10 |
|
Nervous System |
|
|
|
|
|
Dizziness |
8 |
4 |
6 |
5 |
|
Dizziness Orthostatic |
1 |
0 |
1 |
1 |
|
Renal/Genitourinary |
|
|
|
|
|
Abnormality Urination |
2 |
1 |
1 |
2 |
The following adverse events were also reported at a rate of 1% or greater, but were as, or more, common in the placebo group: headache, sinus abnormality, cough, URI, pharyngitis, diarrhea, rhinitis, urinary tract infection, rash, anxiety/nervousness, and muscle cramp.
Adverse events occurred at about the same rates in men and women, older and younger patients, and black and non-black patients.
Adverse events in Studies V and VI were similar to those described above in Studies I through IV.
Irbesartan
Other adverse events that have been reported with irbesartan, without regard to causality, are listed below:
Body as a Whole: fever, chills, orthostatic effects, facial edema, upper extremity edema
Cardiovascular: flushing, hypertension, cardiac murmur, myocardial infarction, angina pectoris, hypotension, syncope, arrhythmic/conduction disorder, cardiorespiratory arrest, heart failure, hypertensive crisis
Dermatologic: pruritus, dermatitis, ecchymosis, erythema face, urticaria
Endocrine/Metabolic/Electrolyte Imbalances: sexual dysfunction, libido change, gout
Gastrointestinal: diarrhea, constipation, gastroenteritis, flatulence, abdominal distention
Musculoskeletal/Connective Tissue: musculoskeletal trauma, extremity swelling, muscle cramp, arthritis, muscle ache, musculoskeletal chest pain, joint stiffness, bursitis, muscle weakness
Nervous System: anxiety/nervousness, sleep disturbance, numbness, somnolence, vertigo, emotional disturbance, depression, paresthesia, tremor, transient ischemic attack, cerebrovascular accident
Renal/Genitourinary: prostate disorder
Respiratory: cough, upper respiratory infection, epistaxis, tracheobronchitis, congestion, pulmonary congestion, dyspnea, wheezing
Special Senses: vision disturbance, hearing abnormality, ear infection, ear pain, conjunctivitis
Hydrochlorothiazide
Other adverse events that have been reported with hydrochlorothiazide, without regard to causality, are listed below:
Body as a Whole: weakness
Digestive: pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation
Hematologic: aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia
Hypersensitivity: purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions
Metabolic: hyperglycemia, glycosuria, hyperuricemia
Musculoskeletal: muscle spasm
Nervous System/Psychiatric: restlessness
Renal: renal failure, renal dysfunction, interstitial nephritis
Skin: erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis
Special Senses
Initial Therapy
Clinical Studies (14.2).
6.2 Post-Marketing Experience
6.3 Laboratory Abnormalities
Creatinine, Blood Urea Nitrogen
Liver Function Tests
Serum ElectrolytesWarnings and Precautions (5.2, 5.6).
7 DRUG INTERACTIONS
Irbesartan
Clinical Pharmacology (12.3).
Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2-Inhibitors (COX-2 Inhibitors)
Dual Blockade of the Renin-Angiotensin System (RAS)
Hydrochlorothiazide
Alcohol, Barbiturates, or Narcotics
Antidiabetic Drugs (oral agents and insulin)
Other Antihypertensive Drugs
Cholestyramine and Colestipol Resins
Corticosteroids, ACTH
Pressor Amines (eg, Norepinephrine)
Skeletal Muscle Relaxants, Nondepolarizing (eg, Tubocurarine)
LithiumWarnings and Precautions (5.5)
Non-steroidal Anti-inflammatory Drugs
Carbamazepine
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category D
Use in Specific Populations (8.4)
Nonclinical Toxicology (13.2)
8.3 Nursing Mothers
8.4 Pediatric Use
Neonates with a history of in utero exposure to irbesartan and hydrochlorothiazide tablets:
8.5 Geriatric Use
Clinical Pharmacology (12.3) and Clinical Studies (14)
10 OVERDOSAGE
Irbesartan
Physicians’ Desk Reference (PDR)
2
Hydrochlorothiazide
50
11 DESCRIPTION
1
25286
78342
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Irbesartan
12
112
1
Hydrochlorothiazide
12.2 Pharmacodynamics
Irbesartan
Hydrochlorothiazide
12.3 Pharmacokinetics
Irbesartan
Hydrochlorothiazide
Metabolism and Elimination
Irbesartan
14
14
In vitro
Hydrochlorothiazide
Distribution
Irbesartan
1
Hydrochlorothiazide
Pediatric
Gender
Geriatric
max
Race
max
Renal Insufficiency
Warnings and Precautions (5.2)
Hepatic Insufficiency
Drug-Drug Interactions
In vitroin vitro
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis & Mutagenesis & Impairment Of Fertility
Irbesartan - hydrochlorothiazide
Irbesartan
0-24
0-24
Hydrochlorothiazide
in vitroSalmonella typhimuriumin vivoDrosophilain vitroAspergillus nidulans
13.2 Animal Pharmacology & OR Toxicology
Reproductive Toxicology Studies
14 CLINICAL STUDIES
14.1 Irbesartan Monotherapy
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14.2 Irbesartan and Hydrochlorothiazide
Initial Therapy
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
| Tablet Strength (irbesartan and hydrochlorothiazide) |
Film-Coated Tablet Color/Shape |
Tablet Markings |
Package Size |
NDC Code |
| 150 mg/12.5 mg |
peach, oval-shaped |
ML; 34 debossed on one side and plain on the reverse |
Bottles of 30 Bottles of 90 Bottles of 500 Blister pack of 30s (3 x 10s unit-dose blister) Blister pack of 90s (9 x 10s unit-dose blister) |
33342-057-07 33342-057-10 33342-057-15 33342-057-06 33342-057-39 |
| 300 mg/12.5 mg |
peach, oval-shaped |
ML; 33 debossed on one side and plain on the reverse |
Bottles of 30 Bottles of 90 Bottles of 500 Blister pack of 30s (3 x 10s unit-dose blister) Blister pack of 90s (9 x 10s unit-dose blister) |
33342-058-07 33342-058-10 33342-058-15 33342-058-06 33342-058-39 |
16.2 Storage
17 PATIENT COUNSELING INFORMATION
17.1 Pregnancy
17.2 Symptomatic Hypotension
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
REPRESENTATIVE PACKAGING
How Supplied
Irbesartan and HydrochlorothiazideIrbesartan and Hydrochlorothiazide TABLET, FILM COATED
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Irbesartan and HydrochlorothiazideIrbesartan and Hydrochlorothiazide TABLET, FILM COATED
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