LISINOPRIL AND HYDROCHLOROTHIAZIDE  - lisinopril and hydrochlorothiazide tablet 
International Labs, Inc.

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LISINOPRIL AND HYDROCHLOROTHIAZIDE TABLETS USP - PACKAGE LABELS

DESCRIPTION




2 21 31 3 5 2

Picture of Lisinopril HCTZ - Chemical Structure  - 1





7 8 3 4 2

Picture of Lisinopril HCTZ - Chemical Structure  - 2









CLINICAL PHARMACOLOGY


Lisinopril-Hydrochlorothiazide






DOSAGE AND ADMINISTRATION




Lisinopril
Mechanism of Action


PRECAUTIONS


Pharmacokinetics and Metabolism
DOSAGE AND ADMINISTRATION

14

Pharmacodynamics
WARNINGS


PRECAUTIONS

Hydrochlorothiazide

INDICATIONS AND USAGE

Lisinopril and hydrochlorothiazide tablets are indicated for the treatment of hypertension. These fixed-dose combinations are not indicated for initial therapy (see DOSAGE AND ADMINISTRATION). In using lisinopril and hydrochlorothiazide tablets, consideration should be given to the fact that an angiotensin converting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen vascular disease, and that available data are insufficient to show that lisinopril does not have a similar risk. (See WARNINGS.) In considering use of lisinopril and hydrochlorothiazide tablets, it should be noted that Black patients receiving ACE inhibitors have been reported to have a higher incidence of angioedema compared to non-Blacks. (See WARNINGS, Head and Neck Angioedema.)

CONTRAINDICATIONS

Lisinopril and hydrochlorothiazide is contraindicated in patients who are hypersensitive to any component of this product and in patients with a history of angioedema related to previous treatment with an angiotensin
converting enzyme inhibitor and in patients with hereditary or idiopathic angioedema. Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. 

WARNINGS


General
Lisinopril
Anaphylactoid and Possibly Related Reactions:


Head and Neck Angioedema
Where there is involvement of the tongue, glottis or larynx, likely to cause airway obstruction, subcutaneous epinephrine solution 1:1000 (0.3 mL to 0.5 mL) and/or measures necessary to ensure a patent airway, should be promptly provided. (See ADVERSE REACTIONS.)
INDICATIONS AND USAGE and CONTRAINDICATIONS
Intestinal Angioedema
Anaphylactoid reactions during desensitization
Anaphylactoid reactions during membrane exposure:
Hypotension and Related Effects PRECAUTIONS, Drug Interactions ADVERSE REACTIONS PRECAUTIONS, Drug Interactions, ADVERSE REACTIONS DOSAGE AND ADMINISTRATION
Neutropenia/Agranulocytosis



Hepatic Failure:

Hydrochlorothiazide

PRECAUTIONS, Drug Interactions, Lisinopril Hydrochlorothiazide
Pregnancy
Lisinopril-Hydrochlorothiazide

Lisinopril, Fetal/Neonatal Morbidity and Mortality,
Lisinopril
Fetal/Neonatal Morbidity and Mortality
in utero
Hydrochlorothiazide

PRECAUTIONS


General
Lisinopril
Aortic Stenosis/Hypertrophic Cardiomyopathy

Impaired Renal Function: Evaluation of the hypertensive patient should always include assessment of renal function DOSAGE AND ADMINISTRATION
Hyperkalemia: Drug Interactions
Cough
Surgery/Anesthesia:

Hydrochlorothiazide
Drug Interactions, Agents Increasing Serum Potassium
Information for Patients
Angioedema
Symptomatic Hypotension:
Hyperkalemia
Neutropenia
Pregnancy:


Drug Interactions
Lisinopril
Hypotension — Patients on Diuretic Therapy:
WARNINGS DOSAGE AND ADMINISTRATION DOSAGE AND ADMINISTRATION
Non-steroidal Anti-inflammatory Agents Including Selective Cyclooxygenase-2 (COX-2) Inhibitors:
Other Agents:
Agents Increasing Serum Potassium:
Lithium:
Gold:
Hydrochlorothiazide

Alcohol, barbiturates, or narcotics
Antidiabetic drugs (oral agents and insulin) .
Other antihypertensive drugs



Cholestyramine and colestipol resins

Corticosteroids, ACTH
Pressor amines (e.g., norepinephrine)
Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine)
Lithium
Non-steroidal Anti-inflammatory Drugs
Carcinogenesis, Mutagenesis, Impairment of Fertility
Lisinopril-Hydrochlorothiazide
Salmonella typhimurium Escherichia coli in vitro in vitro in vivo
Lisinopril
in vitro in vitro in vivo
Hydrochlorothiazide
in vitro Salmonella typhimurium in vivo Drosophila in vitro Aspergillus nidulans
Pregnancy

Pregnancy Categories C and D WARNINGS, Pregnancy, Lisinopril, Fetal/Neonatal Morbidity and Mortality.
Nursing Mothers

14
Pediatric Use

Geriatric Use
DOSAGE AND ADMINISTRATION

ADVERSE REACTIONS


WARNINGS


Percent of Patients in Controlled Studies

Lisinopril-Hydrochlorothiazide (n=930)
Incidence(discontinuation)
Placebo(n=207)
Incidence
Dizziness
7.5(0.8)
1.9
Headache
5.2(0.3)
19
Cough
3.9(0.6)
1.0
Fatigue
3.7(0.4)
1.0
Orthostatic Effects
3.2(0.1)
1.0
Diarrhea
2.5(0.2)
2.4
Nausea
2.2(0.1)
2.4
Upper Respiratory Infection
2.2(0.0)
0.0
Muscle Cramps
2.0(0.4)
0.5
Asthenia
1.8(0.2)
1.0
Paresthesia
1.5(0.1)
0.0
Hypotension
1.4(0.1)
0.5
Vomiting
1.4(0.1)
0.5
Dyspepsia
1.3(0.0)
0.0
Rash
1.2(0.1)
0.5
Impotence
1.2(0.3)
0.0




Body as a Whole:
Cardiovascular Digestive: Musculoskeletal Nervous/Psychiatric Respiratory: Skin Special Senses Urogenital:
Angioedema WARNINGS
Hypotension:
WARNINGS
Cough: PRECAUTIONS, Cough.
Clinical Laboratory Test Findings
Serum Electrolytes PRECAUTIONS
Creatinine, Blood Urea Nitrogen PRECAUTIONS
Serum Uric Acid, Glucose, Magnesium, Cholesterol, Triglycerides and Calcium PRECAUTIONS
Hemoglobin and Hematocrit:
Liver Function Tests: WARNINGS, Hepatic Failure

Lisinopril Body as a Whole WARNINGS, Anaphylactoid and Possibly Related Reactions Cardiovascular: WARNINGS, Hypotension Digestive: WARNINGS Hepatic Failure Endocrine: Hematologic Metabolic Musculoskeletal Nervous System/Psychiatric Respiratory: Skin Special Senses Urogenital PRECAUTIONS DOSAGE AND ADMINISTRATION
Miscellaneous
Fetal/Neonatal Morbidity and Mortality: WARNINGS, Pregnancy, Lisinopril, Fetal/Neonatal
Morbidity and Mortality.
Hydrochlorothiazide
Body as a Whole:
Digestive: Hematologic Musculoskeletal Nervous System/Psychiatric WARNINGS); Skin Special Senses Hypersensitivity:

OVERDOSAGE

No specific information is available on the treatment of overdosage with lisinopril and hydrochlorothiazide. Treatment is symptomatic and supportive. Therapy with lisinopril and hydrochlorothiazide should be discontinued and the patient observed closely. Suggested measures include induction of emesis and/ or gastric lavage, and correction of dehydration, electrolyte imbalance and hypotension by established procedures.
Lisinopril
Following a single oral dose of 20 mg/kg, no lethality occurred in rats and death occurred in one of 20 mice receiving the same dose. The most likely manifestation of overdosage would be hypotension, for which the usual treatment would be intravenous infusion of normal saline solution. Lisinopril can be removed by hemodialysis. (See WARNINGS, Anaphylactoid reactions during membrane exposure.)
Hydrochlorothiazide
Oral administration of a single oral dose of 10 mg/kg to mice and rats was not lethal. 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.

DOSAGE AND ADMINISTRATION

Lisinopril is an effective treatment of hypertension in once-daily doses of 10 to 80 mg, while hydrochlorothiazide is effective in doses of 12.5 to 50 mg. In clinical trials of lisinopril/hydrochlorothiazide combination therapy using lisinopril doses of 10 to 80 mg and hydrochlorothiazide doses of 6.25 to 50 mg, the antihypertensive response rates generally increased with increasing dose of either component. The side effects (see WARNINGS) of lisinopril are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and doseindependent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of lisinopril and hydrochlorothiazide will be associated with both sets of dose-independent side effects, but addition of lisinopril in clinical trials blunted the hypokalemia normally seen with diuretics. To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.
Dose Titration Guided by Clinical Effect
A patient whose blood pressure is not adequately controlled with either lisinopril or hydrochlorothiazide monotherapy may be switched to lisinopril and hydrochlorothiazide tablets 10 mg/12.5 mg or lisinopril and hydrochlorothiazide tablets 20 mg/12.5 mg. Further increases of either or both components could depend on clinical response. The hydrochlorothiazide dose should generally not be increased until 2-3 weeks have elapsed. Patients whose blood pressures are adequately controlled with 25 mg of daily hydrochlorothiazide, but who experience significant potassium loss with this regimen, may achieve similar or greater blood pressure control with less potassium loss if they are switched to lisinopril and hydrochlorothiazide tablets 10 mg/12.5 mg. Dosage higher than lisinopril 80 mg and hydrochlorothiazide 50 mg should not be used.
Replacement Therapy
The combination may be substituted for the titrated individual components.
Use in Renal Impairment
The usual regimens of therapy with lisinopril and hydrochlorothiazide tablets need not be adjusted as long as the patient’s creatinine clearance is >30 mL/min/1.73 m2 (serum creatinine approximately ≤3 mg/dL or 265 μmol/L). In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so lisinopril and hydrochlorothiazide tablets are not recommended (see WARNINGS, Anaphylactoid reactions during membrane exposure).

HOW SUPPLIED








Storage



Lupin Limited



International Labs, Inc


Wal-Mart



LISINOPRIL AND HYDROCHLOROTHIAZIDE TABLETS USP 10 12.5 mg


Shellpak® Label

LB0010 - Lisinopril HCTZ Tablets USP 10 12.5 mg

LISINOPRIL AND HYDROCHLOROTHIAZIDE TABLETS USP 20 12.5 mg

Shellpak® Label

LB0011 Lisinopril HCTZ Tablets USP 20 12.5 mg

LISINOPRIL AND HYDROCHLOROTHIAZIDE TABLETS USP 20 25 mg

Shellpak® Label

LB0012 Lisinopril HCTZ Tablets USP 20 25 mg


LISINOPRIL AND HYDROCHLOROTHIAZIDE 
lisinopril and hydrochlorothiazide   tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 54458-993 (68180-518)
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
LISINOPRIL (LISINOPRIL) LISINOPRIL 10 mg
HYDROCHLOROTHIAZIDE (HYDROCHLOROTHIAZIDE) HYDROCHLOROTHIAZIDE 13 mg
Inactive Ingredients
Ingredient Name Strength
ANHYDROUS DIBASIC CALCIUM PHOSPHATE  
MAGNESIUM STEARATE  
MANNITOL  
STARCH, CORN  
FD&C BLUE NO. 2  
Product Characteristics
Color blue Score no score
Shape HEXAGON (6 sided) Size 7mm
Flavor Imprint Code LL;B01
Contains     
Packaging
# NDC Package Description Multilevel Packaging
1 54458-993-09 30 TABLET In 1 BLISTER PACK None

Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA077912 12/15/2007

LISINOPRIL AND HYDROCHLOROTHIAZIDE 
lisinopril and hydrochlorothiazide   tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 54458-992 (68180-519)
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
LISINOPRIL (LISINOPRIL) LISINOPRIL 20 mg
HYDROCHLOROTHIAZIDE (HYDROCHLOROTHIAZIDE) HYDROCHLOROTHIAZIDE 13 mg
Inactive Ingredients
Ingredient Name Strength
FERRIC OXIDE YELLOW  
Product Characteristics
Color yellow Score no score
Shape ROUND Size 8mm
Flavor Imprint Code LL;B02
Contains     
Packaging
# NDC Package Description Multilevel Packaging
1 54458-992-10 30 TABLET In 1 BLISTER PACK None

Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA077912 12/15/2007

LISINOPRIL AND HYDROCHLOROTHIAZIDE 
lisinopril and hydrochlorothiazide   tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 54458-991 (68180-520)
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
LISINOPRIL (LISINOPRIL) LISINOPRIL 20 mg
HYDROCHLOROTHIAZIDE (HYDROCHLOROTHIAZIDE) HYDROCHLOROTHIAZIDE 25 mg
Inactive Ingredients
Ingredient Name Strength
FERRIC OXIDE YELLOW  
FERRIC OXIDE RED  
Product Characteristics
Color orange (peach) Score no score
Shape ROUND Size 8mm
Flavor Imprint Code LL;B03
Contains     
Packaging
# NDC Package Description Multilevel Packaging
1 54458-991-10 30 TABLET In 1 BLISTER PACK None

Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA077912 12/15/2007

Labeler - International Labs, Inc. (023569924)
Registrant - International Labs, Inc. (023569924)
Establishment
Name Address ID/FEI Operations
International Labs, Inc. 023569924 manufacture, relabel, repack
Revised: 04/2010 International Labs, Inc.