Lisinopril and hydrochlorothiazide tablet

Spl unclassified section

10 mg/12.5 mg, 20 mg/12.5 mg and 20 mg/25 mg

Rx only

Warning: fetal toxicity

  • When pregnancy is detected, discontinue lisinopril and hydrochlorothiazide as soon as possible.
  • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. See WARNINGS, Fetal Toxicity.

Description

Lisinopril and hydrochlorothiazide tablets USP combines an angiotensin converting enzyme inhibitor, lisinopril, and a diuretic, hydrochlorothiazide.

Lisinopril, a synthetic peptide derivative, is an oral long-acting angiotensin converting enzyme inhibitor. It is chemically described as ( S)-1-[ N 2 -(1-carboxy-3-phenylpropyl)-L-lysyl]-L-proline dihydrate. Its empirical formula is C 21H 31N 3O 52H2O and its structural formula is:

Lisinopril USP

Lisinopril is a white to off-white, crystalline powder, with a molecular weight of 441.52. It is soluble in water, sparingly soluble in methanol, and practically insoluble in ethanol.

Hydrochlorothiazide is 6-chloro-3,4-dihydro- 2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C 7H 8ClN 3O 4S 2and its structural formula is:

HCTZ USP

Hydrochlorothiazide is a white, or practically white, crystalline powder with a molecular weight of 297.73, which is slightly soluble in water, but freely soluble in sodium hydroxide solution.

Lisinopril and hydrochlorothiazide tablets are available for oral use in three tablet combinations of lisinopril with hydrochlorothiazide: lisinopril and hydrochlorothiazide tablets USP, 10 mg/12.5 mg, containing 10 mg lisinopril and 12.5 mg hydrochlorothiazide, lisinopril and hydrochlorothiazide tablets USP, 20 mg/12.5 mg, containing 20 mg lisinopril and 12.5 mg hydrochlorothiazide and lisinopril and hydrochlorothiazide tablets USP, 20 mg/25 mg, containing 20 mg lisinopril and 25 mg hydrochlorothiazide.

Inactive ingredients are dibasic calcium phosphate, magnesium stearate, mannitol, pregelatinized starch and starch. Lisinopril and hydrochlorothiazide tablets USP, 10 mg/12.5 mg also contains FD&C Blue No. 2 Aluminum Lake. Lisinopril and hydrochlorothiazide tablets USP, 20 mg/12.5 mg also contains yellow iron oxide and lisinopril and hydrochlorothiazide tablets USP, 20 mg/25 mg also contain red iron oxide.

Clinical pharmacology

Indications and usage

Lisinopril and hydrochlorothiazide tablets USP 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 USP, 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 USP, 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

Precautions

Information for patients

Angioedema: Angioedema, including laryngeal edema, may occur at any time during treatment with angiotensin converting enzyme inhibitors, including lisinopril. Patients should be so advised and told to report immediately any signs or symptoms suggesting angioedema (swelling of face, extremities, eyes, lips, tongue, difficulty in swallowing or breathing) and to take no more drug until they have consulted with the prescribing physician.

Symptomatic Hypotension: Patients should be cautioned to report lightheadedness especially during the first few days of therapy. If actual syncope occurs, the patients should be told to discontinue the drug until they have consulted with the prescribing physician.

All patients should be cautioned that excessive perspiration and dehydration may lead to an excessive fall in blood pressure because of reduction in fluid volume. Other causes of volume depletion such as vomiting or diarrhea may also lead to a fall in blood pressure; patients should be advised to consult with their physician.

Hyperkalemia: Patients should be told not to use salt substitutes containing potassium without consulting their physician.

Neutropenia: Patients should be told to report promptly any indication of infection (e.g., sore throat, fever) which may be a sign of neutropenia.

Drug interactions

Nursing mothers

It is not known whether lisinopril is secreted in human milk. However, milk of lactating rats contains radioactivity following administration of 14C lisinopril. In another study, lisinopril was present in rat milk at levels similar to plasma levels in the dams. Thiazides do appear in human milk. Because of the potential for serious reactions in nursing infants from ACE inhibitors and hydrochlorothiazide, a decision should be made whether to discontinue nursing or to discontinue lisinopril and hydrochlorothiazide, taking into account the importance of the drug to the mother.

Pediatric use

Neonates with a history of in utero exposure to lisinopril and hydrochlorothiazide:

If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. Lisinopril, which crosses the placenta, has been removed from neonatal circulation by peritoneal dialysis with some clinical benefit, and theoretically may be removed by exchange transfusion, although there is no experience with the latter procedure.

Geriatric use

Clinical studies of lisinopril and hydrochlorothiazide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. In a multiple-dose pharmacokinetic study in elderly versus young hypertensive patients using the lisinopril/hydrochlorothiazide combination, area under the plasma concentration time curve (AUC) increased approximately 120% for lisinopril and approximately 80% for hydrochlorothiazide in older patients.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection. Evaluation of the hypertensive patient should always include assessment of renal function. (See DOSAGE AND ADMINISTRATION .)

Adverse reactions

Lisinopril and hydrochlorothiazide has been evaluated for safety in 930 patients, including 100 patients treated for 50 weeks or more.

In clinical trials with lisinopril and hydrochlorothiazide no adverse experiences peculiar to this combination drug have been observed. Adverse experiences that have occurred have been limited to those that have been previously reported with lisinopril or hydrochlorothiazide.

The most frequent clinical adverse experiences in controlled trials (including open label extensions) with any combination of lisinopril and hydrochlorothiazide were: dizziness (7.5 percent), headache (5.2 percent), cough (3.9 percent), fatigue (3.7 percent) and orthostatic effects (3.2 percent), all of which were more common than in placebo-treated patients. Generally, adverse experiences were mild and transient in nature; but see WARNINGS regarding angioedema and excessive hypotension or syncope. Discontinuation of therapy due to adverse effects was required in 4.4 percent of patients, principally because of dizziness, cough, fatigue and muscle cramps.

Adverse experiences occurring in greater than one percent of patients treated with lisinopril plus hydrochlorothiazide in controlled clinical trials are shown below.

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)
1.9
Cough
3.9(0.6)
1.0
Fatigue
3.7(0.4)
1.0
OrthostaticEffects
3.2(0.1)
1.0
Diarrhea
2.5(0.2)
2.4
Nausea
2.2(0.1)
2.4
UpperRespiratoryInfection
2.2(0.0)
0.0
MuscleCramps
2.0(0.4)
0.5
Asthenia
1.8(0.2)
1.0
Paresthesia
1.5(0.1)
0.0
Hypotension
1.4(0.3)
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

Clinical adverse experiences occurring in 0.3 to 1.0 percent of patients in controlled trials included: Body as a Whole:Chest pain, abdominal pain, syncope, chest discomfort, fever, trauma, virus infection. Cardiovascular:Palpitation, orthostatic hypotension. Digestive:Gastrointestinal cramps, dry mouth, constipation, heartburn. Musculoskeletal:Back pain, shoulder pain, knee pain, back strain, myalgia, foot pain. Nervous/Psychiatric:Decreased libido, vertigo, depression, somnolence. Respiratory:Common cold, nasal congestion, influenza, bronchitis, pharyngeal pain, dyspnea, pulmonary congestion, chronic sinusitis, allergic rhinitis, pharyngeal discomfort. Skin:Flushing, pruritus, skin inflammation, diaphoresis. Special Senses:Blurred vision, tinnitus, otalgia. Urogenital:Urinary tract infection.

Angioedema:Angioedema has been reported in patients receiving lisinopril and hydrochlorothiazide, with an incidence higher in Black than in non-Black patients. Angioedema associated with laryngeal edema may be fatal. If angioedema of the face, extremities, lips, tongue, glottis and/or larynx occurs, treatment with lisinopril and hydrochlorothiazide should be discontinued and appropriate therapy instituted immediately. In rare cases, intestinal angioedema has been reported with angiotensin converting enzyme inhibitors including lisinopril. (See WARNINGS .)

Hypotension:In clinical trials, adverse effects relating to hypotension occurred as follows: hypotension (1.4), orthostatic hypotension (0.5), other orthostatic effects (3.2). In addition syncope occurred in 0.8 percent of patients. (See WARNINGS .)

Cough:See PRECAUTIONS, Cough.

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.

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 dose-independent 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.

How supplied

Lisinopril and Hydrochlorothiazide Tablets USP, 10 mg/12.5 mg are blue, hexagonal tablets, with "LL" debossed on one side and "B01" on other side.

60760-063-90 BOTTLES OF 90

Lisinopril and Hydrochlorothiazide Tablets USP, 20 mg/12.5 mg are yellow, round tablets, with "LL" debossed on one side and "B02" on other side.

NDC 60760-064-90 BOTTLES OF 90

60760-064-30 BOTTLES OF 30

Lisinopril and Hydrochlorothiazide Tablets USP, 20 mg/25 mg are peach, round tablets, with "LL" debossed on one side and "B03" on other side.

NDC 60760-065-30 BOTTLES OF 30

60760-065-90 BOTTLES OF 90

Storage

Store at 20 to 25C (68 to 77F). [See USP Controlled Room Temperature]. Protect from excessive light and humidity.

Spl unclassified section

Manufactured for:

Lupin Pharmaceuticals, Inc.

Baltimore, Maryland 21202

United States

Spl unclassified section

Manufactured by:

Lupin Limited

Goa 403 722

INDIA

Or

Lupin Limited

Pithampur (M.P.) 454 775

INDIA

Revised: September 2012 ID#: 230599

Ingredients and appearance - Product information

Lisinopril and hydrochlorothiazide tablet- Lisinopril and hydrochlorothiazide

Product information

Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC: 60760-063
Route of Administration Oral

Active Ingredient/Active Moiety

Ingredient Name Strength
Hydrochlorothiazide ( UNII: 0J48LPH2TH)( Hydrochlorothiazide - UNII: 0J48LPH2TH ) 12.5 mgin 1
Lisinopril ( UNII: E7199S1YWR)( Lisinopril anhydrous - UNII: 7Q3P4BS2FD ) 10 mgin 1

Inactive Ingredients

Ingredient Name Code
Anhydrous dibasic calcium phosphate ( UNII: L11K75P92J)
Fd&c blue no. 2 ( UNII: L06K8R7DQK)
Mannitol ( UNII: 3OWL53L36A)
Starch, corn ( UNII: O8232NY3SJ)
Magnesium stearate ( UNII: 70097M6I30)

Product Characteristics

Color blue Shape HEXAGON (6 sided)
Size 7 mm Score 1
Imprint Code LL;B01

Packaging

# Item Code Package Description Marketing Start Date
1 NDC: 60760-063-30 30 in 1 BOTTLE, PLASTIC 2013/05/16
2 NDC: 60760-063-90 90 in 1 BOTTLE, PLASTIC 2013/05/16

Marketing Information

Marketing Category Application Number or Monograph Citation Territorial Authority Marketing Start Date
ANDA ANDA077912 USA 2013/05/16

Lisinopril and hydrochlorothiazide tablet- Lisinopril and hydrochlorothiazide

Product information

Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC: 60760-064
Route of Administration Oral

Active Ingredient/Active Moiety

Ingredient Name Strength
Hydrochlorothiazide ( UNII: 0J48LPH2TH)( Hydrochlorothiazide - UNII: 0J48LPH2TH ) 12.5 mgin 1
Lisinopril ( UNII: E7199S1YWR)( Lisinopril anhydrous - UNII: 7Q3P4BS2FD ) 20 mgin 1

Inactive Ingredients

Ingredient Name Code
Anhydrous dibasic calcium phosphate ( UNII: L11K75P92J)
Ferric oxide yellow ( UNII: EX438O2MRT)
Mannitol ( UNII: 3OWL53L36A)
Starch, corn ( UNII: O8232NY3SJ)
Magnesium stearate ( UNII: 70097M6I30)

Product Characteristics

Color yellow Shape ROUND
Size 8 mm Score 1
Imprint Code LL;B02

Packaging

# Item Code Package Description Marketing Start Date
1 NDC: 60760-064-30 30 in 1 BOTTLE, PLASTIC 2013/05/16
2 NDC: 60760-064-90 90 in 1 BOTTLE, PLASTIC 2013/05/16

Marketing Information

Marketing Category Application Number or Monograph Citation Territorial Authority Marketing Start Date
ANDA ANDA077912 USA 2013/05/16

Lisinopril and hydrochlorothiazide tablet- Lisinopril and hydrochlorothiazide

Product information

Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC: 60760-065
Route of Administration Oral

Active Ingredient/Active Moiety

Ingredient Name Strength
Hydrochlorothiazide ( UNII: 0J48LPH2TH)( Hydrochlorothiazide - UNII: 0J48LPH2TH ) 25 mgin 1
Lisinopril ( UNII: E7199S1YWR)( Lisinopril anhydrous - UNII: 7Q3P4BS2FD ) 20 mgin 1

Inactive Ingredients

Ingredient Name Code
Anhydrous dibasic calcium phosphate ( UNII: L11K75P92J)
Ferric oxide red ( UNII: 1K09F3G675)
Mannitol ( UNII: 3OWL53L36A)
Starch, corn ( UNII: O8232NY3SJ)
Magnesium stearate ( UNII: 70097M6I30)

Product Characteristics

Color orange Shape ROUND
Size 8 mm Score 1
Imprint Code LL;B03

Packaging

# Item Code Package Description Marketing Start Date
1 NDC: 60760-065-30 30 in 1 BOTTLE, PLASTIC 2013/05/16
2 NDC: 60760-065-90 90 in 1 BOTTLE, PLASTIC 2013/05/16

Marketing Information

Marketing Category Application Number or Monograph Citation Territorial Authority Marketing Start Date
ANDA ANDA077912 USA 2013/05/16

Labeler - St Marys Medical Park Pharmacy( 063050751)

Establishment

Name ID/FEI Business Operations
St Marys Medical Park Pharmacy 063050751 relabel( 60760-063, 60760-064, 60760-065), repack( 60760-063, 60760-064, 60760-065)

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