Lisinopril/Hydrochlorothiazide

Lisinopril/Hydrochlorothiazide
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2], Amr Marawan, M.D. [3]

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Black Box Warning

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Overview

Lisinopril/Hydrochlorothiazide is an Angiontensin converting enzyme inhibitor, Thiazide diuretic that is FDA approved for the {{{indicationType}}} of {{{indication}}}. There is a Black Box Warning for this drug as shown here. Common adverse reactions include hypotension (1.2% to 10.8% ), syncope (5.1% to 7% ), hyperkalemia (2.2% to 6.4% ), dizziness (5.4% to 18.9% ), headache (4.4% to 5.7% ), renal function tests abnormal and cough (3.5% ).

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Hypertension

• Initial dose (not initial therapy): lisinopril 10 mg/hydrochlorothiazide 12.5 mg PO gd or lisinopril 20 mg/hydrochlorothiazide 12.5 mg PO gd.

• Hydrochlorothiazide dosage should not be adjusted for 2-3 weeks, allow time for titration before increasing hydrochlorothiazide dose. lisinopril is effective at doses of 10 - 80 mg, and hydrochlorothiazide is effective at doses of 12.5 - 50 mg.

• Maintenance: MAX dose lisinopril 80 mg/hydrochlorothiazide 50 mg PO qd.

Off-Label Use and Dosage (Adult)

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Safety and effectiveness have not been established in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Contraindications

Lisinopril

Hydrochlorothiazide

• Hydrochlorothiazide is contraindicated in anuria. It is also contraindicated in patients who have previously demonstrated hypersensitivity to hydrochlorothiazide or other sulfonamide-derived drugs.

Warnings

{{{blackBoxWarningTitle}}} See full prescribing information for complete Boxed Warning. Condition Name: (Content)

Lisinopril

Hydrochlorothiazide

• Thiazides should be used with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.

• Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

• Sensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma.

• The possibility of exacerbation or activation of systemic lupus erythematosus has been reported.

• In general, lithium should not be given with diuretics

Adverse Reactions

Clinical Trials Experience

Lisinopril

X To be filled later X

Hydrochlorothiazide

General

• Chest pain, weakness, fever, viral infection.

Cardiovascular

• Orthostatic hypotension (seen in 1.8% of fosinopril sodium and hydrochlorothiazide patients and 0.3% of placebo patients; no patients discontinued therapy due to orthostatic hypotension), edema, flushing, rhythm disturbance, syncope.

Dermatologic

• Pruritus, rash.

Endocrine/Metabolic

• Sexual dysfunction, change in libido, breast mass.

Gastrointestinal

• Nausea/vomiting, diarrhea, dyspepsia/heartburn, abdominal pain, gastritis/ esophagitis.

Immunologic

• Angioedema (see WARNINGS: Head and Neck Angioedema and Intestinal Angioedema).

Musculoskeletal

• Myalgia/muscle cramps.

Neurologic/Psychiatric

• Somnolence, depression, numbness/paresthesia.

Respiratory

• Sinus congestion, pharyngitis, rhinitis.

Special Senses

• Tinnitus.

Urogenital

• Urinary tract infection, urinary frequency, dysuria.

Laboratory Test Abnormalities

• Serum electrolytes, uric acid, glucose, magnesium, cholesterol, triglycerides, and calcium (see PRECAUTIONS). Neutropenia.

• Antihypertensive monotherapy with fosinopril has been evaluated for safety in more than 1500 patients, of whom approximately 450 patients were treated for a year or more. The observed adverse events included events similar to those seen with fosinopril sodium and hydrochlorothiazide; in addition, the following others have also been reported with fosinopril:

Cardiovascular

• Angina, myocardial infarction, cerebrovascular accident, hypertensive crisis, hypotension, claudication.

Dermatologic

• Urticaria, photosensitivity.

Endocrine/Metabolic

• Gout.

Gastrointestinal

• Pancreatitis, hepatitis, dysphagia, abdominal distention, flatulence, appetite/weight change, dry mouth.

Hematologic

• Lymphadenopathy.

Musculoskeletal

• Arthralgia.

Neurologic/Psychiatric

• Memory disturbance, tremor, confusion, mood change, sleep disturbance.

Respiratory

• Bronchospasm, laryngitis/hoarseness, epistaxis, and (in two patients) a symptom-complex of cough, bronchospasm, and eosinophilia.

Special Senses

• Vision disturbance, taste disturbance, eye irritation.

Urogenital

• Renal insufficiency.

Laboratory Test Abnormalities

• Elevations (usually transient and minor) of BUN and creatinine have been observed, but these have not been more frequent than in parallel patients treated with placebo. The hemoglobin in fosinopril-treated patients generally decreases by an average of 0.1 g/dL, but this nonprogressive change has never been symptomatic. Leukopenia and eosinophilia have also been reported.

• Serum levels of liver function tests (transaminases, LDH, alkaline phosphatase and serum bilirubin) have occasionally been found to be elevated, and these elevations have lead to discontinuation of therapy in 0.7% of patients. Other risk factors for liver dysfunction have often been present in these cases; in any event the elevations generally have resolved after discontinuation of therapy with fosinopril.

Other Adverse Events Reported with ACE Inhibitors Other adverse effects reported with ACE inhibitors include cardiac arrest; pancytopenia, hemolytic anemia; aplastic anemia; thrombocytopenia; bullous pemphigus, exfoliative dermatitis; and a syndrome that may include one or more of arthralgia/arthritis, vasculitis, serositis, myalgia, fever, rash or other dermopathy, positive ANA titer, leukocytosis, eosinophilia, and elevated ESR. Hydrochlorothiazide has now been extensively prescribed for many years, but there has not been enough systematic collection of data to support an estimate of the frequency of the observed adverse reactions. Within organ-system groups, the reported reactions are listed here in decreasing order of severity, without regard to frequency.

Cardiovascular

• Orthostatic hypotension (may be potentiated by alcohol, barbiturates, or narcotics).

Gastrointestinal

• Pancreatitis, jaundice (intrahepatic cholestatic), sialadenitis, vomiting, diarrhea, cramping, nausea, gastric irritation, constipation, and anorexia.

Hematologic

• Aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia, and hemolytic anemia.

Immunologic

• Necrotizing angiitis, Stevens-Johnson syndrome, respiratory distress (including pneumonitis and pulmonary edema), anaphylactic reactions, purpura,urticaria, rash, and photosensitivity.

Metabolic

• Hyperglycemia, glycosuria, and hyperuricemia.

Musculoskeletal

• Muscle spasm.

Neurologic

• Vertigo, lightheadedness, transient blurred vision, headache, paresthesia, xanthopsia, weakness, and restlessness.

Postmarketing Experience

There is limited information regarding Lisinopril/Hydrochlorothiazide Postmarketing Experience in the drug label.

Drug Interactions

Lisinopril

X To be filled later X

Hydrochlorothiazide

• Thiazides may decrease arterial responsiveness to norepinephrine, but not enough to preclude effectiveness of the pressor agent for therapeutic use.

• Thiazides may increase the responsiveness to tubocurarine.

• The diuretic, natriuretic, and antihypertensive effects of thiazide diuretics may be reduced by concurrent administration of nonsteroidal anti-inflammatory agents; the effects (if any) of these agents on the antihypertensive effect of fosinopril sodium and hydrochlorothiazide have not been studied.

• By alkalinizing the urine,hydrochlorothiazide may decrease the effectiveness of methenamine.

• Cholestyramine and Colestipol Resins:Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43%, respectively.

• Hydrochlorothiazide: Under the auspices of the National Toxicology Program, rats and mice received hydrochlorothiazide for two years at doses up to 100 (rats) and 600 (mice) mg/kg/day. On a body weight basis, these highest doses were about 2400 times (mice) or 400 times (rats) the fosinopril sodium and hydrochlorothiazide dose of 12.5 mg, given to a 50 kg subject. On a body surface area basis, these doses are 226 times (mice) and 82 times (rats) the fosinopril sodium and hydrochlorothiazide dose. These studies uncovered no evidence of carcinogenicity in rats or female mice, but there was equivocal evidence of hepatocarcinogenicity in male mice.

• Hydrochlorothiazide was not genotoxic in in vitro assays using strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 of Salmonella typhimurium (Ames assay); in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations; or in in vivo assays using mouse germinal cell chromosomes; Chinese Hamster bone-marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Using concentrations of hydrochlorothiazide of 43 to 1300 mg/mL, positive test results were obtained in the in vitro CHO Sister Chromatid Exchange (clastogenicity) test and in the Mouse Lymphoma Cell (mutagenicity) assays. Using an unspecified concentration of hydrochlorothiazide, positive test results were also obtained in the Aspergillus nidulans nondisjunction assay.

• No adverse effects upon fertility were seen when rats and mice received dietary hydrochlorothiazide prior to mating and throughout gestation at doses up to 4 (rats) and 100 (mice) mg/kg/day. These doses are from 3.2 (body surface area basis in rats) to 400 (weight basis in mice) times greater than the dose received by a 50 kg human receiving 12.5 mg a day.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Lisinopril/Hydrochlorothiazide in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Lisinopril/Hydrochlorothiazide in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Lisinopril/Hydrochlorothiazide during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Lisinopril/Hydrochlorothiazide in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Lisinopril/Hydrochlorothiazide in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Lisinopril/Hydrochlorothiazide in geriatric settings.

Gender

There is no FDA guidance on the use of Lisinopril/Hydrochlorothiazide with respect to specific gender populations.

Race

There is no FDA guidance on the use of Lisinopril/Hydrochlorothiazide with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Lisinopril/Hydrochlorothiazide in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Lisinopril/Hydrochlorothiazide in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Lisinopril/Hydrochlorothiazide in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Lisinopril/Hydrochlorothiazide in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Lisinopril/Hydrochlorothiazide Administration in the drug label.

Monitoring

There is limited information regarding Lisinopril/Hydrochlorothiazide Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Lisinopril/Hydrochlorothiazide and IV administrations.

Overdosage

There is limited information regarding Lisinopril/Hydrochlorothiazide overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Lisinopril/Hydrochlorothiazide Pharmacology in the drug label.

Mechanism of Action

X To be filled later X

• 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, so coadministration of an ACE inhibitor tends to reverse the potassium loss associated with these diuretics.

• The mechanism of the antihypertensive effect of thiazides is unknown.

Structure

There is limited information regarding Lisinopril/Hydrochlorothiazide Structure in the drug label.

Pharmacodynamics

There is limited information regarding Lisinopril/Hydrochlorothiazide Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Lisinopril/Hydrochlorothiazide Pharmacokinetics in the drug label.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

X To be filled later X

Hydrochlorothiazide

• Under the auspices of the National Toxicology Program, rats and mice received hydrochlorothiazide for two years at doses up to 100 (rats) and 600 (mice) mg/kg/day. On a body weight basis, these highest doses were about 2400 times (mice) or 400 times (rats) the fosinopril sodium and hydrochlorothiazide dose of 12.5 mg, given to a 50 kg subject. On a body surface area basis, these doses are 226 times (mice) and 82 times (rats) the fosinopril sodium and hydrochlorothiazide dose. These studies uncovered no evidence of carcinogenicity in rats or female mice, but there was equivocal evidence of hepatocarcinogenicity in male mice.

• Hydrochlorothiazide was not genotoxic in in vitro assays using strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 of Salmonella typhimurium (Ames assay); in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations; or in in vivo assays using mouse germinal cell chromosomes; Chinese Hamster bone-marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Using concentrations of hydrochlorothiazide of 43 to 1300 mg/mL, positive test results were obtained in the in vitro CHO Sister Chromatid Exchange (clastogenicity) test and in the Mouse Lymphoma Cell (mutagenicity) assays. Using an unspecified concentration of hydrochlorothiazide, positive test results were also obtained in the Aspergillus nidulans nondisjunction assay.

• No adverse effects upon fertility were seen when rats and mice received dietary hydrochlorothiazide prior to mating and throughout gestation at doses up to 4 (rats) and 100 (mice) mg/kg/day. These doses are from 3.2 (body surface area basis in rats) to 400 (weight basis in mice) times greater than the dose received by a 50 kg human receiving 12.5 mg a day.

Clinical Studies

There is limited information regarding Lisinopril/Hydrochlorothiazide Clinical Studies in the drug label.

How Supplied

There is limited information regarding Lisinopril/Hydrochlorothiazide How Supplied in the drug label.

Storage

There is limited information regarding Lisinopril/Hydrochlorothiazide Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Lisinopril/Hydrochlorothiazide Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Lisinopril/Hydrochlorothiazide interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Lisinopril/Hydrochlorothiazide Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Lisinopril/Hydrochlorothiazide Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.