lisinopril/hydrochlorothiazide (Rx)

Brand and Other Names:Zestoretic
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Dosing & Uses


Dosage Forms & Strengths



  • 10mg/12.5mg
  • 20mg/12.5mg
  • 20mg/25mg


10-80 mg lisinopril/6.25-50 mg hydrochlorothiazide PO qDay; titrate dose after 2-3 weeks of therapy based on clinical response; not to exceed 80 mg lisinopril or 50 mg hydrochlorothiazide per day

Dose considerations

Not for initial therapy; individualize dose; may substitute for individual components in patients currently maintained on both agents separately or not controlled with monotherapy

Safety and efficacy not established



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            Adverse Effects



            • Dizziness (5-12%)



            • Cough (4-9%)
            • Headache (4-6%)
            • Hyperkalemia (2-5%)
            • Diarrhea (3-4%)
            • Hypotension (1-4%)
            • Chest pain (3%)
            • Fatigue (3%)
            • Nausea/vomiting (2%)
            • Rash (1-2%)
            • Psoriasis (frequency unknown)


            • Hypotension
            • Anorexia
            • Epigastric distress
            • Hypokalemia
            • Phototoxicity

            Postmarketing Reports


            • Non-melanoma skin cancer


            Black Box Warnings

            Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system, causing oligohydramnios, which may result in fetal injury and/or death


            Hypersensitivity to ACE inhibitors, thiazides, or sulfonamides

            ACE-inhibitor induced angioedema, hereditary or idiopathic angioedema

            Coadministration of ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan

            Anuria or renal stenosis

            Coadministration with aliskiren in patients with diabetes mellitus


            Begin combination therapy only after failed monotherapy

            Severe renal impairment, hepatic impairment

            Risk of hypotension, especially with CHF

            Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with angiotensin-converting enzyme inhibitors

            If laryngeal stridor or angioedema of the face, tongue, or glottis occurs discontinue therapy and institute appropriate therapy immediately

            Patients receiving coadministration of ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g. temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema Intestinal angioedema has been reported in patients treated with ACE inhibitors

            Cholestatic jaundice may occur, which may progress to fulminant hepatic necrosis; discontinue if hepatic transaminase or jaundice occurs

            Dry hacking nonproductive cough may occur within few months of treatment; consider other causes of cough prior to discontinuation; cough may resolve within 1-4 weeks after discontinuation 0f therapy

            Hyperkalemia may occur with ACE inhibitors; risk factors include renal dysfunction, diabetes mellitus, and concomitant use of potassium sparing diuretics and potassium supplements; use cautiously if at all with these agents

            Thiazide diuretics may cause hypokalemia, hypochloremic alkalosis, hypomagnesemia, and hyponatremia

            Hydrochlorothiazide may precipitate gout in patients with familial predisposition to gout or chronic renal failure

            Symptomatic hypotension with or without syncope can occur with ACE inhibitors; mostly observed in volume depleted patients, correct volume depletion prior to initiation; monitor closely when initiating and increasing dosing

            Agranulocytosis, neutropenia, or leukopenia with myeloid hypoplasia reported with other ACE inhibitor; patients with both renal impairment and collagen disease are at increased risk of developing neutropenia; monitor CBC with differential in these patients

            Photosensitization may occur; instruct patients to protect skin from sun and undergo regular skin cancer screening

            Hydrochlorothiazide may cause acute transient myopia and acute angle-closure glaucoma that may occur within hours of initiating therapy; discontinue therapy immediately in patients with acute decreases in visual acuity or ocular pain; additional treatment may be needed if uncontrolled intraocular pressure persists; risk factors include history of sulfonamide or penicillin allergy

            Use caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia

            Closely observe patients with ischemic heart diseae or cerebrovascular disease as falling blood pressure may result in complications, including stroke and myocardial infarction; fluid replacement may restore blood pressure to resume therapy; discontinue if hypotension recurs

            Following bariatric surgery, diuretics should be avoided as dehydration and electrolyte disturbances may occur; diuretics may be resumed as indicated after oral fluid intake goals are reached

            Use hydrochlorothiazide with caution in patients with diabetes or at risk of diabetes; may see increase in glucose

            Use caution in patients collagen vascular disease, especially in patients with concomitant renal impairment

            Thiazide diuretics may decrease renal calcium excretion; consider avoiding use in patients with hypercalcemia

            Increased cholesterol and triglyceride levels reported with thiazides; use caution in patients with moderate to high cholesterol concentrations

            Pathologic changes in parathyroid glands with hypercalcemia and hypophosphatemia reported with prolonged use; discontinue prior to testing for parathyroid function

            Dual blockade of the renin-angiotensin-aldosterone system (ie, ARB plus an ACE inhibitor or aliskiren) in patients with established atherosclerotic disease or heart failure or with diabetes with end organ damage is associated with a higher frequency of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure), as compared with the use of a single renin-angiotensin-aldosterone system agent; limit dual blockade to individually defined cases, with close monitoring of renal function

            Neonates with history of in utero exposure: If oliguria or hypotension occurs, support of blood pressure and renal perfusion; exchange transfusions or dialysis may be required


            Pregnancy & Lactation

            Pregnancy category: D

            Lactation: Discontinue drug or do not nurse

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.





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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.