Hydrochlorothiazide / lisinopril

Treat hypertension to lower blood pressure. Use after an insufficient response to an individual component or as replacement for the titrated separate components. The selected label explicitly excludes initial fixed-combination therapy; it supplies no separate fixed-combination heart-failure, myocardial-infarction or pediatric indication.

For initiation of lisinopril in a patient already on a diuretic, the label advises stopping that diuretic for 2–3 days if possible. If it cannot be stopped, initiate lisinopril alone at 5 mg with supervised observation for ≥2 hours and until blood pressure is stable for ≥1 additional hour. This is not a fixed-tablet starting dose. The combination is not recommended when creatinine clearance is ≤30 mL/min; a loop diuretic is preferred in more severe impairment. No universal fixed-tablet maximum is inferred from the monotherapy or trial dose ranges.

Anuria; hypersensitivity to a component or other sulfonamide-derived medicines; prior ACE-inhibitor angioedema; hereditary or idiopathic angioedema. Do not combine with a neprilysin inhibitor or give within 36 hours of switching to/from sacubitril/valsartan. Do not coadminister aliskiren in patients with diabetes.

Drugs acting on the renin–angiotensin system can injure or kill the developing fetus. Discontinue as soon as pregnancy is detected. Later-pregnancy exposure can cause fetal renal failure, oligohydramnios, pulmonary/skeletal abnormalities and neonatal injury or death.

Common trial reactions included dizziness, headache, cough, fatigue and orthostatic effects; nausea, diarrhea and cramps also occurred. Serious component reactions include angioedema, renal dysfunction, blood-cell disorders, liver injury and severe skin/allergic reactions. Overdose may cause hypotension, dehydration and electrolyte depletion; obtain urgent medical/Poison Help advice for monitored supportive care. Lisinopril can be removed by hemodialysis, but membrane-associated reaction risk requires specialist management.

• Potassium supplements, potassium-sparing diuretics or potassium salt substitutes can produce dangerous hyperkalemia: use only with an assessed indication and frequent potassium monitoring.
• Generally avoid dual renin–angiotensin blockade: ARBs/ACE inhibitors/aliskiren increase hypotension, hyperkalemia and kidney-injury risk. Aliskiren is contraindicated with diabetes and should be avoided with GFR <60 mL/min.
• NSAIDs (including COX-2 inhibitors) can reduce BP/diuretic response and cause kidney deterioration, particularly with older age, dehydration or renal impairment; monitor renal function and response.
• Lithium generally should not be combined with a thiazide; both components increase toxicity risk. If a clinician elects coadministration, frequent lithium monitoring is required.
• Neprilysin inhibitors are contraindicated with ACE inhibitors; observe the 36-hour sacubitril/valsartan separation. mTOR inhibitors increase angioedema risk.

Alcohol, barbiturates, opioids and other antihypertensives can increase hypotension. Corticosteroids/ACTH increase electrolyte depletion, especially hypokalemia; low potassium heightens digoxin-related arrhythmia risk. HCTZ may require adjustment of diabetes treatment; cholestyramine/colestipol reduce HCTZ absorption. Nondepolarizing muscle-relaxant responsiveness may increase and pressor-amine response may decrease. Injectable gold with ACE inhibitors can cause flushing, nausea/vomiting and hypotension. Inform the anesthesia team; no universal resin-spacing regimen is inferred from this label.

Stop promptly when pregnancy is detected; discuss alternatives before a planned pregnancy. Infants exposed in utero need assessment for hypotension, oliguria and hyperkalemia. HCTZ enters human milk; human lisinopril milk data are unavailable in this label. Decide whether to stop nursing and/or the combination, considering maternal need and potential serious infant effects.

Safety and effectiveness of this fixed combination are not established in pediatric patients. Older adults require cautious dose selection and assessment of renal function and concomitant disease/medicines; the combination trials had insufficient numbers age ≥65 to establish age-related differences.

Assess renal function before treatment and monitor susceptible patients after initiation/titration. Creatinine clearance ≤30 mL/min: the fixed combination is not recommended; more severe impairment favors a loop diuretic. In liver dysfunction/progressive liver disease, use HCTZ cautiously because small electrolyte/fluid changes may cause hepatic coma. No fixed numeric hepatic-adjustment algorithm is provided.

Lisinopril inhibits conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion; ACE inhibition also affects bradykinin degradation. HCTZ increases sodium/chloride excretion through renal tubular action. The combination adds blood-pressure effects and may blunt thiazide-associated potassium loss.

Lisinopril

Mean absorption about 25%, unaffected by food; peak about 7 hours. Not metabolized, excreted unchanged in urine; effective accumulation half-life about 12 hours.

HCTZ

Not metabolized; at least 61% eliminated unchanged within 24 hours. Plasma half-life in measured studies: 5.6–14.8 hours.

HCTZ diuretic effect

Begins within about 2 hours, peaks around 4 hours and lasts about 6–12 hours.

Combination

Little or no effect on the separate agents’ bioavailability; renal impairment can prolong lisinopril exposure.

Assess blood pressure, orthostatic symptoms, renal function and serum electrolytes, especially potassium and sodium. Reassess after titration, dehydration or interacting medicines; use risk-based intervals rather than an invented universal schedule. Check glucose/uric acid when clinically appropriate and consider magnesium/calcium changes. Consider white counts with collagen vascular plus renal disease. Stop HCTZ before parathyroid-function testing as directed. Review skin protection and regular skin-cancer screening.

Report pregnancy immediately. For facial/tongue/throat swelling or breathing trouble, stop and obtain emergency care. New eye pain/vision loss needs urgent assessment. Report fainting, persistent lightheadedness, vomiting/diarrhea or dehydration and fever/sore throat. Avoid unsupervised potassium supplements/salt substitutes and review OTC NSAIDs. Rise carefully, protect skin from sunlight, and report persistent cough or jaundice. Verify tablet strength: this page consistently writes doses as lisinopril/HCTZ.

Ingredients / route

Lisinopril 10 mg + HCTZ 12.5 mg · oral tablet.

Appearance / imprint

Peach, round, biconvex, uncoated; 141 / ZESTORETIC.

Distributor

Almatica Pharma LLC.

Example NDC

52427-435-90 · bottle of 90.

U.S. status

Prescription fixed combination; no stock claim.

10/12.5 mg

Peach; 141 / ZESTORETIC; NDC 52427-435-90.

20/12.5 mg

White; 142 / ZESTORETIC; NDC 52427-436-90.

20/25 mg

Peach; 145 / ZESTORETIC; NDC 52427-437-90.

Order / scope

All strengths are lisinopril/HCTZ. Other manufacturers’ appearance and packages require their exact labels.

Store at controlled room temperature 20–25°C. Protect from light and humidity. Confirm strength and the exact dispensed package; do not identify an unfamiliar generic by brand appearance alone.