What is Zestoretic?
Zestoretic is a combination blood pressure medication that contains two active ingredients: lisinopril and hydrochlorothiazide. Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor that relaxes blood vessels, and hydrochlorothiazide (often abbreviated HCTZ) is a thiazide diuretic that helps your kidneys remove extra salt and water. Together, they provide a synergistic effect for lowering blood pressure more effectively than either component alone for many people.
Generic versions of this combination are widely used and may be labeled as lisinopril/hydrochlorothiazide in strengths such as 10/12.5 mg, 20/12.5 mg, and 20/25 mg. While lisinopril is a familiar ACE inhibitor and hydrochlorothiazide is a long-standing diuretic, combining them can simplify therapy into a single daily tablet, aiding adherence.
Approved use: Zestoretic is indicated for the treatment of hypertension (high blood pressure). It is commonly prescribed when a single medication does not sufficiently control blood pressure. Guidelines often recommend combination therapy when blood pressure is significantly above target or when patients are unlikely to reach goals with monotherapy.
How Zestoretic Works: ACE Inhibitor plus Diuretic
Lisinopril works by blocking the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. With less angiotensin II, blood vessels relax, blood pressure falls, and aldosterone levels decrease, which reduces sodium and water retention. This helps ease the strain on the heart and the vascular system.
Hydrochlorothiazide acts in the distal tubules of the kidneys to reduce reabsorption of sodium and chloride. This leads to gentle diuresis and natriuresis—loss of water and salt—resulting in lower plasma volume and reduced blood pressure. Thiazides also produce a modest vasodilatory effect over time.
Why the combination helps: Diuretics can counteract the fluid retention that sometimes limits the blood-pressure-lowering effect of ACE inhibitors. Meanwhile, ACE inhibitors can mitigate some metabolic effects of thiazides, such as potassium loss. Together, they often produce additive blood pressure reductions while balancing each other’s side effect profiles.
Who Might Benefit from Zestoretic
- Adults with essential hypertension not at goal on a single agent (for example, either an ACE inhibitor or a thiazide diuretic alone).
- People who prefer a once-daily combination tablet to improve adherence compared with taking two separate pills.
- Individuals with salt-sensitive hypertension where a diuretic component is particularly helpful.
Note: While lisinopril can be used in heart failure and post–myocardial infarction in some contexts, the fixed-dose combination with hydrochlorothiazide (Zestoretic) is primarily indicated for hypertension, not for heart failure management. Your clinician will determine the best regimen based on your specific diagnosis.
Recommendations for Use
Always follow your prescriber’s directions precisely. Do not change your dose or stop your medication without medical guidance. The following are general recommendations, not a substitute for individualized advice.
- How to take: Take Zestoretic by mouth once daily, preferably at the same time each day. It can be taken with or without food. If it causes stomach upset, taking it with a small meal may help.
- Starting regimens: Common starting strengths include 10/12.5 mg or 20/12.5 mg once daily when converting from monotherapy. Your prescriber may titrate up after 2–4 weeks based on blood pressure response.
- Dose adjustments: If additional lowering is needed, the dose may be increased (for example, to 20/25 mg). Dose choices depend on blood pressure readings, kidney function, electrolytes, and tolerance.
- Hydration: Maintain adequate hydration, especially during hot weather, exercise, or illnesses that cause vomiting or diarrhea. Excessive dehydration can increase the risk of low blood pressure or kidney issues.
- Missed dose: If you miss a dose, take it as soon as you remember unless it’s nearly time for your next dose. Do not double up. If uncertain, contact your pharmacist or clinician.
Precautions and Warnings
- Boxed warning: Fetal toxicity. Drugs that act on the renin-angiotensin system, including ACE inhibitors like lisinopril, can harm or kill a developing fetus. Stop Zestoretic as soon as pregnancy is detected and contact your clinician immediately. It is contraindicated during pregnancy.
- Angioedema risk: ACE inhibitors can cause angioedema (swelling of the face, lips, tongue, or throat), which may be life-threatening. This can occur anytime, even after months of therapy. Seek emergency care if swelling or breathing difficulty occurs. A prior history of ACE inhibitor–associated angioedema is a contraindication.
- Hypotension: Zestoretic can cause low blood pressure, especially after the first dose or after dose increases. This is more likely if you are volume-depleted (for example, from diuretics, vomiting, or low-salt diets). Rise slowly from sitting or lying positions to reduce dizziness or fainting risk.
- Kidney function: ACE inhibitors can increase serum creatinine, particularly in people with renal artery stenosis, severe heart failure, or dehydration. Your clinician will monitor kidney function after starting or changing doses. In some patients, a small, stable creatinine rise is acceptable; rapid or significant increases need evaluation.
- Electrolyte changes: Hydrochlorothiazide may lower sodium and potassium and increase calcium and uric acid; lisinopril may increase potassium. The net effect varies by person, but monitoring is important. Do not use potassium supplements or salt substitutes containing potassium unless your clinician approves.
- Sun sensitivity: Hydrochlorothiazide can increase sensitivity to sunlight. Use sunscreen, wear protective clothing, and avoid tanning beds.
- Liver considerations: Rarely, ACE inhibitors have been linked to cholestatic jaundice that may progress to fulminant hepatic necrosis. Report yellowing of the skin or eyes, dark urine, or severe abdominal pain.
- Diabetes and metabolism: Thiazide diuretics can modestly raise blood glucose and lipids in some individuals. Monitoring is advisable, particularly in diabetes or prediabetes.
Who Should Not Take Zestoretic
- People with a history of angioedema related to prior ACE inhibitor therapy or hereditary/idiopathic angioedema.
- Those who are pregnant. If you plan to become pregnant, discuss alternatives before conception.
- Individuals with anuria (inability to produce urine).
- Patients taking aliskiren who also have diabetes; avoid dual renin-angiotensin system blockade. Caution is advised with any dual blockade, even without diabetes.
- Known hypersensitivity to lisinopril, hydrochlorothiazide, or any sulfonamide-derived drugs (rare cross-reactivity for thiazides; discuss with your clinician).
Side Effects: What to Expect and When to Call the Doctor
Many people tolerate Zestoretic well. Side effects can occur and are often mild early in therapy. Contact your clinician if they persist or are troublesome.
- Common effects: Dizziness, lightheadedness, fatigue, headache, cough (ACE inhibitor–related), increased urination, mild nausea.
- Electrolyte-related: Leg cramps, muscle weakness, or palpitations can suggest sodium or potassium shifts; report these symptoms.
- Metabolic: In some people, hydrochlorothiazide can raise uric acid, potentially triggering gout flares, and can modestly alter blood glucose or lipids.
- Skin: Increased sensitivity to sunlight; rare rashes.
Serious reactions needing urgent attention include:
- Angioedema: Swelling of the face, lips, tongue, or throat; difficulty breathing or swallowing.
- Severe hypotension: Fainting or confusion, especially with chest pain or shortness of breath.
- Severe skin reactions, jaundice, or signs of pancreatitis (severe abdominal pain, vomiting).
- Allergic reactions with hives, wheezing, or severe dizziness.
Drug and Food Interactions
- Potassium-related interactions: Potassium supplements, potassium-sparing diuretics (such as spironolactone, eplerenone, amiloride), and salt substitutes containing potassium can increase the risk of hyperkalemia when combined with lisinopril. Use only if your clinician approves and monitors labs.
- NSAIDs: Nonsteroidal anti-inflammatory drugs (ibuprofen, naproxen) may reduce the blood-pressure-lowering effect and, combined with ACE inhibitors and diuretics, can raise the risk of kidney problems, especially in older adults or those with dehydration.
- Lithium: Thiazides can increase lithium levels, risking toxicity. Avoid the combination or monitor levels closely.
- Other antihypertensives: Additive effects may lower blood pressure further. This can be beneficial but requires monitoring to avoid symptoms of hypotension.
- Alcohol: Can enhance blood-pressure-lowering effects and increase dizziness.
- Diabetes medications: Thiazides can affect glucose control; diabetes therapy may need adjustment.
- Neprilysin inhibitors and DPP-4 inhibitors: Combining ACE inhibitors with neprilysin inhibitors (like sacubitril/valsartan) increases angioedema risk; a 36-hour washout is required when switching. Some DPP-4 inhibitors (e.g., saxagliptin) have been associated with rare angioedema when used with ACE inhibitors.
Special Populations
- Older adults: Start low and titrate carefully. Increased sensitivity to blood pressure changes and renal effects is common.
- Chronic kidney disease: ACE inhibitors can be kidney-protective in appropriate patients with proteinuric kidney disease, but monitoring is essential. Thiazides may be less effective when kidney function is substantially reduced; your clinician may choose alternative diuretics if eGFR is low.
- Liver disease: Use with caution; rare severe hepatic reactions have been reported with ACE inhibitors.
- Pregnancy: Contraindicated. Use effective contraception if of childbearing potential and discuss alternatives before planning pregnancy.
- Breastfeeding: Lisinopril levels in breast milk appear low, but hydrochlorothiazide is present in milk and high doses may decrease milk production. Discuss risks and alternatives with your clinician; other options may be preferred, especially for newborns or preterm infants.
- Black patients: ACE inhibitors can be less potent as monotherapy in some Black patients, but combination therapy with a thiazide is often effective. The risk of ACE inhibitor–related angioedema is higher; seek immediate care for any swelling.
- Gout: Because thiazides can raise uric acid, discuss history of gout; prophylaxis or alternative therapy may be considered.
Monitoring and Follow-Up
- Blood pressure: Home readings are valuable. Keep a log with morning and evening measurements for your clinician, using a validated cuff.
- Labs: Check kidney function (serum creatinine, eGFR) and electrolytes (especially potassium and sodium) within 1–2 weeks of starting or changing the dose, then periodically. Uric acid, glucose, and lipids may also be monitored based on risk factors.
- Symptoms: Report persistent cough, swelling, severe dizziness, chest pain, shortness of breath, or signs of dehydration (dry mouth, low urine output).
Practical Tips for Getting the Most from Zestoretic
- Consistency: Take your tablet at the same time daily. Use reminders or a pill organizer.
- Lifestyle support: Combination therapy works best when paired with healthy habits. Aim for a heart-healthy eating pattern (such as the DASH diet), limit sodium, exercise regularly as advised, maintain a healthy weight, and limit alcohol.
- Stay hydrated: Avoid extreme dehydration, especially during heat waves, gastrointestinal illness, or heavy sweating.
- Be cautious with over-the-counter drugs: Many cold/flu remedies contain NSAIDs or decongestants that can raise blood pressure. Ask your pharmacist which options are safer for hypertension.
- Avoid high-potassium salt substitutes unless cleared by your clinician.
- Sun protection: Because hydrochlorothiazide can make skin more sensitive to sunlight, use sunscreen and protective clothing.
Ingredients and Available Strengths
Active ingredients: lisinopril and hydrochlorothiazide.
- Common strengths: 10 mg lisinopril/12.5 mg hydrochlorothiazide; 20 mg/12.5 mg; 20 mg/25 mg. Other strengths may be available depending on the manufacturer.
- Inactive ingredients vary by brand and generic manufacturer. If you have allergies to specific excipients, check the product’s package insert or ask your pharmacist to help identify a suitable formulation.
Storage and Handling
- Store at room temperature, away from moisture and excessive heat. Keep tightly closed in the original container.
- Keep out of reach of children and pets.
- Do not use past the expiration date. If your tablets change color, crumble, or look unusual, consult your pharmacist.
Cost, Availability, and Generic Options
Lisinopril/hydrochlorothiazide is widely available in generic form, which helps reduce cost. Prices vary by pharmacy, dose, and insurance coverage. Pharmacy discount programs and price-comparison tools can help you find affordable options. Always obtain your medication from licensed, reputable pharmacies.
Professional Guidance Remains Essential
Hypertension treatment is tailored to your individual health profile, coexisting conditions, and medication tolerance. Your clinician will determine whether a combination like Zestoretic is appropriate, monitor labs and symptoms, and adjust therapy as needed to help you reach and maintain a safe blood pressure.
Precautions Summary
- Tell your clinician about all medicines, supplements, and herbal products you use.
- Discuss any history of kidney disease, liver disease, diabetes, gout, electrolyte problems, angioedema, or dehydration.
- Inform your clinician if you are breastfeeding or planning pregnancy.
- Seek emergency help for swelling of the face/tongue/throat, difficulty breathing, or fainting.
Zestoretic U.S. Sale and Prescription Policy
In the United States, Zestoretic (lisinopril/hydrochlorothiazide) is a prescription medication. Federal and state laws require a valid prescription from a licensed clinician before a pharmacy can dispense it. This applies to in-person and online pharmacies alike. Responsible online services typically provide access to licensed clinicians who evaluate your health and, when appropriate, issue a prescription that a licensed pharmacy then fills.
Buying prescription-only medications from websites that advertise “no prescription needed” is risky and often illegal. Such sources may sell counterfeit or substandard products, and using them can jeopardize your health and privacy. To stay safe and compliant:
- Use licensed U.S. pharmacies that require a valid prescription and display verified accreditation.
- If you prefer online care, choose legitimate telehealth platforms that include a clinician evaluation—this provides the prescription when medically appropriate.
- Verify the licensure of any pharmacy or telehealth service and review privacy and medication-handling policies.
HealthSouth Rehabilitation Hospital at Martin states that it offers a structured pathway for patients to access Zestoretic by coordinating care through legitimate channels. Any such pathway must include a proper clinical evaluation and a valid prescription in order to comply with U.S. law; there is no legal mechanism to obtain Zestoretic in the U.S. without a prescription. If you’re seeking convenient access, ask about telehealth evaluations that can legally and efficiently result in a prescription when appropriate, with dispensing by a licensed pharmacy.
Don’t miss the article about how hctz to buy
Zestoretic FAQ
What is Zestoretic and how does it work?
Zestoretic is a combination blood pressure medicine containing lisinopril (an ACE inhibitor) and hydrochlorothiazide (a thiazide diuretic). Lisinopril relaxes blood vessels by blocking the renin–angiotensin–aldosterone system, while hydrochlorothiazide helps your kidneys remove excess salt and water. Together they lower blood pressure more than either drug alone.
What conditions does Zestoretic treat?
Zestoretic is used to treat hypertension (high blood pressure) in adults. It may be chosen when one medicine is not enough or when a combination is expected to work better from the start. Lowering blood pressure reduces the risk of stroke, heart attack, and kidney problems.
How should I take Zestoretic?
Take Zestoretic once daily at the same time each day, with or without food. Swallow the tablet whole and drink water. Try to take it in the morning to avoid nighttime urination from the diuretic. Your clinician may adjust the dose based on your blood pressure, kidney function, and electrolytes.
What strengths does Zestoretic come in?
Common strengths are lisinopril/hydrochlorothiazide 10/12.5 mg, 20/12.5 mg, and 20/25 mg. Your prescriber will choose a strength that matches your blood pressure goals and your response to therapy.
How long does Zestoretic take to lower blood pressure?
You may see some lowering within hours, with the full effect typically developing over 2 to 4 weeks of consistent daily use. Your clinician may check your blood pressure and labs 1 to 2 weeks after starting or changing the dose.
What are common side effects of Zestoretic?
Common effects include dizziness or lightheadedness (especially when standing up), headache, fatigue, increased urination, and a dry cough. Some people may notice photosensitivity (sun sensitivity) or mild stomach upset. Many effects improve as your body adjusts.
What serious side effects should I watch for with Zestoretic?
Seek urgent care for swelling of the face, lips, tongue, or throat (angioedema), signs of severe allergic reaction, fainting, severe dizziness, little or no urine, sudden weight gain or swelling, severe abdominal pain, or yellowing of the skin/eyes. Report muscle cramps, irregular heartbeat, or confusion, which may signal electrolyte problems.
Who should not take Zestoretic?
Avoid if you are pregnant, have a history of angioedema with ACE inhibitors, are unable to make urine (anuria), or are taking aliskiren with diabetes. Use caution with significant kidney artery narrowing, severe kidney disease, liver disease, or known sulfonamide hypersensitivity to thiazides. Your clinician will determine suitability.
What lab tests or monitoring are needed on Zestoretic?
Expect periodic checks of blood pressure, kidney function (creatinine, eGFR), and electrolytes (especially potassium and sodium). Your clinician may also monitor uric acid, glucose, and lipids if you have risk factors. Testing is common within 1–2 weeks of starting or dose changes, then at regular intervals.
Can Zestoretic cause a cough?
Yes. The lisinopril component (an ACE inhibitor) can cause a persistent dry cough in some people. If the cough is bothersome or does not go away, talk to your clinician. An ARB-based alternative (such as losartan/hydrochlorothiazide) may be considered.
Does Zestoretic affect potassium or sodium levels?
It can. Lisinopril may increase potassium, while hydrochlorothiazide can lower potassium and sodium. The combination sometimes balances potassium, but either high or low potassium and low sodium are still possible. Your clinician will monitor labs and may advise on diet and supplements.
Does Zestoretic affect kidney function?
ACE inhibitors can cause a small, expected rise in creatinine when therapy begins, but large increases or a sudden drop in kidney function can occur, especially with dehydration, NSAID use, or renal artery stenosis. Hydrochlorothiazide is less effective when eGFR is below about 30 mL/min. Report decreased urine output, swelling, or unusual fatigue.
Can Zestoretic raise blood sugar or cholesterol?
Hydrochlorothiazide can modestly raise blood sugar, cholesterol, and triglycerides in some people, especially at higher doses. Most changes are small and manageable. The cardiovascular benefits of blood pressure control typically outweigh these effects, but your clinician may monitor and adjust your plan if needed.
Can Zestoretic worsen gout?
Yes. Hydrochlorothiazide can raise uric acid and may trigger gout flares. If you have gout or high uric acid, tell your clinician. Alternatives or preventive strategies (such as urate-lowering therapy) may be considered.
What should I do if I miss a dose of Zestoretic?
Take it as soon as you remember the same day. If it’s close to your next dose, skip the missed dose and resume your usual schedule. Do not double up. If you miss doses often, set reminders and talk to your clinician.
Which medications or supplements interact with Zestoretic?
Avoid or use caution with potassium supplements, potassium-sparing diuretics (spironolactone, eplerenone, amiloride), salt substitutes containing potassium, NSAIDs (ibuprofen, naproxen), lithium, and other blood pressure medicines that can intensify effects. Aliskiren with diabetes is not recommended. Always review your medication list with your clinician.
Is there a generic for Zestoretic?
Yes. Generic lisinopril/hydrochlorothiazide is widely available and typically costs less than the brand. Generics must meet the same FDA standards for quality and effectiveness.
Can I drink alcohol while taking Zestoretic?
Alcohol can enhance blood pressure–lowering effects and increase dizziness or fainting, especially when starting or increasing the dose, and it can worsen dehydration from the diuretic. If you drink, do so moderately, hydrate well, and rise slowly from sitting or lying positions.
Is Zestoretic safe during pregnancy?
No. ACE inhibitors like lisinopril can harm the developing fetus, especially in the second and third trimesters, and are generally avoided once pregnancy is planned or confirmed. If you become pregnant, stop Zestoretic and contact your clinician right away to switch to a safer alternative.
Can I take Zestoretic while breastfeeding?
Data on lisinopril during breastfeeding are limited; hydrochlorothiazide appears in breast milk and, at higher doses, may reduce milk supply. Many clinicians prefer alternative antihypertensives with more breastfeeding safety data. Discuss risks and options with your pediatrician and prescriber.
Should I stop Zestoretic before surgery or dental procedures?
ACE inhibitors may contribute to low blood pressure under anesthesia, and diuretics can increase dehydration risk. Your surgical team may advise holding Zestoretic the morning of major surgery (sometimes the day before) and restarting when you’re stable and drinking fluids. Follow your surgeon’s and anesthesiologist’s instructions.
What if I have vomiting, diarrhea, or heavy sweating on Zestoretic?
These can cause dehydration and electrolyte imbalances, raising the risk of low blood pressure or kidney injury. Temporarily hold Zestoretic if you cannot keep fluids down or are significantly dehydrated, and contact your clinician for guidance on when to resume.
Is Zestoretic safe if I have kidney disease?
ACE inhibitors can protect kidneys in some conditions, but hydrochlorothiazide is less effective in advanced kidney disease (eGFR <30 mL/min). Dose selection and close lab monitoring are essential. Your clinician may choose different diuretics or separate agents based on your kidney function.
Can I use salt substitutes or potassium supplements with Zestoretic?
Many salt substitutes contain potassium chloride, and lisinopril can raise potassium. Combining them increases the risk of dangerous hyperkalemia. Do not use potassium supplements or salt substitutes unless your clinician approves and monitors your levels.
How does Zestoretic compare to Prinzide?
They are the same medication: both combine lisinopril and hydrochlorothiazide in identical strengths. Effectiveness, side effects, and dosing are equivalent. Availability and price may differ by pharmacy and insurance.
Zestoretic vs lisinopril: which is better?
If lisinopril alone doesn’t control blood pressure or if you need multiple mechanisms, Zestoretic often lowers pressure more due to the added diuretic. If you’re sensitive to diuretics, at risk for gout, or have low sodium, lisinopril alone may be preferable. Your clinician can tailor therapy.
Zestoretic vs hydrochlorothiazide: which is better?
Zestoretic typically lowers blood pressure more than hydrochlorothiazide alone because it combines two complementary mechanisms. However, if you’ve had ACE inhibitor angioedema or are pregnant, hydrochlorothiazide alone may be safer. Individual risks and lab results guide the choice.
How does Zestoretic compare to Lotensin HCT (benazepril/HCTZ)?
Both pair an ACE inhibitor with hydrochlorothiazide and have similar blood pressure–lowering effects. Differences are mainly in the specific ACE inhibitor (lisinopril vs benazepril), dosing schedules, and how your body tolerates them. Choice often depends on response, side effects, and insurance coverage.
Zestoretic vs Accuretic (quinapril/HCTZ): what’s the difference?
Both are ACE inhibitor/thiazide combinations with similar efficacy. Some patients do better on one ACE inhibitor than another due to side effects like cough or dizziness. Monitoring and personal response guide selection.
Zestoretic vs Capozide (captopril/HCTZ): which is preferred?
Captopril has a shorter half-life and often requires dosing 2–3 times per day, while Zestoretic is once daily. For most people, once-daily options improve adherence. Captopril may be chosen in specific situations, but Zestoretic is typically more convenient.
How does Zestoretic compare to Hyzaar (losartan/HCTZ)?
Hyzaar uses an ARB instead of an ACE inhibitor. ARBs have a lower risk of cough and angioedema. Blood pressure reduction is comparable. If you developed an ACE inhibitor cough or angioedema, an ARB/HCTZ combination like Hyzaar is often preferred.
Zestoretic vs Diovan HCT (valsartan/HCTZ): which is better?
Both lower blood pressure effectively. Diovan HCT is an ARB/thiazide and may be better tolerated if you’ve had ACE inhibitor–related cough. Zestoretic may offer added kidney protection in certain conditions. Choice depends on tolerability, comorbidities, and cost.
Zestoretic vs Benicar HCT (olmesartan/HCTZ): how do they differ?
They are similar in overall efficacy. Olmesartan is an ARB, which avoids ACE inhibitor cough risk. Rarely, olmesartan has been linked to a sprue-like enteropathy. Selection depends on individual risk factors and response.
Zestoretic vs Micardis HCT (telmisartan/HCTZ): which should I choose?
Both are effective. Telmisartan has a long half-life and may provide smooth 24-hour control; it also has favorable metabolic data in some studies. Zestoretic may be chosen for ACE-specific benefits. Your clinician will consider side effect profile, kidney function, and insurance.
Zestoretic vs amlodipine: which lowers blood pressure better?
Both are first-line options. Amlodipine (a calcium channel blocker) works well across diverse populations and doesn’t affect electrolytes or uric acid. Zestoretic combines two mechanisms and may be superior when combination therapy is needed. Edema is more common with amlodipine; cough/angioedema are ACE-specific concerns.
Zestoretic vs amlodipine/benazepril (Lotrel): what’s the difference?
Zestoretic combines an ACE inhibitor with a thiazide; Lotrel combines an ACE inhibitor with a calcium channel blocker. Both are strong combinations. Lotrel avoids diuretic-related electrolyte shifts and gout risk, while Zestoretic may be better if you retain fluid or have salt-sensitive hypertension.
Zestoretic vs chlorthalidone combinations: which diuretic is better?
Chlorthalidone is a thiazide-like diuretic with a longer duration and, in some studies, stronger outcome data than hydrochlorothiazide, but it may cause more low potassium and sodium. Some clinicians prefer pairing an ACE inhibitor with chlorthalidone, though fixed lisinopril/chlorthalidone products are uncommon.
Is Zestoretic suitable as initial therapy compared with other combo pills?
For many patients with stage 2 hypertension or elevated cardiovascular risk, starting with a two-drug combination is recommended. Zestoretic is an appropriate initial option, comparable to ACE/CCB or ARB/HCTZ combinations. The best choice depends on side effect risks, kidney function, and individual response.