Zestoretic 20/12.5mg Tablets

Lisinopril is an ACE inhibitor that prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. This leads to decreased angiotensin II levels, resulting in vasodilation, reduced aldosterone secretion (leading to decreased sodium and water reabsorption and increased potassium retention), and decreased sympathetic activity. Hydrochlorothiazide is a thiazide diuretic that inhibits sodium and chloride reabsorption in the distal convoluted tubule, leading to increased excretion of sodium, chloride, and water, and to a lesser extent, potassium and magnesium. It also decreases calcium excretion. The combination provides additive antihypertensive effects and helps mitigate some of the electrolyte imbalances (e.g., hypokalemia from HCTZ, hyperkalemia from lisinopril).

Urgent Side Effects: Seek Medical Help Right Away

Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:

Allergic Reaction: Rash, hives, itching, red, swollen, blistered, or peeling skin with or without fever, wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
High Blood Sugar: Confusion, feeling sleepy, unusual thirst or hunger, frequent urination, flushing, fast breathing, or fruity-smelling breath.
Kidney Problems: Inability to urinate, changes in urine output, blood in the urine, or significant weight gain.
Fluid and Electrolyte Imbalance: Mood changes, confusion, muscle pain or weakness, irregular heartbeat, severe dizziness or fainting, increased thirst, seizures, fatigue, weakness, decreased appetite, changes in urine output, dry mouth, dry eyes, or severe nausea and vomiting.
Chest Pain or Persistent Cough: Seek medical attention if you experience chest pain or a cough that does not subside.
Severe Stomach Pain: Contact your doctor if you experience severe stomach pain.
Eye Problems: This medication can cause eye problems that may lead to permanent vision loss if left untreated. If you notice changes in vision or eye pain, typically within hours to weeks of starting the medication, contact your doctor immediately.
Liver Problems: In rare cases, this medication can cause liver damage, which can be fatal. Seek medical help if you experience dark urine, fatigue, decreased appetite, nausea, stomach pain, light-colored stools, vomiting, or yellowing of the skin and eyes.
Skin Cancer: Rarely, people taking hydrochlorothiazide have developed certain types of skin cancer. Protect your skin from the sun and follow your doctor's recommendations for skin checks. Contact your doctor if you notice any changes in the size or color of a mole, or any new or changing skin growths.
Low White Blood Cell Count: This medication can cause a decrease in white blood cell count, increasing the risk of infection. If you have kidney problems or other underlying health conditions, you may be more susceptible. Seek medical attention if you experience fever, chills, or sore throat.

Other Possible Side Effects

Most people do not experience significant side effects, but some may occur. If you notice any of the following symptoms or any other side effects that bother you or do not subside, contact your doctor:

Dizziness, fatigue, or weakness
Headache
* Cough

This is not an exhaustive list of potential side effects. If you have questions or concerns, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.

Before Taking This Medication: Important Information to Share with Your Doctor

It is essential to inform your doctor about the following conditions to ensure safe treatment:

Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction you experienced, including any symptoms.
A known sulfa allergy.
A history of angioedema, a severe and potentially life-threatening reaction characterized by swelling of the hands, face, lips, eyes, tongue, or throat, difficulty breathing, swallowing problems, or unusual hoarseness.
Kidney disease or any kidney problems.
Inability to urinate.
Current or recent use of specific medications, including:
+ Dofetilide.
+ Lithium.
+ Aliskiren-containing medications, especially if you have diabetes or kidney problems.
+ Sacubitril-containing medications within the last 36 hours.

This list is not exhaustive, and it is crucial to disclose all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, as well as any health issues, to your doctor and pharmacist. They will help you determine if it is safe to take this medication with your existing treatments and health conditions. Never start, stop, or adjust the dosage of any medication without consulting your doctor first.

Important Warnings and Cautions

It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.

To ensure your safety, avoid driving and other activities that require alertness until you understand how this medication affects you. When changing positions, rise slowly from a sitting or lying down position to minimize the risk of dizziness or fainting. Be cautious when navigating stairs.

Before consuming alcohol, marijuana, or other forms of cannabis, or taking prescription or over-the-counter (OTC) medications that may cause drowsiness, consult with your doctor.

If you have diabetes (high blood sugar), closely monitor your blood sugar levels. Regularly undergo blood work, blood pressure checks, and other laboratory tests as advised by your doctor. Be aware that this medication may interfere with certain lab tests, so inform all your healthcare providers and laboratory personnel that you are taking this medication.

If you are using a salt substitute containing potassium, a potassium-sparing diuretic, or a potassium product, discuss this with your doctor. Additionally, if you are on a low-salt or salt-free diet, consult with your doctor before continuing.

Before using OTC products that may increase blood pressure, such as cough or cold medications, diet pills, stimulants, non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or naproxen, or certain natural products or aids, consult with your doctor.

If you are taking cholestyramine or colestipol, consult with your pharmacist about the proper administration of these medications with this drug. Be aware of the potential for gout attacks.

If you have lupus, this medication may exacerbate or reactivate the condition. Immediately inform your doctor if you experience any new or worsening symptoms. In hot weather or during physical activity, be cautious and drink plenty of fluids to prevent dehydration. If you experience excessive sweating, fluid loss, vomiting, or diarrhea, inform your doctor, as these symptoms may lead to low blood pressure.

High cholesterol and triglyceride levels have been associated with this medication. If you have a history of high cholesterol or triglycerides, discuss this with your doctor.

A severe and potentially life-threatening reaction called angioedema has been reported, with a higher risk observed in Black patients.

If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.

If you are breastfeeding, consult with your doctor to discuss any potential risks to your baby.

• Aliskiren (in patients with diabetes or renal impairment (GFR < 60 mL/min/1.73 m²))
• Sacubitril/Valsartan (Entresto) - concomitant use or within 36 hours of switching due to increased risk of angioedema

• Potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride) - increased risk of hyperkalemia
• Potassium supplements or salt substitutes containing potassium - increased risk of hyperkalemia
• Lithium - increased serum lithium levels and toxicity (due to reduced renal clearance by both components)
• NSAIDs (e.g., ibuprofen, naproxen, celecoxib) - may reduce antihypertensive effect and increase risk of renal impairment (including acute renal failure), especially in elderly or volume-depleted patients
• Gold (sodium aurothiomalate) - nitritoid reactions (facial flushing, nausea, vomiting, hypotension) reported rarely with concomitant injectable gold and ACE inhibitors

• Other antihypertensive agents - additive hypotensive effects
• Corticosteroids - increased risk of hypokalemia
• Digoxin - increased risk of digoxin toxicity due to hypokalemia induced by HCTZ
• Antidiabetic agents (insulin, oral hypoglycemics) - HCTZ may decrease glucose tolerance, requiring dose adjustment of antidiabetics; lisinopril may enhance insulin sensitivity
• Cholestyramine and colestipol resins - may impair absorption of HCTZ
• Skeletal muscle relaxants, non-depolarizing (e.g., tubocurarine) - HCTZ may potentiate their effect
• Allopurinol - increased risk of hypersensitivity reactions with HCTZ
• Amantadine - increased risk of amantadine toxicity with HCTZ
• Cytotoxic agents (e.g., cyclophosphamide, methotrexate) - HCTZ may reduce renal excretion of these drugs, increasing myelosuppressive effects

• Alcohol, barbiturates, or narcotics - may potentiate orthostatic hypotension
• Pressor amines (e.g., norepinephrine) - HCTZ may decrease arterial responsiveness to pressor amines

• Dizziness or lightheadedness (especially upon standing)
• Swelling of face, lips, tongue, or throat (angioedema)
• Difficulty breathing or swallowing
• Persistent dry cough
• Muscle cramps or weakness (electrolyte imbalance)
• Unusual tiredness or weakness
• Nausea, vomiting, or diarrhea
• Signs of dehydration (dry mouth, thirst)
• Yellowing of skin or eyes (jaundice)
• Signs of infection (fever, sore throat) - rare, but possible blood dyscrasias

Contraindicated. Zestoretic can cause injury and death to the developing fetus when administered to pregnant women. If pregnancy is detected, discontinue Zestoretic as soon as possible.

Not recommended. Both lisinopril and hydrochlorothiazide are excreted in human milk. Lisinopril is excreted in very small amounts, but hydrochlorothiazide can suppress lactation and may cause adverse effects in the infant (e.g., electrolyte disturbances). The potential for serious adverse reactions in breastfed infants should be considered.

Safety and effectiveness in pediatric patients have not been established. Not recommended for use in children.

No overall differences in effectiveness or safety have been observed between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients may be more susceptible to the hypotensive effects and changes in renal function. Initiate therapy with lower doses and titrate carefully, monitoring renal function and electrolytes closely.

• Zestoretic is a fixed-dose combination and should not be used for initial therapy of hypertension. Patients should be titrated on individual components first, then switched to the combination if appropriate.
• Monitor for angioedema, especially in the first few weeks of therapy. Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk.
• A persistent dry cough is a common side effect of ACE inhibitors and usually resolves upon discontinuation. If bothersome, consider switching to an ARB/diuretic combination.
• Monitor serum potassium levels closely, as lisinopril tends to increase potassium and HCTZ tends to decrease it, potentially balancing each other out, but imbalances can still occur.
• Advise patients to report any signs of dehydration or excessive fluid loss (e.g., severe vomiting, diarrhea) as this can lead to acute renal failure or symptomatic hypotension.
• Thiazide diuretics can cause photosensitivity; advise patients to use sun protection.

• Other classes of antihypertensives (e.g., ARBs, Calcium Channel Blockers, Beta-blockers, other diuretics)
• Monotherapy with Lisinopril or Hydrochlorothiazide
• Lifestyle modifications (diet, exercise, weight management)

If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it occurred.