Lisinopril hctz 20 12

Zestoretic

SIDE EFFECTS

ZESTORETIC has been evaluated for safety in 930 patients including 100 patients treated for 50 weeks or more.

In clinical trials with ZESTORETIC no adverse experiences peculiar to this combination drug have been observed. Adverse experiences that have occurred have been limited to those that have been previously reported with lisinopril or hydrochlorothiazide.

The most frequent clinical adverse experiences in controlled trials (including open label extensions) with any combination of lisinopril and hydrochlorothiazide were: dizziness (7.5%), headache (5.2%), cough (3.9%), fatigue (3.7%) and orthostatic effects (3.2%) all of which were more common than in placebo-treated patients. Generally, adverse experiences were mild and transient in nature, but see WARNINGS regarding angioedema and excessive hypotension or syncope. Discontinuation of therapy due to adverse effects was required in 4.4% of patients principally because of dizziness, cough, fatigue and muscle cramps.

Adverse experiences occurring in greater than one percent of patients treated with lisinopril plus hydrochlorothiazide in controlled clinical trials are shown below.

Percent of Patients in Controlled Studies

Clinical adverse experiences occurring in 0.3% to 1.0% of patients in controlled trials and rarer, serious, possibly drug-related events reported in marketing experience are listed below:

Body as a Whole: Chest pain, abdominal pain, syncope, chest discomfort, fever, trauma, virus infection. Cardiovascular: Palpitation, orthostatic hypotension. Digestive: Gastrointestinal cramps, dry mouth, constipation, heartburn. Musculoskeletal: Back pain, shoulder pain, knee pain, back strain, myalgia, foot pain. Nervous/Psychiatric: Decreased libido, vertigo, depression, somnolence. Respiratory: Common cold, nasal congestion, influenza, bronchitis, pharyngeal pain, dyspnea, pulmonary congestion, chronic sinusitis, allergic rhinitis, pharyngeal discomfort. Skin: Flushing, pruritus, skin inflammation, diaphoresis, cutaneous pseudolymphoma. Special Senses: Blurred vision, tinnitus, otalgia. Urogenital: Urinary tract infection.

Angioedema: Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported (See WARNINGS).

In rare cases, intestinal angioedema has been reported in post marketing experience.

Cough: See PRECAUTIONS -Cough.

Clinical Laboratory Test Findings

Serum Electrolytes

(See PRECAUTIONS).

Creatinine, Blood Urea Nitrogen

Minor reversible increases in blood urea nitrogen and serum creatinine were observed in patients with essential hypertension treated with ZESTORETIC. More marked increases have also been reported and were more likely to occur in patients with renal artery stenosis (See PRECAUTIONS).

Serum Uric Acid, Glucose, Magnesium, Cholesterol, Triglycerides And Calcium

(See PRECAUTIONS).

Hemoglobin And Hematocrit

Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.5 g% and 1.5 vol%, respectively) occurred frequently in hypertensive patients treated with ZESTORETIC but were rarely of clinical importance unless another cause of anemia coexisted. In clinical trials, 0.4% of patients discontinued therapy due to anemia.

Liver Function Tests

Rarely, elevations of liver enzymes and/or serum bilirubin have occurred. (See WARNINGS, Hepatic Failure).

Other adverse reactions that have been reported with the individual components are listed below:

Lisinopril

In clinical trials adverse reactions which occurred with lisinopril were also seen with ZESTORETIC. In addition, and since lisinopril has been marketed, the following adverse reactions have been reported with lisinopril and should be considered potential adverse reactions for ZESTORETIC: Body as a Whole: Anaphylactoid reactions (see WARNINGS, Anaphylactoid Reactions During Membrane Exposure), malaise, edema, facial edema, pain, pelvic pain, flank pain, chills; Cardiovascular: Cardiac arrest, myocardial infarction or cerebrovascular accident, possibly secondary to excessive hypotension in high risk patients (see WARNINGS, Hypotension), pulmonary embolism and infarction, worsening of heart failure, arrhythmias (including tachycardia, ventricular tachycardia, atrial tachycardia, atrial fibrillation, bradycardia, and premature ventricular contractions), angina pectoris, transient ischemic attacks, paroxysmal nocturnal dyspnea, decreased blood pressure, peripheral edema, vasculitis; Digestive: Pancreatitis, hepatitis (hepatocellular or cholestatic jaundice) (see WARNINGS, Hepatic Failure), gastritis, anorexia, flatulence, increased salivation; Endocrine: Diabetes mellitus, inappropriate antidiuretic hormone secretion; Hematologic: Rare cases of bone marrow depression, hemolytic anemia, leukopenia/neutropenia, and thrombocytopenia have been reported in which a causal relationship to lisinopril can not be excluded; Metabolic: Gout, weight loss, dehydration, fluid overload, weight gain; Musculoskeletal: Arthritis, arthralgia, neck pain, hip pain, joint pain, leg pain, arm pain, lumbago; Nervous System/Psychiatric: Ataxia, memory impairment, tremor, insomnia, stroke, nervousness, confusion, peripheral neuropathy (e.g., paresthesia, dysesthesia), spasm, hypersomnia, irritability; mood alterations (including depressive symptoms); hallucinations; Respiratory: Malignant lung neoplasms, hemoptysis, pulmonary edema, pulmonary infiltrates, bronchospasm, asthma, pleural effusion, pneumonia, eosinophilic pneumonitis, wheezing, orthopnea, painful respiration, epistaxis, laryngitis, sinusitis, pharyngitis, rhinitis, rhinorrhea, chest sound abnormalities; Skin: Urticaria, alopecia, herpes zoster, photosensitivity, skin lesions, skin infections, pemphigus, erythema, psoriasis, rare cases of other severe skin reactions, including toxic epidermal necrolysis and Stevens-Johnson Syndrome (causal relationship has not been established); Special Senses: Visual loss, diplopia, photophobia, taste alteration, olfactory disturbance; Urogenital: Acute renal failure, oliguria, anuria, uremia, progressive azotemia, renal dysfunction (see PRECAUTIONS and DOSAGE AND ADMINISTRATION), pyelonephritis, dysuria, breast pain.

Miscellaneous

A symptom complex has been reported which may include a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia, fever, vasculitis, eosinophilia and leukocytosis. Rash, photosensitivity or other dermatological manifestations may occur alone or in combination with these symptoms.

Hydrochlorothiazide

Body as a Whole: Weakness; Digestive: Anorexia, gastric irritation, cramping, jaundice (intrahepatic cholestatic jaundice) (See WARNINGS, Hepatic Failure), pancreatitis, sialoadenitis, constipation; Hematologic: Leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia; Musculoskeletal: Muscle spasm; Nervous System/Psychiatric: Restlessness; Renal: Renal failure, renal dysfunction, interstitial nephritis (see WARNINGS); Skin: Erythema multiforme including Stevens-Johnson Syndrome, exfoliative dermatitis including toxic epidermal necrolysis, alopecia; Special Senses: Xanthopsia; Hypersensitivity: Purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions.

Read the entire FDA prescribing information for Zestoretic (Lisinopril and Hydrochlorothiazide)

25-30% of people with lupus experience hypertension (high blood pressure), which is defined as a blood pressure of greater than 140/90 mmHg. In addition, many more lupus patients have blood pressures greater than the normal 120/80 mmHg limit. The most common causes of high blood pressure in people with lupus are kidney disease and long-term steroid use. Other medications, such as cyclosporine (Neoral, Sandimmune, Gengraf) can also cause elevations in blood pressure.

High blood pressure can cause everyday headaches, but more importantly, it can lead to stroke, heart failure, and heart attack. Cardiovascular disease is the number one cause of death in people with lupus, so it is very important that your blood pressure is brought to the healthy 120/80 mmHg level and maintained. It is imperative that you take steps yourself to help achieve and maintain optimum cardiovascular health—remember, you play the most important role in your own well-being.

You can take several steps on your own to ensure that you remain as healthy as possible. Do not smoke, because smoking increases the risk of cardiovascular disease. In addition, it is important that you maintain a healthy diet and regular exercise regimen; these elements are especially significant for people taking steroid medications such as prednisone. A low-fat, low-cholesterol diet is essential for a healthy lifestyle. Focus on eating whole grains, vegetables, and lean sources of protein. Limit your sodium (i.e., salt) intake, since sodium levels are directly linked to blood pressure. In addition, try to exercise at least 30-minutes per day. This goal can be difficult for people with lupus who experience reoccurring joint and muscle pain, fatigue, and other symptoms, but engaging in low-impact daily activities such as walking, biking, yoga, Tai chi, and other forms of stretching may help to alleviate some of this pain while also helping you to maintain a healthy weight and a strong cardiovascular system. These activities also reduce the risk of osteoporosis, and people who exercise daily report that they actually feel better physically and mentally.

However, it is important to remember that while diet and exercise are extremely important for optimal cardiovascular health, these elements alone may be insufficient in controlling your blood pressure. Therefore, your doctor may prescribe a medication to help control your blood pressure. There are several types of medications that work to lower, control, and/or maintain blood pressure, and each works in a different way. Your doctor will work with you to evaluate and prescribe the blood pressure medication that best suits your personal condition. It is important that you remember to take your blood pressure (and other) medications as directed by your physician and notify him/her of any changes to your personal health. Take your blood pressure medications every day, including the days that you see your doctor. Do not stop taking your blood pressure medications without speaking to your doctor, since suddenly stopping your medication could put you in danger of a heart attack, stroke, or, in some cases, kidney failure.

Diuretics

Chlorthalidone (Hygroton)
Chlorothiazide (Diuril)
Hydrochlorothiazide (Esidrix, Hydrodiuril)
Indapamide (Lozol)
Metolazone (Zaroxolyn, Mykrox)
Bumetanide (Bumex)
Furosemide (Lasix)
Torsemide (Demadex)
Amiloride (Midamor)
Spironolactone (Aldactone)
Triamterene and hydrochlorothiazide (Dyazide)

Your kidneys play a very important role in helping to maintain blood pressure. A complex system of tubules in the kidney is responsible for regulating the balance of water and salts in your blood. When excess fluid and sodium build up in your kidneys, your blood pressure goes up. Diuretics (a.k.a., “water tablets,” or “water pills”) help to rid the kidneys of excess fluids and sodium through urination; in doing this, diuretics also help to reduce blood pressure. Diuretics are usually prescribed as the first line of treatment for high blood pressure but may also be given to enhance the effect of other medications.

There are actually four kinds of diuretics— thiazide diuretics, loop diuretics, potassium-sparing diuretics, and combination diuretics. Each class works on a different part of the nephron, the functional unit of the kidney that makes up its vast system of tubules. Thiazide diuretics (chlorthalidone, hydrochlorothiazide, indapamide, and metolazone) are sometimes the first drugs suggested for people with high blood pressure. These medications prevent the reabsorption of sodium and water in a specific part of the nephron called the distal convoluted tubule. In doing so, they also force more water into the urine to be removed from the body. Thiazides relax the muscles in blood vessel walls, allowing blood to flow more easily. Generally, thiazide diuretics are taken once daily. These medications can lower the amount of potassium in your body, so this factor will be monitored by your doctor.

Loop diuretics (bumetanide, furosemide, and torsemide) work on a part of the nephron called the “Loop of Henle” and prevent sodium from re-entering the blood. However, loop diuretics also interfere with the reabsorption of other salts, such as calcium, magnesium, and potassium. Proper monitoring may be necessary to prevent complications, such as low potassium. Your physican may recommend that you take a potassium supplement while taking these medications. Loop diuretics are generally less effective than thiazides for controlling blood pressure because they work for a shorter period of time and may result in a loss of blood pressure control at certain times in the day. These medications are generally taken once or twice daily.

Potassium-sparing diuretics (amiloride, spironolactone, and triamterene) are weaker than thiazides and loop diuretics but do not yield the potassium-depleting effects that loop diuretics do. These medications are sometimes used in combination with other diuretics, namely hydrochlorothazide (“HCTZ”). One example of a combination therapy is Dyazide (HCTZ/triamterene). Potassium-sparing diuretics are typically taken once daily.

Certain medications can interact with diuretics, so be sure to tell your doctor about any medications (both prescription and over-the-counter), vitamins, and supplements that you may be taking. Be especially wary of interactions with the following drugs: digitalis and digoxin (especially if your potassium level is low), certain antidepressants (especially when taking thiazide or loop-acting diuretics, other medications for high blood pressure, lithium, and cyclosporine (especially when taking a potassium-sparing diuretic).

Diuretics can cause certain side effects. Common side effects include weakness, muscle cramps, skin rash, increased sensitivity to sunlight (with thiazide diuretics), vomiting, diarrhea, cramps, lightheadedness, or joint pain. Less common side effects include impotence and irregular heartbeat. Many of these side effects can mimic lupus symptoms, so speak with your doctor if you feel that you are experiencing any new symptoms that may be caused by a new medication. However, it is important that you do not stop taking your medication unless both you and your doctor decide that this is the correct course of action. In addition to keeping your blood pressure under control, many anti-hypertensive medications also affect the function of your kidneys, so stopping your medication without appropriate approval could have serious consequences.

Angiotensin-Converting Enzyme (ACE) Inhibitors

Angiotensin-converting enzyme (ACE) inhibitors are used to control blood pressure, treat heart failure, lower protein in the urine, and prevent kidney damage. These medications make your heart’s work much more efficient by expanding blood vessels and decreasing resistance to blood flow. ACE is a chemical in your body that converts a hormone called angiotensin-I to angiotensin-II. Angiotensin-II is involved in several actions, one of which causes the muscles surrounding the blood vessels to contract. The narrowing of your blood vessels caused by this contraction causes your blood pressure to rise. As their name suggests, ACE inhibitors work to inhibit ACE, and in doing so, they also inhibit the production of Angiotensin-II. Because of this inhibition, the blood vessels dilate (enlarge), thereby reducing blood pressure and making it easier for your heart to pump blood. ACE inhibitors have a two-fold benefit for many lupus patients, because in addition to controlling blood pressure, they also decrease protein in the urine (proteinuria), and thus help to prevent kidney scarring in lupus patients with kidney involvement. ACE inhibitors should be used carefully, however, in people with renal artery stenosis (narrowing of the artery that supplies blood to the kidney).

Most people tolerate ACE inhibitors well, but these medications do have some potential side effects. The most common side effects are a cough which may last up to a month, elevated blood potassium levels, low blood pressure, constipation, dizziness, headache, drowsiness, weakness, metallic or salty taste, and rash. Rare, but serious, side effects include kidney failure, allergic reactions, a decrease in white blood cell count, and a swelling of the tissue just below the skin (angioedema). In addition, women who are pregnant or may become pregnant should not take ACE inhibitors because they are known to cause birth defects.

Be sure to tell your doctor about any other medications, vitamins, or supplements you may be taking, since certain medications can interact with ACE inhibitors. Be especially cautious with potassium supplements, salt substitutes (which can contain potassium), and other drugs that can affect the amount of potassium in your blood, since ACE inhibitors may increase your potassium levels. ACE inhibitors may also increase the concentration of lithium (Eskalith) in the blood of people taking this medication, which can cause an increase in side effects.

Angiotensin-II Receptor Antagonists / Angiotensin Receptor Blockers (ARBs)

Candesartan (Atacand)
Eprosartan (Teveten)
Irbesartan (Avapro)
Losartan (Cozaar)
Telmisartan (Micardis)
Valsartan (Diovan)

Angiotensin-II receptor blockers (ARBs) are used to control high blood pressure, treat heart failure, lower protein in the urine, and prevent kidney failure. They are similar to ACE inhibitors, but their mechanism of action is slightly different. In your body, there are many substances that send messages to different cells and tissues to enact certain changes. However, in order for the signals to go through, there are often molecules that receive these substances to help transmit messages. Whereas ACE inhibitors block the formation of angiotensin-II, angiotensin-II receptor blockers block the molecules in your body that receive angiotensin-II so that the substance cannot transmit the signal for your blood vessels to contract. Therefore, your blood vessels remain enlarged, which keeps your blood pressure from rising and makes it easier for your heart to pump blood. Like ACE inhibitors, angiotensin receptor blockers also reduce proteinuria (excess protein in the urine) in people with lupus nephritis, which helps to keep the kidneys safe and healthy. The benefit of angiotensin-II receptor blockers is that they produce less cough as a side effect; if you experienced a cough from ACE inhibitors, you will most likely be switched to an ARB.

Like ACE inhibitors, ARBs are tolerated well by most people, but they do have some side effects. The most common side effects are elevated blood potassium levels, low blood pressure, dizziness, headache, drowsiness, weakness, metallic or salty taste, and rash. Cough can occur, but this happens less often with ARBs than with ACE inhibitors. The most serious (but rare) side effects include kidney failure, liver failure, allergic reactions, a decrease in white blood cells, and swelling of the tissue just bellow the skin (angioedema). In addition, women who are pregnant or may become pregnant should not take ARBs because they are known to cause birth defects.

Be sure to tell your doctor about any other medications, vitamins, or supplements you may be taking, since certain medications can interact with ARBs. Be especially cautious with potassium supplements, salt subsitutes (which can contain potassium), and other drugs that can affect the amount of potassium in your blood, since ARBs may increase your potassium levels. ARBs may also increase the concentration of lithium (Eskalith) in the blood of people taking this medication, which can cause an increase in side effects.

Beta Blockers

Beta blockers are used to lower blood pressure, treat abnormal heart rhythms and angina (chest pain and discomfort that occurs when your heart muscle does not get enough blood), and improve survival in people who have had a heart attack. Beta blockers are so-named because they block the action of adrenaline (a.k.a., epinephrine) and other substances in the body on “beta” receptors, which in turn slows the nerve impulses that travel to the heart. In doing this, beta blockers relieve stress on your heart, slow your heart beat, and lessen the force with which your heart muscle contracts. These medications also reduce the strength with which the muscles surrounding the blood vessels contract throughout the body, reducing pressure in your blood vessels and increasing blood flow. By allowing your blood to flow more easily and relieving some of the stress on your heart, beta blockers decrease heart rate, cardiac output, and ultimately blood pressure.

Beta blockers may cause certain side effects. Common side effects include drowsiness or fatigue, weakness or dizziness, and dry mouth, eyes, and skin. These medications may also cause cold hands and feet, which can be especially problematic for lupus patients experiencing Raynaud’s phenomenon. Less common side effects include wheezing or shortness of breath, slow heartbeat, trouble sleeping/vivid dreams, and swelling of the hands and feet. Rare side effects include abdominal cramps, vomiting, diarrhea, constipation, back or joint pain, skin rash, sore throat, depression, memory loss/confusion, and impotence. Tell your doctor right away if you experience any of these side effects.

While taking beta blockers, it is important that you do not drink alcohol, since alcohol can decrease the effects of these medications. In addition, avoid caffeine and over-the-counter cough and cold medicines, antihistamines, and antacids that contain aluminum. Be sure to tell your doctor about any medications, vitamins, and supplements that you may be taking, especially other blood pressure medications, anti-depressants, allergy shots, and diabetes and/or asthma medications. If you are pregnant or may become pregnant you should discuss your beta blocker medications with your doctor, since this drug should only be used during pregnancy if it is clearly needed.

Calcium Channel Blockers

Calcium channel blockers, also known as “calcium antagonists,” are used to decrease blood pressure and treat angina (chest pain) and some arrhythmias (abnormal heart rhythms). They are also used to treat Raynaud’s phenomenon, a cold-induced blue/purple color change in the fingers and toes. Calcium channel blockers work by interrupting the movement of calcium into the heart and blood vessel cells, which in turn decreases the force of contraction of the myocardium (muscle of the heart) and relaxes and widens blood vessels. Many calcium channel blockers also slow down the conduction of electricity in the heart, which lowers heart rate and thus further lowers blood pressure.

Calcium channel blockers may have some side effects, the most common of which are constipation, nausea, headache, rash, edema (swelling of the legs with fluid), low blood pressure, drowsiness, and dizziness.

If you are experiencing heart failure, you should not take diltiazem (Cardizem, Tiazac) or verapamil (Calan, Isoptin, Verelan), since these drugs reduce the ability of your heart to pump blood. In addition, you should tell your doctor about any other medications, vitamins, or supplements that you may be taking, especially other heart or blood pressure medications, anti-seizure medication, and cyclosporine (Neoral, Sandimmune, Gengraf). Diltiazem and verapamil interact most with other medications because these two calcium channel blockers decrease the elimination of certain drugs from the liver, including carbamazepine (Tegretol), simvastatin (Zocor), atorvastatin (Lipitor), and lovastatin (Mevacor). Since your liver cannot eliminate these substances as efficiently, they may accumulate in your blood, an effect which can be toxic to your body.

While taking calcium channel blockers, do not eat grapefruit or drink grapefruit juice, since grapefruit may increase some of the effects of these medications. Also avoid alcohol, since it interferes with the effects of these medications and may increase their side effects. If you are pregnant, talk to your doctor about whether you should continue therapy with calcium channel blockers. No pregnancy problems or birth complications have been found to date in humans, but you should always speak with your doctor about the risks and benefits of any medications you may be taking while pregnant.

Alpha Blockers

Doxazosin mesylate (Cardura)
Prazosin hydrochloride (Minipress)
Prazosin and polythiazide (Minizide)
Terazosin hydrochloride (Hytrin)
Tamsulosin (Flomax)

Alpha blockers are sometimes used to treat high blood pressure, Raynaud’s disease, scleroderma, and other conditions. They are also helpful in men who have difficulty urinating due to benign prostatic hyperplasia (BPH). Alpha blockers are generally not the first treatment option chosen to treat high blood pressure because they have not proven to reduce long-term risk of heart attack and stroke, but they are commonly used, often in combination with other drugs, when blood pressure is difficult to control.

Like beta blockers, alpha blockers block the action of receptor molecules (called alpha receptors) from receiving certain chemical messages. Specifically, alpha blockers attach themselves to alpha receptors found on blood vessels, in the prostate, and in special blood pressure sensors called baroreceptors. In doing this, alpha blockers prevent alpha receptors from receiving signals from the hormone norepinephrine (noradrenaline) to stimulate the muscles in the walls of smaller arteries and veins and cause them to constrict. By preventing this communication, alpha blockers cause the vessels to remain open and relaxed, improving blood flow and lowering blood pressure.

Alpha blockers fall into two categories—short-acting and long-acting. Short-acting alpha blockers work quickly, but their effects do not last as long. Long-acting medications take longer to begin working, but their effects last for longer periods of time. Your doctor will advise you on the type of alpha blocker that is best for you.

When you start taking alpha blockers, you may have what is known as a “first dose” effect. This effect may cause you to experience pronounced low blood pressure and dizziness which may make you faint when rising too quickly from the sitting or lying position, a phenomenon known as orthostatic hypotension or postural hypotension. To prevent this from happening, be sure to rise slowly whenever you begin to stand up. Your doctor may try to reduce the first dose phenomenon by starting you at a low dose and gradually increasing it until you reach the proper amount. In addition, most doctors recommend that you take alpha blockers before bed, which may help to lessen this effect. Other potential side effects can include headache, pounding heartbeat, nausea, weakness, weight gain, and small increases in LDL levels (“bad cholesterol”).

If you are pregnant or may become pregnant, speak with your doctor about whether continuing treatment with alpha blockers is right for you. Also tell your doctor about any medications (both prescription and over-the-counter), vitamins, and supplements that you may be taking, especially other blood pressure medications, NSAIDs, immunosuppressives, impotence therapy agents, antibiotics, anti-fungals, HIV medications, anti-depression and anti-anxiety drugs, diabetic medications, and certain asthma medicines. Stay away from diet pills, caffeine, and over-the-counter cough, medicines, cold medicine, and anti-histamines while taking alpha blockers, since these medications may increase blood pressure. Also avoid grapefruit and grapefruit juice because grapefruit interferes with the liver’s ability to get rid of certain substances, allowing them to accumulate to toxic levels. Alcohol can have a similar effect, so people taking alpha blockers—and all people with high blood pressure—should limit alcohol use.

Central Alpha Agonists / Central-Acting Agents

Clonidine hydrochloride (Catapres)
Clonidine hydrochloride and chlorthalidone (Clorpres, Combipres)
Guanabenz acetate (Wytensin)
Guanfacine hydrochloride (Tenex)
Methyldopa (Aldomet)
Methyldopa and chlorothiazide (Aldochlor)
Methyldopa and hydrochlorothiazide (Aldoril)

Central-acting agents work to lower your heart rate and blood pressure by preventing your brain from sending signals to the nervous system to speed up heart rate and narrow blood vessels. As a result, your heart does not have to work as hard and the blood flows more easily through your blood vessels. Central-acting agents are not commonly used because they can cause strong side effects, including extreme fatigue, drowsiness/sedation, dizziness, impotence, constipation, dry mouth, headache, weight gain, impaired thinking and psychological problems like depression. Tell your doctor if experience these side effects, but do not stop taking your medication unless directed to do so by your doctor. If you are to stop taking central-acting agents, your doctor will advise you on how to gradually taper your dosage. Treatment with central-acting agents should not be stopped abruptly, since this can cause a sudden, dangerous increase in blood pressure. Also, be sure to speak to your doctor about any other medications you may be taking, since certain drugs may interfere with these medications.

Combination Therapies

Several combination therapies are available to help control, lower, and/or maintain your blood pressure. Common combination therapies are listed below. Your doctor can advise you of any special considerations regarding these medications.

General

Atenolol and chlorthalidone (Tenoretic)
Bisoprolol and hydrochlorothiazide (Ziac)
Nadolol and bendroflumethiazide (Corzide)
Propranolol and hydrochlorothiazide (Inderide)
Timolol and hydrochlorothiazide (Timolide)

ACE Inhibitor/Diuretic

Benazepril and hydrochlorothiazide (Lotensin)
Enalapril and hydrochlorothiazide (Vaseretic)
Lisinopril and hydrochlorothiazide (Prinzide, Zestoretic)
Moexipril and hydrochlorothiazide (Uniretic)
Quinapril and hydrochlorothiazide (Accuretic)

Angtiotensin II Receptor Antagonist/Diuretic

Irbesartan and hydrochlorothiazide (Avalide)
Losartan and hydrochlorothiazide (Hyzaar)
Valsartan and hydrochlorothiazide (Diovan HCT)

ACE Inhibitor/Calcium Channel Blocker

Amlodipine and benazepril (Lotrel)
Enalapril and felodipine (Lexxel)
Trandolapril and verapamil (Tarka)

Combined Alpha and Beta Blocker Action

Labetalol hydrochloride (Normodyne)

Zestoretic 10

ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.

Renal function impairment

Thiazides may not be appropriate diuretics for use in patients with renal impairment and are ineffective at creatinine clearance values of 30 ml/min or below (corresponds to moderate or severe renal insufficiency).

Lisinopril/hydrochlorothiazide should not be administered to patients with renal insufficiency (creatinine clearance less than or equal to 80 ml/min) until titration of the individual components has shown the need for the doses present in the combination tablet.

In patients with heart failure, hypotension following the initiation of therapy with ACE inhibitors may lead to some further impairment in renal function. Acute renal failure, usually reversible, has been reported in this situation.

In some patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, who have been treated with ACE inhibitors, increases in blood urea and serum creatinine, usually reversible upon discontinuation of therapy, have been seen. This is especially likely in patients with renal insufficiency. If renovascular hypertension is also present there is an increased risk of severe hypotension and renal insufficiency. In these patients, treatment should be started under close medical supervision with low doses and careful dose titration. Since treatment with diuretics may be a contributory factor to the above, renal function should be monitored during the first few weeks of lisinopril/hydrochlorothiazide therapy.

Some hypertensive patients with no apparent pre-existing renal disease have developed usually minor and transient increases in blood urea and serum creatinine when lisinopril has been given concomitantly with a diuretic.

This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of the diuretic and/or lisinopril may be required.

Prior diuretic therapy

The diuretic therapy should be discontinued for 2-3 days prior to initiation with lisinopril/hydrochlorothiazide. If this is not possible, treatment should be started with lisinopril alone, in a 5 mg dose.

Renal transplantation

Should not be used, since there is no experience with patients recently transplanted with a kidney.

Anaphylactoid reactions in haemodialytic patients

The use of lisinopril/hydrochlorothiazide is not indicated in patients requiring dialysis for renal failure. Anaphylactoid reactions have been reported in patients, undergoing certain haemodialysis procedures (e.g. with the high-flux membranes AN 69 and during low-density lipoproteins (LDL) apheresis with dextran sulphate) and treated concomitantly with an ACE inhibitor. In these patients consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent.

Anaphylactoid reactions related to low-density lipoproteins (LDL) apheresis

In rare occasions, patients treated with ACE inhibitors during low-density lipoprotein (LDL) apheresis with dextran sulfate have shown life threatening anaphylactic reactions. These symptoms could be avoided by temporary discontinuation of the treatment with ACE inhibitors before each apheresis.

Hepatic impairment

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 (see section 4.3). Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice or hepatitis and progresses to fulminant necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving lisinopril/hydrochlorothiazide who develop jaundice or marked elevations of hepatic enzymes should discontinue lisinopril/hydrochlorothiazide and receive appropriate medical follow-up.

Surgery/anaesthesia

In patients undergoing major surgery or during anaesthesia with agents that produce hypotension, lisinopril may block angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.

Metabolic and endocrine effects

ACE inhibitor and thiazide therapy may impair glucose tolerance. Dosage adjustment of antidiabetic agents, including insulin, may be required. In diabetic patients treated with oral antidiabetic agents or insulin, glycaemia levels should be closely monitored during the first month of treatment with an ACE inhibitor. Latent diabetes mellitus may become manifest during thiazide therapy.

Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy.

Thiazide therapy may precipitate hyperuricaemia and/or gout in certain patients. However, lisinopril may increase urinary uric acid and thus may attenuate the hyperuricaemic effect of hydrochlorothiazide.

Electrolyte imbalance

As for any patient receiving diuretic therapy, periodic determination of serum electrolytes should be performed at appropriate intervals.

Thiazides, including hydrochlorothiazide, can cause fluid or electrolyte imbalance (hypokalaemia, hyponatraemia, and hypochloremic alkalosis). Warning signs of fluid or electrolyte imbalance are dryness of mouth, thirst, weakness, lethargy, drowsiness, muscle pain or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea or vomiting. Dilutional hyponatraemia may occur in oedematous patients in hot weather. Chloride deficit is generally mild and does not require treatment. Thiazides have been shown to increase the urinary excretions of magnesium, which may result in hypomagnesaemia.

Thiazides may decrease urinary calcium excretion and may cause intermittent and slight elevation of serum calcium. Marked hypercalcaemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function.

Hyperkalaemia

Elevations in serum potassium have been observed in some patients treated with ACE inhibitors, including lisinopril. Patients at risk for the development of hyperkalaemia include those with renal insufficiency, diabetes mellitus, or those using concomitant potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes, or those patients taking other drugs associated with increases in serum potassium (e.g. heparin, the combination trimethoprim/sulfamethoxazole also known as co-trimoxazole). If concomitant use of the above-mentioned agents is deemed appropriate, regular monitoring of serum potassium is recommended (see section 4.5).

Diabetic patients

In diabetic patients treated with oral antidiabetic agents or insulin, glycaemic control should be closely monitored during the first month of treatment with an ACE inhibitor (see section 4.5).

Hypersensitivity/angioedema

Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported uncommonly in patients treated with ACE inhibitors, including lisinopril. This may occur at any time during therapy. In such cases, lisinopril should be discontinued promptly and appropriate treatment and monitoring should be instituted to ensure complete resolution of symptoms prior to dismissing the patient. Even in those instances where swelling of only the tongue is involved, without respiratory distress, patients may require prolonged observation since treatment with anti-histamines and corticosteroids may not be sufficient.

Very rarely, fatalities have been reported due to angioedema associated with laryngeal oedema or tongue oedema. Patients with involvement of the tongue, glottis or larynx, are likely to experience airway obstruction, especially those with a history of airway surgery. In such cases emergency therapy should be administered promptly. This may include the administration of adrenaline and/or the maintenance of a patent airway. The patient should be under close medical supervision until complete and sustained resolution of symptoms has occurred.

ACE inhibitors cause a higher rate of angioedema in black patients than in non-black patients.

Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see section 4.3).

Patients taking concomitant mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) therapy may be at increased risk of angioedema (e.g. swelling of the airways or tongue, with or without respiratory impairment) (see section 4.5).

In patients receiving thiazides, hypersensitivity reactions may occur with or without a history of allergy or bronchial asthma. Exacerbation or activation of systemic lupus erythematosus has been reported with the use of thiazides.

Desensitisation

Patients receiving ACE inhibitors during desensitisation treatment (e.g. hymenoptera venom) have sustained anaphylactoid reactions. In the same patients, these reactions have been avoided when ACE inhibitors were temporarily withheld but they reappeared upon inadvertent rechallenge.

Neutropenia/agranulocytosis

Neutropenia/agranulocytosis, thrombocytopenia and anaemia have been reported for patients receiving ACE inhibitors. In patients with normal renal function and no other complicating factors neutropenia occurs rarely. Neutropenia and agranulocytosis are reversible after discontinuation of the ACE inhibitor. Lisinopril should be used with extreme caution in patients with collagen vascular disease, immunosuppressant therapy, treatment with allopurinol or procainamide, or a combination of these complicating factors, especially if there is pre-existing impaired renal function. Some of these patients developed serious infections, which in a few instances did not respond to intensive antibiotic therapy. If lisinopril is used in such patients, periodic monitoring of white blood cell counts is advised and patients should be instructed to report any sign of infection.

Race

ACE inhibitors cause a higher rate of angioedema in black patients than in non-black patients.

As with other ACE inhibitors, lisinopril may be less effective in lowering blood pressure in black patients than in non-black patients, possibly because of a higher prevalence of low-renin states in the black hypertensive population.

Cough

Cough has been reported with the use of ACE inhibitors. Characteristically, the cough is non-productive, persistent and resolves after discontinuation of therapy. ACE inhibitor-induced cough should be considered as part of the differential diagnosis of cough.

Lithium

The combination of ACE inhibitors and lithium is generally not recommended (see section 4.5).

Anti-doping test

The hydrochlorothiazide contained in this medication could produce a positive analytic result in an anti-doping test.

Pregnancy

ACE inhibitors should not be initiated during pregnancy. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).

lisinopril/hydrochlorothiazide (Rx)

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

Contraindications

Hypersensitivity to ACE inhibitors, thiazides, or sulfonamides

ACE-inhibitor induced angioedema, hereditary or idiopathic angioedema

Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan

Anuria or renal stenosis

Do not coadminister with aliskiren in patients with diabetes mellitus or with renal impairment (ie, GFR

Cautions

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 is symptoms occur

Dry hacking nonproductive cough may occur within few months of treatment; consider other causes of cough prior to discontinuation

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 renal impairment are at high risk; monitor CBC with differential in these patients

Photosensitization may occur

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

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

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

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