#aliskiren indication

[drpedi07]

Aliskiren Drug

Medical information for Aliskiren on Pediatric Oncall including Indication, Dosing, Adverse Effect, Renal Dose, Hepatic Dose.

[siglerprescriptiondrugcards]

Valsartan with Hydrochlorothiazide

Brand Name: Diovan-HCT

Generic Available

Common Dosage Forms:

80/12.5 Tablets: 80 mg valsartan with 12.5 mg hydrochlorothiazide (HCTZ)

160/12.5 Tablets: 160 mg valsartan with 12.5 mg HCTZ

160/25 Tablets: 160 mg valsartan with 25 mg HCTZ

320/12.5 Tablets: 320 mg valsartan with 12.5 mg HCTZ

320/25 Tablets: 320 mg valsartan with 25 mg HCTZ

FDA Indications/Dosages:

For the treatment of hypertension: This fixed dose combination may be used in patients who are likely to need multiple drugs to achieve their blood pressure goals. The combination may be substituted for the titrated components. The usual starting dose of valsartan is 80 mg once daily. The maximum dosage is 320 mg daily. The normal dosage is one tablet daily.

Monitor: CrCl, BP, K

Pharmacology/Pharmacokinetics: Angiotensin II is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Valsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues. Valsartan peak plasma concentration is reached in 2-4 hours after an oral dose. Elimination half-life is about 6 hours. Food decreases absorption and peak plasma concentration by about 50%. Elimination occurs primarily as unchanged drug in the feces (83%) and urine (13%). Hydrochlorothiazide inhibits the reabsorption of sodium and chloride at the distal renal tubule. It reaches peak plasma levels in 4 hours with a half-life of 6-15 hours. Excretion of unchanged drug occurs in the urine.

Drug Interactions: HCTZ may decrease sulfonylurea hypoglycemia. Electrolyte disturbances may cause DIGITALIS-induced arrhythmias. HCTZ use with diazoxide may cause hyperglycemia. HCTZ may increase lithium serum levels. NSAIDs, including COX-2 inhibitors, may decrease effects and increase risk of renal function deterioration. Increased adverse effects may occur when used with other renin-angiotensin system clockers or aliskiren.

Contraindications/Precautions: Contraindicated with aliskiren. DO NOT USE DURING PREGNANCY. Use with caution in nursing mothers. Valsartan has been shown to be excreted in the milk of lactating rats. HCTZ is contraindicated in patients with anuria or who are hypersensitive to sulfonamide-derived drugs. Use with caution in volume- or salt-depleted drugs due to excessive hypotension. Use with caution in patients with impaired hepatic or renal function. Pregnancy Category D.

Adverse Effects: Dizziness (9%), viral infection (3%), fatigue (5%), pharyngitis (3%), coughing (3%), and diarrhea (3%).

Patient Consultation:

May be administered with or without food.

When pregnancy is detected, discontinue use as soon as possible.

Store in a cool, dry place away from sunlight and children.

Dizziness may occur during the first few days of treatment, report to a physician if this adverse effect persists.

Contact a physician if the above side effects are severe or persistent.

[weonline-blog1]

MALEGRA 120 MG

Description:-

 malegra 120 is marketed globally by Sunrise Remedies and is available at every leading online pharmacy, madicinestore and medical supply store. The active ingredient present in Malegra 120 is Sildenafil Citrate. Sildenafil Citrate is used in the treatment of:

Erectile Dysfunction (inadequate penile erection during sexual activity)

Pulmonary Hypertension (high pressure in blood vessels of lungs)

Benign Prostatic Hyperplasia (enlarged prostate)

 Use:-

 The data in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The data  is not intended to cover all possible uses, directions, precautions, medicine  interactions or adverse effects, no should it be construed to indicate that use of a particular medicine  is safe, appropriate or effective for you or anyone else. A healthcare vocational should be consulted before taking any medicine, Exchange any diet or commencing or discontinuing any course of nursing.

 Dosage Instructions:-

 Missed Dose : If a dose of malegra 120mg 3ml tablet is missed, take the dose as soon as you remember

 Overdose : Seek emergency medical treatnmet or touch the doctor in case of an overdose.

 Interaction with Alcohol :Interaction with alcohol is unknown. It is suitable to consult your doctor before consumption.

 Interaction with Medicine: Allopurinol, Aliskiren, Insulin,Diclofenac,Candesartan,,Sacubitril/Valsartan

 How to take?

 ?        One should wash and dry his/her hands properly before taking this tablet.

 ?        One should take this tablet as long as directed by the physician.

 ?        Swallow it as a whole.

 How to work?

 Malegra 120, that contains Sildenafil Citrate, works by inhibiting the phosphodiesterase type 5 in the body.  It thus stops the degradation of cGMP (Cyclic Guanosine Monophosphate). Availability of cGMP helps relax the veins in penile region and thus aids erection when there is need for sexual activity or sexual stimulation.

 Inhibition of phosphodiesterase type 5 (PDE-5) in smooth muscle of pulmonary blood vessels results in its relaxation of the blood vessels and helps reduce the pressure in your lungs.

 Side effects:-

 Some patients may have allergic reactions. Inform your doctor if you have any signs of an allergic reaction like rash, itching, red-swollen skin, fever, trouble breathing, swollen face, etc.

 Chest pain or pressure

 A heartbeat that does not feel normal

 Dizziness or fainting

 Severe headache

 Weakness on one side of the body, trouble speaking or thinking, loss of balance, drooping on one side of the face, or blurred eyesight

 Change in eyesight

 Warning of capsule:-

 Hypotension- This medicine may cause hypotension, especially when used in combination with other high blood pressure medicines such as diuretics.

Aliskiren- Malegra 5 mg medicine  is not recommended for use in combination

with aliskiren due to the raised risk of serious side effects.

This risk is especially higher in diabetic patients.

Hyperkalemia-  This medicine may significantly increase the Potassium levels in the blood.

This may cause serious adverse effects.

 Storage:-

 Keep out of the reach and view of children. Do not store above 30 oC.Store in the original package, in order to protect from humidity. Do not use SILDENAFIL CITRATE after the expiry date which is stated on the carton. The expiry date refers to the last day of the month.tablets should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of pills no longer required. These measures will help to protect the environment.

                       For More Visit Click Here : Genericday.com 

[pediadoc7-blog]

Aliskiren Drug Information

Medical information for Aliskiren including Indication, Dosing, Adverse Effect. To know more about Aliskiren read this article https://www.pediatriconcall.com/drugs/aliskiren/241

[flowerbeetle13-blog]

Indicators on pyridium You Should Know

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[drugsyououghtaknow-blog]

Entresto

Active Ingredients: valsartan, sacubitril

Indications: reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.

TL;DR: (Read more details below the cut!)

Entresto is indicated for NYHA Class II-IV HFrEF (Heart Failure with Reduced Ejection Fraction) with EF (Ejection Fraction) ≤ 40%, based on clinical trial data. 

Entresto contains an ARB (Angiotensin Receptor Blocker), so you shouldn’t use it with another drug that works in this pathway (ACE inhibitors like lisinopril, other ARBs, and Renin Inhibitors like aliskiren) due to increased risk of angioedema and other side effects like hyperkalemia. 

Entresto has promising trial data suggesting that it may lower mortality in heart failure patients; however, Black patients only represented 5% of study participants and only 0.7% of patients included were NYHA Class IV.

This drug cannot be used in pregnant women.

Mechanism of Action: 

Sacubitril is a neprilysin inhibitor, which increases the levels of some natriuretic peptides that would normally be degraded by neprilysin.

Valsartan is an angiotensin receptor blocker, which selectively blocks the AT1 receptor and inhibits Angiotensin II-dependent aldosterone release.

Adverse Effects: (from clinical trial experience)

Hypotension (18%)

Hyperkalemia (12%)

Cough (9%)

Dizziness (6%)

Renal Failure/Acute Renal Failure (5%)

Contraindications: 

history of angioedema related to ACE inhibitor or ARB

concomitant use of ACE inhibitors (do not administer within 36 hours of an ACE inhibitor)

concomitant use of aliskiren in patients with diabetes

Clinical Trial Data: (Show me the receipts!)

PARADIGM-HF

Compared Entresto and enalapril in 8,442 adult patients with symptomatic chronic heart failure (NYHA class II–IV) and systolic dysfunction (left ventricular ejection fraction ≤ 40%). Patients had to have been on an ACE inhibitor or ARB for at least four weeks and on maximally tolerated doses of beta-blockers.

Patients with a systolic blood pressure of < 100 mmHg at screening were excluded.

The median follow-up duration was 27 months and patients were treated for up to 4.3 years.

Population used

66% Caucasian, 18% Asian, and 5% Black.

Mean age was 64 years

78% male.

70% of patients were NYHA Class II, 24% were NYHA Class III, and 0.7% were NYHA Class IV.

Mean EF 29%. 

The underlying cause of heart failure was coronary artery disease in 60% of patients.

71% had a history of hypertension

43% had a history of myocardial infarction

37% had an eGFR < 60 mL/min/1.73m2

35% had diabetes mellitus

Most patients were taking beta-blockers (94%), mineralocorticoid antagonists (58%), and diuretics (82%). 

Few patients had an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy-defibrillator (CRT-D) (15%).

In the Entresto group, 21.8% (914 patients) experienced  cardiovascular death or heart failure hospitalization, compared with 26.5% (1,117 patients) in the enalapril comparator group, with a p-value of < 0.0001.

When measuring all-cause mortality, 17.0% (711 patients) in the Entresto group had died compared to 19.8% (835 patients) in the enalapril comparator group, with a p-value of 0.0009.

For full labeling information, click here.

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New Post has been published on Pharmapedia

New Post has been published on http://pharmapedia.pw/2017/01/09/qbrelis-lisinopril-oral-solution/

Qbrelis | lisinopril - oral solution

Indications and Usage for Qbrelis

Hypertension

Qbrelis is indicated for the treatment of hypertension in adult patients and pediatric patients 6 years of age and older to lower blood pressure. Lowering blood pressure lowers the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes.

Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than 1 drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

Numerous antihypertensive drugs from a variety of pharmacologic classes and with different mechanisms of action have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.

Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.

Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in Black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.

Qbrelis may be administered alone or with other antihypertensive agents

Heart Failure

Qbrelis is indicated to reduce signs and symptoms of systolic heart failure

Reduction of Mortality in Acute Myocardial Infarction

Qbrelis is indicated for the reduction of mortality in treatment of hemodynamically stable patients within 24 hours of acute myocardial infarction. Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, aspirin and beta-blockers

Qbrelis Dosage and Administration

Hypertension

Adults

Initial Therapy in adults: The recommended initial dose is 10 mg taken orally once a day. Adjust dosage as needed according to blood pressure response. The usual dosage range is 20 to 40 mg per day administered in a single daily dose. Doses up to 80 mg per day have been used but do not appear to give greater effect.

Use with diuretics in adults

If blood pressure is not controlled with Qbrelis alone, a low dose of a diuretic may be added (e.g., hydrochlorothiazide, 12.5 mg). After the addition of a diuretic, it may be possible to reduce the dose of Qbrelis.

The recommended starting dose in adult patients with hypertension taking diuretics is 5 mg once per day.

Pediatric Patients 6 years of age and older with hypertension

For pediatric patients with glomerular filtration rate > 30 mL/min/1.73m2, the recommended starting dose is 0.07 mg per kg (up to 5 mg total) taken orally once daily. Dosage should be adjusted according to blood pressure response up to a maximum of 0.61 mg per kg (up to 40 mg) once daily. Doses above 0.61 mg per kg (or in excess of 40 mg) have not been studied in pediatric patients .

Qbrelis is not recommended in pediatric patients less than 6 years of age or in pediatric patients with glomerular filtration rate < 30 mL/min/1.73m2 .

Heart Failure

The recommended starting dose for Qbrelis, when used with diuretics and (usually) digitalis as adjunctive therapy for systolic heart failure, is 5 mg taken orally once daily. The recommended starting dose in these patients with hyponatremia (serum sodium < 130 mEq/L) is 2.5 mg once daily. Increase as tolerated to a maximum of 40 mg once daily.

Diuretic dose may need to be adjusted to help minimize hypovolemia, which may contribute to hypotension. The appearance of hypotension after the initial dose of Qbrelis does not preclude subsequent careful dose titration with the drug, following effective management of the hypotension.

Reduction of Mortality in Acute Myocardial Infarction

Initiation

In hemodynamically stable patients within 24 hours of the onset of symptoms of acute myocardial infarction, give Qbrelis 5 mg orally, followed by 5 mg after 24 hours, and then 10 mg once daily. Dosing should continue for at least six weeks. In patients with a low systolic blood pressure (≤ 120 mmHg and > 100 mmHg) during the first 3 days after the infarct initiate therapy with 2.5 mg once daily  and titrate up based on tolerability.

Maintenance

The usual maintenance dose is 10 mg once daily. If hypotension (systolic blood pressure ≤ 100 mmHg) occurs during maintenance treatment, give 5 mg once daily with temporary reductions to 2.5 mg if needed. If prolonged hypotension occurs (systolic blood pressure < 90 mmHg for more than 1 hour) Qbrelis should be withdrawn.

Dose in Patients with Renal Impairment

No dose adjustment of Qbrelis is required in patients with creatinine clearance > 30 mL/min. In patients with creatinine clearance ≥ 10 mL/min and ≤ 30 mL/min, reduce the initial dose of Qbrelis to half of the usual recommended dose, i.e., hypertension, 5 mg once daily; systolic heart failure, 2.5 mg once daily and acute myocardial infarction, 2.5 mg once daily. Up titrate as tolerated to a maximum of 40 mg daily. For patients on hemodialysis or creatinine clearance < 10 mL/min, the recommended initial dose is 2.5 mg once daily .

Dosage Forms and Strengths

Qbrelis oral solution is available in a 150 mL bottle containing 1 mg/mL of lisinopril solution. Qbrelis oral solution is a clear to slightly opalescent liquid.

Contraindications

Qbrelis is contraindicated in patients with:

•

a history of angioedema or hypersensitivity related to previous treatment with an angiotensin converting enzyme inhibitor

•

hereditary or idiopathic angioedema

Do not co-administer aliskiren with Qbrelis in patients with diabetes .

Warnings and Precautions

Fetal Toxicity

Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Qbrelis as soon as possible .

Angioedema and Anaphylactoid Reactions

Angioedema

Head and Neck Angioedema

Angioedema of the face, extremities, lips, tongue, glottis and/or larynx, including some fatal reactions, have occurred in patients treated with angiotensin converting enzyme inhibitors, including lisinopril, at any time during treatment. Patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially those with a history of airway surgery. Qbrelis should be promptly discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms of angioedema has occurred.

Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor . ACE inhibitors have been associated with a higher rate of angioedema in Black than in non-Black patients.

Patients receiving coadministration of an ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema.

Intestinal Angioedema

Intestinal angioedema has occurred in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. In some cases, the angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor.

Anaphylactoid Reactions

Anaphylactoid Reactions During Desensitization

Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions.

Anaphylactoid Reactions During Dialysis

Sudden and potentially life threatening anaphylactoid reactions have occurred in some patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. In such patients, dialysis must be stopped immediately, and aggressive therapy for anaphylactoid reactions must be initiated. Symptoms have not been relieved by antihistamines in these situations. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.

Impaired Renal Function

Monitor renal function periodically in patients treated with Qbrelis. Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, post-myocardial infarction or volume depletion) may be at particular risk of developing acute renal failure on Qbrelis. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on Qbrelis .

Hypotension

Qbrelis can cause symptomatic hypotension, sometimes complicated by oliguria, progressive azotemia, acute renal failure or death. Patients at risk of excessive hypotension include those with the following conditions or characteristics: heart failure with systolic blood pressure below 100 mmHg, ischemic heart disease, cerebrovascular disease, hyponatremia, high dose diuretic therapy, renal dialysis, or severe volume and/or salt depletion of any etiology.

In these patients, Qbrelis should be started under very close medical supervision and such patients should be followed closely for the first two weeks of treatment and whenever the dose of Qbrelis and/or diuretic is increased. Avoid use of Qbrelis in patients who are hemodynamically unstable after acute MI.

Symptomatic hypotension is also possible in patients with severe aortic stenosis or hypertrophic cardiomyopathy.

Surgery/Anesthesia

In patients undergoing major surgery or during anesthesia with agents that produce hypotension, Qbrelis 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.

Hyperkalemia

Serum potassium should be monitored periodically in patients receiving Qbrelis. Drugs that inhibit the renin-angiotensin system can cause hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements and/or potassium-containing salt substitutes .

Hepatic Failure

ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice or hepatitis and progresses to fulminant hepatic necrosis and sometimes death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical treatment.

Adverse Reactions

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Hypertension

In clinical trials in patients with hypertension treated with lisinopril, 5.7% of patients on lisinopril discontinued with adverse reactions.

The following adverse reactions (events 2% greater on lisinopril than on placebo) were observed with lisinopril alone: headache (by 3.8%), dizziness (by 3.5%), and cough (by 2.5%).

Heart Failure

In patients with systolic heart failure treated with lisinopril for up to four years, 11% discontinued therapy with adverse reactions. In controlled studies in patients with heart failure, therapy was discontinued in 8.1% of patients treated with lisinopril for 12 weeks, compared to 7.7% of patients treated with placebo for 12 weeks.

The following adverse reactions (events 2% greater on lisinopril than on placebo) were observed with lisinopril: hypotension (by 3.8%), and chest pain (by 2.1%).

In the two-dose ATLAS trial in heart failure patients, withdrawals due to adverse reactions were not different between the low and high dose groups, either in total number of discontinuation (17-18%) or in rare specific reactions (< 1%). The following adverse reactions, mostly related to ACE inhibition, were reported more commonly in the high dose group:

Table 1. Dose-related Adverse Drug Reactions: ATLAS trial

High Dose (n=1568)

Low Dose (n=1596)

Dizziness

19%

12%

Hypotension

11%

7%

Creatinine increased

10%

7%

Hyperkalemia

6%

4%

Syncope

7%

5%

Acute Myocardial Infarction

Patients treated with lisinopril had a higher incidence of hypotension (by 5.3%) and renal dysfunction (by 1.3%) compared with patients not taking lisinopril.

Other clinical adverse reactions occurring in 1% or higher of patients with hypertension or heart failure treated with lisinopril in controlled clinical trials and do not appear in other sections of labeling are listed below:

Body as a whole: Fatigue, asthenia, orthostatic effects.

Digestive: Pancreatitis, constipation, flatulence, dry mouth, diarrhea.

Hematologic: Rare cases of bone marrow depression, hemolytic anemia, leukopenia/neutropenia and thrombocytopenia.

Endocrine: Diabetes mellitus, inappropriate antidiuretic hormone secretion.

Metabolic: Gout.

Skin: Urticaria, alopecia, photosensitivity, erythema, flushing, diaphoresis, cutaneous pseudolymphoma, toxic epidermal necrolysis, Stevens – Johnson syndrome, and pruritus.

Special Senses: Visual loss, diplopia, blurred vision, tinnitus, photophobia, taste disturbances, olfactory disturbance.

Urogenital: Impotence.

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

Clinical Laboratory Test Findings

Serum Potassium: In clinical trials hyperkalemia (serum potassium greater than 5.7 mEq/L) occurred in 2.2% and 4.8% of lisinopril-treated patients with hypertension and heart failure, respectively .

Creatinine, Blood Urea Nitrogen: Minor increases in blood urea nitrogen and serum creatinine, reversible upon discontinuation of therapy, were observed in about 2% of patients with hypertension treated with lisinopril alone. Increases were more common in patients receiving concomitant diuretics and in patients with renal artery stenosis . Reversible minor increases in blood urea nitrogen and serum creatinine were observed in 11.6% of patients with heart failure on concomitant diuretic therapy. Frequently, these abnormalities resolved when the dosage of the diuretic was decreased.

Patients with acute myocardial infarction in the GISSI-3 trial treated with lisinopril had a higher (2.4% versus 1.1% in placebo) incidence of renal dysfunction in-hospital and at six weeks (increasing creatinine concentration to over 3 mg/dL or a doubling or more of the baseline serum creatinine concentration).

Hemoglobin and Hematocrit: Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.4 g% and 1.3 vol%, respectively) occurred frequently in patients treated with lisinopril but were rarely of clinical importance in patients without some other cause of anemia. In clinical trials, less than 0.1% of patients discontinued therapy due to anemia.

Post-marketing Experience

The following adverse reactions have been identified during post-approval use of lisinopril that are not included in other sections of labeling. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Other reactions include:

Metabolism and nutrition disorders

Hyponatremia , cases of hypoglycemia in diabetic patients on oral antidiabetic agents or insulin .

Nervous system and psychiatric disorders

Mood alterations (including depressive symptoms), mental confusion, hallucinations

Skin and subcutaneous tissue disorders

Psoriasis

Drug Interactions

Diuretics

Initiation of Qbrelis in patients on diuretics may result in excessive reduction of blood pressure. The possibility of hypotensive effects with Qbrelis can be minimized by either decreasing or discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with Qbrelis. If this is not possible, reduce the starting dose of Qbrelis .

Qbrelis attenuates potassium loss caused by thiazide-type diuretics. Potassium-sparing diuretics (spironolactone, amiloride, triamterene, and others) can increase the risk of hyperkalemia. Therefore, if concomitant use of such agents is indicated, monitor the patient’s serum potassium frequently.

Antidiabetics

Concomitant administration of Qbrelis and antidiabetic medicines (insulins, oral hypoglycemic agents) may cause an increased blood-glucose-lowering effect with risk of hypoglycemia.

Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors)

In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including lisinopril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving lisinopril and NSAID therapy.

The antihypertensive effect of ACE inhibitors, including lisinopril, may be attenuated by NSAIDs.

Dual Blockade of the Renin-Angiotensin System (RAS)

Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy.

The VA NEPHRON trial enrolled 1448 patients with type 2 diabetes, elevated urinary-albumin-to-creatinine ratio, and decreased estimated glomerular filtration rate (GFR 30 to 89.9 mL/min), randomized them to lisinopril or placebo on a background of losartan therapy and followed them for a median of 2.2 years. Patients receiving the combination of losartan and lisinopril did not obtain any additional benefit compared to monotherapy for the combined endpoint of decline in GFR, end stage renal disease, or death, but experienced an increased incidence of hyperkalemia and acute kidney injury compared with the monotherapy group.

In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on Qbrelis and other agents that affect the RAS.

Do not co-administer aliskiren with Qbrelis in patients with diabetes. Avoid use of aliskiren with Qbrelis in patients with renal impairment (GFR < 60 mL/min).

Lithium

Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs, which cause elimination of sodium, including ACE inhibitors. Lithium toxicity was usually reversible upon discontinuation of lithium and the ACE inhibitor. Monitor serum lithium levels during concurrent use.

Gold

Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including lisinopril.

mTOR Inhibitors

Patients taking concomitant mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema .

USE IN SPECIFIC POPULATIONS

Pregnancy

Risk Summary

Qbrelis can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. When pregnancy is detected, discontinue Qbrelis as soon as possible.

The estimated background risk of major birth defects and miscarriage for the indicated population(s) are unknown. In the general U.S. population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryo/fetal risk

Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly.

Fetal/Neonatal Adverse Reactions

Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia and skeletal deformations, including skull hypoplasia, hypotension, and death. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus.

Perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Qbrelis for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occur in neonates with a history of in utero exposure to Qbrelis, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and substituting for disordered renal function.

Lactation

Risk Summary

No data are available regarding the presence of lisinopril in human milk or the effects of lisinopril on the breastfed infant or on milk production. Lisinopril is present in rat milk. Because of the potential for severe adverse reactions in the breastfed infant, advise women not to breastfeed during treatment with Qbrelis.

Pediatric Use

Antihypertensive effects and safety of lisinopril have been established in pediatric patients aged 6 to 16 years . No relevant differences between the adverse reaction profile for pediatric patients and adult patients were identified.

Safety and effectiveness of lisinopril have not been established in pediatric patients under the age 6 or in pediatric patients with glomerular filtration rate < 30 mL/min/1.73 m2.

Neonates with a history of in utero exposure to Qbrelis

If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.

Geriatric Use

No dosage adjustment with Qbrelis is necessary in elderly patients. In a clinical study of lisinopril in patients with myocardial infarctions (GISSI-3 Trial), 4,413 (47%) were 65 and over, while 1,656 (18%) were 75 and over. In this study, 4.8 % of patients aged 75 years and older discontinued lisinopril treatment because of renal dysfunction vs. 1.3% of patients younger than 75 years. No other differences in safety or effectiveness were observed between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Race

ACE inhibitors, including Qbrelis, have an effect on blood pressure that is less in Black patients than in non-Blacks.

Renal Impairment

Dose adjustment of Qbrelis is required in patients undergoing hemodialysis or whose creatinine clearance is ≤ 30 mL/min. No dose adjustment of Qbrelis is required in patients with creatinine clearance > 30 mL/min .

Overdosage

Following a single oral dose of 20 g/kg no lethality occurred in rats, and death occurred in one of 20 mice receiving the same dose. The most likely manifestation of overdosage would be hypotension, for which the usual treatment would be intravenous infusion of normal saline solution.

Lisinopril can be removed by hemodialysis .

Qbrelis Description

Lisinopril is an oral long-acting angiotensin converting enzyme (ACE) inhibitor. Lisinopril is a synthetic peptide derivative that is manufactured as a dihydrate and is chemically described as 1-[N2-[(S)-1-Carboxy-3-phenylpropyl]-L-lysyl]-L-proline dihydrate. Its molecular formula is C21H31N3O5·2H2O and its structural formula is:

Lisinopril is a white to off-white, crystalline powder, with a molecular weight of 441.52 (for dihydrate). It is soluble in water, sparingly soluble in methanol, and practically insoluble in ethanol.

Qbrelis (lisinopril), 1 mg/mL, is a ready-to-use aqueous formulation. Each 1 mL of the oral solution contains 1.09 mg of lisinopril dihydrate, which is equivalent to 1 mg of lisinopril as the active ingredient and the following inactive ingredients: purified water, xylitol, sodium citrate, citric acid, sodium benzoate, and either hydrochloric acid or sodium hydroxide which may be added for pH adjustment. The solution is clear to slightly opalescent. Qbrelis is supplied as 150 mL of the solution packaged in a 150-mL round, white, opaque, high-density polyethylene (HDPE) bottle with a white, polypropylene, child-resistant closure with a heat induction layered inner seal.

Qbrelis – Clinical Pharmacology

Mechanism of Action

Lisinopril inhibits angiotensin-converting enzyme (ACE) in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. The beneficial effects of lisinopril in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system. Inhibition of ACE results in decreased plasma angiotensin II which leads to decreased vasopressor activity and to decreased aldosterone secretion. The latter decrease may result in a small increase of serum potassium. In hypertensive patients with normal renal function treated with lisinopril alone for up to 24 weeks, the mean increase in serum potassium was approximately 0.1 mEq/L; however, approximately 15% of patients had increases greater than 0.5 mEq/L and approximately 6% had a decrease greater than 0.5 mEq/L. In the same study, patients treated with lisinopril and hydrochlorothiazide for up to 24 weeks had a mean decrease in serum potassium of 0.1 mEq/L; approximately 4% of patients had increases greater than 0.5 mEq/L and approximately 12% had a decrease greater than 0.5 mEq/L . Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity.

ACE is identical to kininase, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of Qbrelis remains to be elucidated.

While the mechanism through which Qbrelis lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, Qbrelis is antihypertensive even in patients with low-renin hypertension. Although lisinopril was antihypertensive in all races studied, Black hypertensive patients (usually a low‑renin hypertensive population) had a smaller average response to monotherapy than non-Black patients.

Concomitant administration of lisinopril and hydrochlorothiazide further reduced blood pressure in Black and non-Black patients and any racial differences in blood pressure response were no longer evident.

Pharmacodynamics

Hypertension

Adult Patients: Administration of lisinopril to patients with hypertension results in a reduction of both supine and standing blood pressure to about the same extent with no compensatory tachycardia. Symptomatic postural hypotension is usually not observed although it can occur and should be anticipated in volume and/or salt-depleted patients . When given together with thiazide-type diuretics, the blood pressure lowering effects of the two drugs are approximately additive.

In most patients studied, onset of antihypertensive activity was seen at one hour after oral administration of an individual dose of lisinopril, with peak reduction of blood pressure achieved by 6 hours. Although an antihypertensive effect was observed 24 hours after dosing with recommended single daily doses, the effect was more consistent and the mean effect was considerably larger in some studies with doses of 20 mg or more than with lower doses; however, at all doses studied, the mean antihypertensive effect was substantially smaller 24 hours after dosing than it was 6 hours after dosing.

The antihypertensive effects of lisinopril are maintained during long-term therapy. Abrupt withdrawal of lisinopril has not been associated with a rapid increase in blood pressure, or a significant increase in blood pressure compared to pretreatment levels.

Non-Steroidal Anti-Inflammatory Agents

In a study in 36 patients with mild to moderate hypertension where the antihypertensive effects of lisinopril alone were compared lisinopril given concomitantly with indomethacin, the use of indomethacin was associated with a reduced effect, although the difference between the two regimens was not significant.

Pharmacokinetics

Adult Patients: Qbrelis is bioequivalent to lisinopril tablets under fasted and fed conditions.

Following oral administration of lisinopril tablets, peak serum concentrations of lisinopril occur within about 7 hours, although there was a trend to a small delay in time taken to reach peak serum concentrations in acute myocardial infarction patients. Food does not alter the bioavailability of lisinopril tablets. Declining serum concentrations exhibit a prolonged terminal phase, which does not contribute to drug accumulation. This terminal phase probably represents saturable binding to ACE and is not proportional to dose. Upon multiple dosing, lisinopril exhibits an effective half-life of 12 hours.

Lisinopril does not appear to be bound to other serum proteins. Lisinopril does not undergo metabolism and is excreted unchanged entirely in the urine. Based on urinary recovery, the mean extent of absorption of lisinopril is approximately 25%, with large intersubject variability (6‑60%) at all doses tested (5‑80 mg). The absolute bioavailability of lisinopril is reduced to 16% in patients with stable NYHA Class II-IV congestive heart failure, and the volume of distribution appears to be slightly smaller than that in normal subjects. The oral bioavailability of lisinopril in patients with acute myocardial infarction is similar to that in healthy volunteers.

Impaired renal function decreases elimination of lisinopril, which is excreted principally through the kidneys, but this decrease becomes clinically important only when the glomerular filtration rate is below 30 mL/min. Above this glomerular filtration rate, the elimination half-life is little changed. With greater impairment, however, peak and trough lisinopril levels increase, time to peak concentration increases and time to attain steady state is prolonged . Lisinopril can be removed by hemodialysis.

Pediatric Patients: The pharmacokinetics of lisinopril were studied in 29 pediatric hypertensive patients between 6 years and 16 years with glomerular filtration rate > 30 mL/min/1.73 m2. After doses of 0.1 to 0.2 mg per kg, steady state peak plasma concentrations of lisinopril occurred within 6 hours and the extent of absorption based on urinary recovery was about 28%. These values are similar to those obtained previously in adults. The typical value of lisinopril oral clearance (systemic clearance/absolute bioavailability) in a child weighing 30 kg is 10 L/h, which increases in proportion to renal function.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

There was no evidence of a tumorigenic effect when lisinopril was administered for 105 weeks to male and female rats at doses up to 90 mg per kg per day (about 56 or 9 times* the maximum recommended daily human dose, based on body weight and body surface area, respectively). There was no evidence of carcinogenicity when lisinopril was administered for 92 weeks to (male and female) mice at doses up to 135 mg per kg per day (about 84 times* the maximum recommended daily human dose). This dose was 6.8 times the maximum human dose based on body surface area in mice.

Lisinopril was not mutagenic in the Ames microbial mutagen test with or without metabolic activation. It was also negative in a forward mutation assay using Chinese hamster lung cells. Lisinopril did not produce single strand DNA breaks in an in vitro alkaline elution rat hepatocyte assay. In addition, lisinopril did not produce increases in chromosomal aberrations in an in vitro test in Chinese hamster ovary cells or in an in vivo study in mouse bone marrow.

There were no adverse effects on reproductive performance in male and female rats treated with up to 300 mg per kg per day of lisinopril. This dose is 188 times and 30 times the maximum human dose when based on mg/kg and mg/m2, respectively.

Studies in rats indicate that lisinopril crosses the blood brain barrier poorly. Multiple doses of lisinopril in rats do not result in accumulation in any tissues. Milk of lactating rats contains radioactivity following administration of 14C lisinopril. By whole body autoradiography, radioactivity was found in the placenta following administration of labeled drug to pregnant rats, but none was found in the fetuses.

*Calculations assume a human weight of 50 kg and human body surface area of 1.62m2.

Clinical Studies

Hypertension

Two dose-response studies utilizing a once-daily regimen were conducted in 438 mild to moderate hypertensive patients not on a diuretic. Blood pressure was measured 24 hours after dosing. An antihypertensive effect of lisinopril was seen with 5 mg of lisinopril in some patients. However, in both studies blood pressure reduction occurred sooner and was greater in patients treated with 10, 20 or 80 mg of lisinopril than patients treated with 5 mg of lisinopril.

In controlled clinical studies of patients with mild to moderate hypertension, patients were treated with lisinopril 20-80 mg daily, hydrochlorothiazide 12.5-50 mg daily or atenolol 50‑200 mg daily; and in other studies of patients with moderate to severe hypertension, patients were treated with lisinopril 20-80 mg daily or metoprolol 100-200 mg daily. Lisinopril demonstrated superior reductions of systolic and diastolic compared to hydrochlorothiazide in a population that was 75% Caucasian. Lisinopril was approximately equivalent to atenolol and metoprolol in reducing diastolic blood pressure, and had somewhat greater effects on systolic blood pressure.

Lisinopril had similar blood pressure reductions and adverse effects in younger and older (> 65 years) patients. It was less effective in reducing blood pressure in Blacks than in Caucasians.

In hemodynamic studies of lisinopril in patients with essential hypertension, blood pressure reduction was accompanied by a reduction in peripheral arterial resistance with little or no change in cardiac output and in heart rate. In a study in nine hypertensive patients, following administration of lisinopril, there was an increase in mean renal blood flow that was not significant. Data from several small studies are inconsistent with respect to the effect of lisinopril on glomerular filtration rate in hypertensive patients with normal renal function, but suggest that changes, if any, are not large.

In patients with renovascular hypertension lisinopril has been shown to be well-tolerated and effective in reducing blood pressure .

Pediatric Patients: In a clinical study involving 115 hypertensive pediatric patients 6 to 16 years of age, patients who weighed < 50 kg received either 0.625, 2.5 or 20 mg of lisinopril once daily and patients who weighed ≥ 50 kg received either 1.25, 5, or 40 mg of lisinopril once daily. At the end of 2 weeks, lisinopril lowered trough blood pressure in a dose-dependent manner with antihypertensive efficacy demonstrated at doses > 1.25 mg (0.02 mg per kg). This effect was confirmed in a randomized withdrawal phase, where the diastolic pressure rose by about 9 mmHg more in patients randomized to placebo than compared to patients who remained on the middle and high doses of lisinopril. The dose-dependent antihypertensive effect of lisinopril was consistent across several demographic subgroups: age, Tanner stage, gender, and race. In this study, lisinopril was generally well-tolerated.

In the above pediatric study, lisinopril was given either as tablets or in a suspension for those children who were unable to swallow tablets or who required a lower dose than is available in tablet form.

Heart Failure

Two placebo controlled, 12-week clinical studies compared the addition of lisinopril up to 20 mg daily to digitalis and diuretics alone. The combination of lisinopril, digitalis and diuretics reduced the following signs and symptoms of heart failure: edema, rales, paroxysmal nocturnal dyspnea and jugular venous distention. In one of the studies, the combination of lisinopril, digitalis and diuretics reduced orthopnea, presence of third heart sound and the number of patients classified as NYHA Class III and IV; and improved exercise tolerance. A large (over 3000 patients) survival study, the ATLAS Trial, comparing 2.5 and 35 mg of lisinopril in patients with systolic heart failure, showed that the higher dose of lisinopril had outcomes at least as favorable as the lower dose.

During baseline-controlled clinical trials, in patients with systolic heart failure receiving digitalis and diuretics, single doses of lisinopril resulted in decreases in pulmonary capillary wedge pressure, systemic vascular resistance and blood pressure accompanied by an increase in cardiac output and no change in heart rate.

Acute Myocardial Infarction

The Gruppo Italiano per lo Studio della Sopravvienza nell’Infarto Miocardico (GISSI-3) study was a multicenter, controlled, randomized, unblinded clinical trial conducted in 19,394 patients with acute myocardial infarction (MI) admitted to a coronary care unit. It was designed to examine the effects of short-term (6 week) treatment with lisinopril, nitrates, their combination, or no therapy on short-term (6 week) mortality and on long-term death and markedly impaired cardiac function. Hemodynamically-stable patients presenting within 24 hours of the onset of symptoms were randomized, in a 2 x 2 factorial design, to six weeks of either 1) lisinopril alone (n=4841), 2) nitrates alone (n=4869), 3) lisinopril plus nitrates (n=4841), or 4) open control (n=4843). All patients received routine therapies, including thrombolytics (72%), aspirin (84%), and a beta blocker (31%), as appropriate, normally utilized in acute myocardial infarction (MI) patients.

The protocol excluded patients with hypotension (systolic blood pressure ≤ 100 mmHg), severe heart failure, cardiogenic shock, and renal dysfunction (serum creatinine > 2 mg per dL and/or proteinuria > 500 mg per 24 h). Patients randomized to lisinopril received 5 mg within 24 hours of the onset of symptoms, 5 mg after 24 hours, and then 10 mg daily thereafter. Patients with systolic blood pressure less than 120 mmHg at baseline received 2.5 mg of lisinopril. If hypotension occurred, the lisinopril dose was reduced or if severe hypotension occurred lisinopril was stopped .

The primary outcomes of the trial were the overall mortality at 6 weeks and a combined end point at 6 months after the myocardial infarction, consisting of the number of patients who died, had late (day 4) clinical congestive heart failure, or had extensive left ventricular damage defined as ejection fraction ≤ 35% or an akinetic-dyskinetic [A-D] score ≥ 45%. Patients receiving lisinopril (n=9646), alone or with nitrates, had an 11% lower risk of death (p = 0.04) compared to patients who did not receive lisinopril (n=9672) (6.4% vs. 7.2%, respectively) at six weeks. Although patients randomized to receive lisinopril for up to six weeks also fared numerically better on the combined end point at 6 months, the open nature of the assessment of heart failure, substantial loss to follow-up echocardiography, and substantial excess use of lisinopril between 6 weeks and 6 months in the group randomized to 6 weeks of lisinopril, preclude any conclusion about this end point.

Patients with acute myocardial infarction, treated with lisinopril, had a higher (9.0% versus 3.7%) incidence of persistent hypotension (systolic blood pressure < 90 mmHg for more than 1 hour) and renal dysfunction (2.4% versus 1.1%) in-hospital and at six weeks (increasing creatinine concentration to over 3 mg per dL or a doubling or more of the baseline serum creatinine concentration) .

How Supplied/Storage and Handling

Qbrelis (lisinopril), 1 mg/mL, is supplied as 150 mL of a clear to slightly opalescent, colorless aqueous oral solution with a sweet taste in a 150-mL high-density polyethylene (HDPE) bottle with a child‑resistant cap (NDC 52652-3001-1).

Store at controlled room temperature 20°C‑25°C (68°F‑77°F) [see USP] in a tightly closed container. Protect from freezing and excessive heat.

Patient Counseling Information

Pregnancy: Tell female patients of childbearing age about the consequences of exposure to Qbrelis during pregnancy. Discuss treatment options with women planning to become pregnant. Tell patients to report pregnancies to their physicians as soon as possible.

Angioedema: Angioedema, including laryngeal edema may occur at any time during treatment with angiotensin converting enzyme inhibitors, including Qbrelis. Tell patients to report immediately any signs or symptoms suggesting angioedema (swelling of face, extremities, eyes, lips, tongue, difficulty swallowing or breathing) and to take no more drug until they have consulted with the prescribing physician.

Symptomatic Hypotension: Tell patients to report light-headedness especially during the first few days of therapy. If actual syncope occurs, tell the patient to discontinue the drug until they have consulted with the prescribing physician.

Tell patients that excessive perspiration and dehydration may lead to an excessive fall in blood pressure because of reduction in fluid volume. Other causes of volume depletion such as vomiting or diarrhea may also lead to a fall in blood pressure; advise patients accordingly.

Hyperkalemia: Tell patients to consult their physician prior to using salt substitutes containing potassium.

Hypoglycemia: Tell diabetic patients treated with oral antidiabetic agents or insulin starting an ACE inhibitor to monitor for hypoglycemia closely, especially during the first month of combined use .

Leukopenia/Neutropenia: Tell patients to report promptly any indication of infection (e.g., sore throat, fever), which may be a sign of leukopenia/neutropenia.

Manufactured for: Silvergate Pharmaceuticals, Inc. 6251 Greenwood Plaza Blvd., Suite 101 Greenwood Village, CO 80111

LI-1607

07/2016

[siglerprescriptiondrugcards]

Valsartan

Brand Name: Diovan

Generic Available

Common Dosage Forms:

Tablets: 40 mg, 80 mg, 160 mg, 320 mg

FDA Indications/Dosages:

For the treatment of hypertension when used alone or in combination with other antihypertensive agents: The recommended starting dose is 80 mg once daily in patients who are not volume depleted. The maintenance dosage range is 80-320 mg given once daily. The antihypertensive effect is substantially present within 2 weeks and maximal reduction is generally attained after 4 weeks. The addition of a diuretic has a greater effect than dose increases beyond 80 mg.

For the treatment of heart failure (NYHA Class II-IV) in patients who are intolerant of angiotensin-converting enzyme inhibitors: The recommended starting dose is 50 mg twice daily. Titration to 80-160 mg twice daily should be done to the highest dose, as tolerated by the patient.

To reduce cardiovascular mortality following myocardial infarction in patient with left ventricular failure or dysfunction: Start with 20 mg given twice daily. Titrate to 160 mg twice daily as tolerated by the patient.

Monitor: CrCl, BP, K

Pharmacology/Pharmacokinetics: Angiotensin II is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Valsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues. Valsartan peak plasma concentration is reached in 2-4 hours after an oral dose. Elimination half-life is about 6 hours. Food decreases absorption and peak plasma concentration by about 50%. Elimination occurs primarily as unchanged drug in the feces (83%) and urine (13%).

Drug Interactions: NSAIDs, including COX-2 inhibitors, may decrease effects and increase risk of renal function deterioration. Increased adverse effects may occur when used with other renin-angiotensin system blockers or aliskiren.

Contraindications/Precautions: Contraindicated with aliskiren. DO NOT USE DURING PREGNANCY. Use with caution in nursing mothers. Valsartan has been shown to be excreted in the milk of lactating rats. Use with caution in volume-depleted patients due to excessive hypotension. Use with caution in patients with impaired hepatic or renal function. Pregnancy Category D.

Adverse Effects: Generally well-tolerated with the most common adverse effects of headache and dizziness occurring at the same rate in patients receiving placebo.

Patient Consultation:

May be taken with or without food, although it may be best to administer without food for consistent plasma levels.

When pregnancy is detected, discontinue use as soon as possible.

Store in a cool, dry place away from sunlight and children.

Dizziness may occur during the first few days of treatment, report to a physician if this adverse effect persists.

Contact a physician if the above side effects are severe or persistent.

[siglerprescriptiondrugcards]

Ramipril

Brand Name: Altace

Generic Available

Common Dosage Forms:

Capsules: 1.25 mg, 2.5 mg, 5 mg, 10 mg

FDA Indications/Dosages:

For the treatment of hypertension, alone or in combination with thiazide diuretics: Initially give 2.5 mg once daily. Maintenance dose is between 2.5-20 mg/day in one or two doses.

Initial dose when using diuretics: Begin with 1.26 mg daily or temporarily discontinue diuretic therapy beginning 3 days before initial dose.

Reduction in the risk of myocardial infarction, stroke, and death from cardiovascular causes: Begin with 2.5 mg for 7 days, increase to 5 mg for 21 days, then adjust dose as tolerated.

Treatment of heart failure in post-MI patients: Begin with 2.5 mg twice a day.

Dosing in renal function impairment: Give 1.25 mg to a maximum of 5 mg daily in patients with CrCl of <40 mL/min/1.73m^2.

Monitor: K, BP, CrCl, WBC

Pharmacology/Pharmacokinetics: Ramipril’s mechanism of action is thought to be due to its suppression of the renin-aldosterone system by competitively inhibiting the angiotensin-converting enzyme (ACE). ACE converts angiotensin I to angiotensin II, one of the most potent vasoconstrictors known. Inhibition of ACE decreases plasma angiotensin II which leads to decreased aldosterone secretion. The latter may cause an increase in serum potassium. The net result is a decrease in peripheral arterial resistance. Ramipril is metabolized to the more active ramiprilat in the liver. Peak plasma levels of ramiprilat are reached in 2-4 hours. Protein binding is approximately 60%. Half-life of ramiprilat is 13-17 hours. Elimination occurs through the urine (60%) and the feces (40%).

Drug Interactions: Indomethacin may decrease therapeutic effects. Capsaicin may increase the incidence of coughing. Because of potassium-sparing effect, use caution when given with potassium-sparing diuretics and potassium supplements. Lithium toxicity may occur. Increased adverse effects may occur when used with other renin-angiotensin system blockers or aliskiren.

Contraindications/Precautions: Contraindicated in combination with neprilysin inhibitor (sacubitril). DO NOT USE DURING PREGNANCY. Use with caution in nursing mothers, in patients with impaired renal function, collagen vascular disease (may cause agranulocytosis), or aortic stenosis, and in patients undergoing surgery or anesthesia. Rare occurrences of angioedema and neutropenia have been seen in patients taking ACE inhibitors. Patients should report to their physician any signs of facial swelling, difficulty in breathing, or infection (unexplained fever or sore throat). Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice or hepatitis and progresses to fulminant hepatic necrosis and sometimes death. Pregnancy Category D.

Adverse Effects: Mild adverse effects include cough, headache, dizziness, and fatigue. A potentially serious side effect is angioedema.

Patient Consultation:

Do not discontinue medication unless otherwise directed by your physician.

Capsules may be swallowed whole, or their contents sprinkled over soft food and consumed (without chewing). They also may be mixed into water or apple juice and consumed. Pre-mixed solutions are stable for 24 hours at room temperature and 48 hours under refrigeration.

Avoid nonprescription cough, cold, and allergy medications unless otherwise directed.

Avoid salt substitutes containing potassium.

Report any signs of facial swelling, difficulty in breathing, or infection (unexplained fever or sore throat) to your physician.

Store in a cool, dry place away from sunlight and children.

If a dose is missed, take it as soon as possible. If it is closer to the time of your next dose than the dose you missed, skip the missed dose and return to your dosing schedule. Do not double doses.

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Olmesartan Medoxomil

Brand Name: Benicar

Generic Available

Common Dosage Forms:

Tablets: 5 mg, 20 mg, 40 mg

FDA Indications/Dosages:

For the treatment of hypertension: The usual recommended starting dose is 20 mg once daily when used as monotherapy in patients who are not volume-depleted. For patients requiring further reduction in blood pressure after 2 weeks of therapy, the dose may be increased to 40 mg once daily. A lower starting dose should be considered in patients with possible depletion of intravascular volume (e.g., patients treated with diuretics, particularly with impaired renal function). No initial dosage adjustment is recommended for elderly patients, for patients with moderate to marked renal impairment (CrCl <40 mL/min), or with moderate to marked hepatic dysfunction.

Monitor: CrCl, BP, K

Pharmacology/Pharmacokinetics: Angiotensin II is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Olmesartan medoxomil is a prodrug which is hydrolyzed to Olmesartan during absorption from the gastrointestinal tract. Olmesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues. Olmesartan does not inhibit ACE, nor does it bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation. Once absorbed, there is virtually no further metabolism of Olmesartan. The terminal half-life of Olmesartan is about 13 hours. Mean peak concentrations are reached in 1-2 hours. It is highly bound (99%) to plasma proteins.

Drug Interactions: NSAIDs, including COX-2 inhibitors, may decrease effects and increase risk of renal function deterioration. Increased adverse effects may occur when used with other renin-angiotensin system blockers or aliskiren. Colesevelam HCl decreases plasma levels.

Contraindications/Precautions: Contraindicated with aliskiren. DO NOT USE DURING PREGNANCY. Do not use in nursing mothers. Drugs that act directly on the renin-angiotensin system can cause fatal and neonatal morbidity and death when administered to pregnant women. In patients who are intravascularly volume-depleted, symptomatic hypotension may occur after initiation of therapy. A lower dose should be considered for these patients. Pregnancy Category D.

Adverse Effects: The most common adverse effect seen during therapy is dizziness (3%). Less common adverse effects include back pain, bronchitis, creatine phosphokinase increased, diarrhea, headache, hematuria, hyperglycemia, hypertriglyceridemia, influenza-like symptoms, pharyngitis, rhinitis, and sinusitis.

Patient Consultation:

May be administered with or without food.

May cause dizziness. Use care when operating machinery.

If pregnancy is directed, discontinue use as soon as possible.

Store in a cool, dry place away from sunlight and children.

Contact a physician if the above side effects are severe or persistent.

[siglerprescriptiondrugcards]

Losartan Potassium with Hydrochlorothiazide

Brand Name: Hyzaar

Generic Available

Common Dosage Forms:

Each 50-12.5 tablet contains 50 mg of losartan potassium and 12.5 mg hydrochlorothiazide

Each 100-12.5 tablet contains 100 mg of losartan potassium and 12.5 mg hydrochlorothiazide

Each 100-25 tablet contains 100 mg of losartan potassium and 25 mg hydrochlorothiazide

FDA Indications/Dosages:

Indicated for the treatment of hypertension: The usual dose is one tablet once daily. The maximal antihypertensive effect is attained about 3 weeks after initiation of therapy. To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with mono-therapy. The exception to this is when hypertension is severe enough that rapid control of hypertension is needed. The usual starting dose is 50 mg of losartan once daily, with 25 mg used in patients with possible depletion of intravascular volume. Losartan can be administered once or twice daily with total daily doses ranging from 25-100 mg. If the antihypertensive effect measured at trough using once-a-day dosing is inadequate, a twice-a-day regimen at the same total daily dose or an increase in dose may give a more satisfactory response. Hydrochlorothiazide is effective in doses of 12.5-100 mg once daily and can be given at doses of 12.5-25 mg in this combination.

Monitor: CrCl, BP, K

Pharmacology/Pharmacokinetics: Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the ATI receptor found in many tissues. Losartan is an orally active agent that undergoes substantial first-pass metabolism by cytochrome P450 enzymes. It is converted, in part, to an active carboxylic acid metabolite that is responsible for most of the angiotensin II receptor antagonism that follows losartan treatment. The terminal half-life of losartan is about 2 hours and of the metabolite is about 6-9 hours. Mean peak concentrations of losartan and its active metabolite are reached in 1 hour and 3-4 hours, respectively. Both losartan and its active metabolite are highly bound to plasma proteins, primarily albumin. Hydrochlorothiazide inhibits the reabsorption of sodium and chloride at the distal renal tubule. It reaches peak plasma levels in 4 hours with a half-life of 6-15 hours. Excretion of unchanged drug occurs in the urine.

Drug Interactions: Cimetidine may increase plasma levels of losartan. Phenobarbital may lower plasma levels of losartan. Hydrochlorothiazide may decrease sulfonylurea hypoglycemia. Electrolyte disturbances may cause DIGITALIS-induced arrhythmias. Use with diazoxide may cause hypoglycemia. May increase lithium serum levels. NSAIDs, including COX-2 inhibitors, can reduce the diuretic, natriuretic, and antihypertensive effects of this combination. Use with alcohol, barbiturates, or narcotics may potentiate orthostatic hypotension. Cholestyramine and colestipol resins may reduce absorption by up to 85% and 43% respectively. When used with corticosteroids or ACTH intensified electrolyte depletion may occur, particularly hypokalemia. Increased adverse effects may occur with other renin-angiotensin system blockers or aliskiren.

Contraindications/Precautions: Contraindicated with aliskiren. DO NOT USE DURING PREGNANCY. Use with caution in nursing mothers. In patients who are intravascularly volume-depleted, symptomatic hypotension may occur after initiation of therapy with this combination. A lower dose of losartan should be considered for patients with impaired liver function. Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. 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. Use with caution in patients with impaired renal function. Thiazides may exacerbate or activate systemic lupus erythematosus. Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals. Use with caution in patients with gout, diabetes, and in patients who are taking corticosteroids or ACTH. Pregnancy Category D.

Adverse Effects: The most common adverse effects are upper respiratory infection, dizziness, cough, and back pain. Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers.

Patient Consultation:

May be administered with or without food.

Store in a cool, dry place away from sunlight and children.

Contact a physician if the above side effects are severe or persistent.

Timing of dose is important because of increased diuresis. Usually given in early a.m.

Avoid excessive exposure to sunlight.

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Losartan Potassium

Brand Name: Cozaar

Generic Available

Common Dosage Forms:

Tablets: 25 mg, 50 mg, 100 mg

FDA Indications/Dosage Ranges:

Treatment of hypertension: The usual starting dose is 50 mg once daily, with 25 mg used in patients with possible depletion of intravascular volume. Con be administered once or twice daily with total daily doses ranging from 25-100 mg. If the antihypertensive effect measured at trough using once-a-day dosing is inadequate, a twice-a-day regimen at the same total dose or an increase in dose may be give a more satisfactory response. If blood pressure is not controlled by losartan alone, a low dose diuretic may be added.

To reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy*: Start with 50 mg once daily. Based on blood pressure response, add hydrochlorothiazide (HCTZ) or increase to 100 mg per day followed by an increase in HCTZ to 25 mg once daily.

For the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria (>300 mg/day) in patients with type 2 diabetes and hypertension: Start with 50 mg once daily. Increase to 100 mg once daily based on blood pressure response.

Monitor: CrCl, BP, K

Pharmacology/Pharmacokinetics: Angiotensin II is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the ATI receptor found in many tissues. The active metabolite is 10-40 times more potent by weight than losartan and appears to be a reversible, non-competitive inhibitor of the ATI receptor. Losartan is an orally active agent that undergoes substantial first-pass metabolism by cytochrome P450 enzymes. The terminal half-life of losartan is about 2 hours and of the active metabolite is about 6-9 hours. Mean peak concentrations of losartan and its active metabolite are reached in 1 hour and 3-4 ours, respectively. Both losartan and its active metabolite are highly bound to plasma proteins, primarily albumin.

Drug Interactions: Although not considered significant pharmacokinetic interactions, the following have been reported. Coadministration of cimetidine has led to an increase of about 18% in AUC of losartan but did not affect the pharmacokinetics of its active metabolite. Coadministration of phenobarbital led to a reduction of about 20% in the AUC of losartan and that of its active metabolite. NSAIDs, including COX-2 inhibitors, may decrease effects and increase risk of renal function deterioration. Increased adverse effects may occur when used with other renin-angiotensin system blockers or aliskiren.

Contraindications/Precautions: Contraindicate with aliskiren. DO NOT USE DURING PREGNANCY. Use with caution in nursing mothers. Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women. In patients who are intravascularly volume-depleted, symptomatic hypotension may occur after initiation of therapy with losartan. A lower dose should be considered for patients with impaired liver function. Pregnancy Category D.

Adverse Effects: The most common adverse effects are upper respiratory infection, diarrhea, dizziness, nasal congestion, and cough. Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers.

Patients Consultation:

May be administered with or without food.

When pregnancy is detected, losartan should be discontinued as soon as possible.

Store in a cool, dry place away from sunlight and children.

If a dose is missed, skip it and return to normal dosing schedule.

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Lisinopril with Hydrochlorothiazide

Brand Names: Zestoretic, Prinzide

Generic Available

Common Dosage Forms:

10-12.5 Tablets: Each tablet contains lisinopril 10 mg and hydrochlorothiazide 12.5 mg

20-12.5 Tablets: Each tablet contains lisinopril 20 mg and hydrochlorothiazide 12.5 mg

20-25 Tablets: Each tablet contains lisinopril 20 mg and hydrochlorothiazide 25 mg

FDA Indications/Dosages:

Treatment of hypertension: This fixed-dose combination drug is not indicated for initial treatment of hypertension. The normal dose is one tablet daily. The effective dose for lisinopril is 10-80 mg per day and for hydrochlorothiazide is 6.25-100 mg per day. A patient whose blood pressure is not adequately controlled with either lisinopril or hydrochlorothiazide monotherapy may be switched to lisinopril/HCTZ 10/12.5 or lisinopril/HCTZ 20/12.5, depending on current monotherapy dose.

Monitor: K, BP, CrCl, WBC

Pharmacology/Pharmacokinetics: Lisinopril’s effectiveness can be attributed to a number of different actions, most related to suppression of the renin-angiotensin-aldosterone system. Lisinopril competitively inhibits angiotensin-converting enzyme (ACE). Inhibition of this enzyme results in decreased synthesis of angiotensin II, one of the most potent vasoconstrictors known. The reduction in angiotensin II also decreases the release of aldosterone, which in turn decreases sodium and water reabsorption and lowers plasma volume. ACE is also involved with the degradation of bradykinin, a vasodilator. Peak serum levels are reached within 7 hours and the effective half-life is 12 hours. Lisinopril is not bound to plasma proteins. Lisinopril is not metabolized and is excreted in the urine. Hydrochlorothiazide inhibits the reabsorption of sodium and chloride at the distal renal tubule. It reaches peak plasma levels in 4 hours with a half-life of 6-15 hours. Excretion of unchanged drug occurs in the urine.

Drug Interactions: The pharmacological effect is decreased when used with indomethacin. A higher risk of hypersensitivity reaction occurs when used with allopurinol. Use with potassium supplements may cause hyperkalemia. Electrolyte disturbances may cause DIGITALIS-induced arrhythmias. Use with diazoxide may cause hyperglycemia. May increase lithium serum levels. Increased adverse effects may occur when used with other renin-angiotensin system blockers or aliskiren.

Contraindications/Precautions: Contraindicated in patients with a history of angioedema related to a previous treatment with an angiotensin-converting enzyme inhibitor and in patients with anuria or who are hypersensitive to sulfonamide-derived drugs. DO NOT USE DURING PREGNANCY. Use with caution in patients who cirrhosis, gout, impaired renal or hepatic function, diabetes, and in patients who are taking corticosteroids or ACTH. Risk for potentially serious hyperkalemia is increased with use of potassium-sparing drugs, potassium supplements, diabetes mellitus, and impaired renal function. Hypoglycemia may occur when therapy is added to patients taking oral antidiabetics and/or insulin. Angioedema and/or severe hypotension may warrant discontinuance of medication. Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice or hepatitis and progresses to fulminant hepatic necrosis and sometimes death. Pregnancy Category D.

Adverse Effects: Dizziness (6%), headache (5%), fatigue (3%), cough (3%), and diarrhea (3%). A potentially severe adverse effect is angioedema.

Patient Consultation:

May be taken without regard to meals.

Timing of dose is important because of increased diuresis. Usually given in early a.m.

Avoid excessive exposure to sunlight.

Do not discontinue medication unless otherwise directed by your physician.

Avoid nonprescription cough, cold, and allergy medications unless otherwise directed.

Avoid salt substitutes containing potassium.

Store in a cool, dry place away from sunlight and children.

If a dose is missed, take it as soon as possible. If it is closer to the time of your next dose than the dose you missed, skip the missed dose and return to your dosing schedule. Do not double doses.

Contact a physician if the above side effects are severe or persistent.

Contact a physician if signs of swelling occur.

[siglerprescriptiondrugcards]

Irbesartan

Brand Name: Avapro

Generic Available

Common Dosage Forms:

Tablets: 75 mg, 150 mg, 300 mg

FDA Indications/Dosages:

For the treatment of hypertension: Recommended initial dose is 150 mg once daily. Patients requiring further reduction in blood pressure should be titrated to 300 mg once daily. Irbesartan may be used alone or in combination with other antihypertensive agents. No dosage adjustment is necessary in elderly patients, or in patients with hepatic impairment or mild to severe renal impairment. Avapro may be administered with or without food.

For the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria (>300 mg/day) in patients with type 2 diabetes and hypertension: The recommended target dose is 300 mg once daily.

Pharmacology/Pharmacokinetics: Angiotensin II is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Irbesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues. Irbesartan does not inhibit ACE, bind to, or block other hormone receptors of ion channels known to be important in cardiovascular regulation. After an oral dose, irbesartan is rapidly absorbed with an average absolute bioavailability of 60-80%. Peak plasma levels are reached in 1.5-2 hours. Terminal elimination half-life averages 11-15 hours with steady state levels reached in 3 days. Metabolism occurs via glucuronide conjugation and oxidation (2C9). Irbesartan is 90% bound to serum proteins.

Drug Interactions: NSAIDs, including COX-2 inhibitors, may decrease effects and increase risk of renal function deterioration. Increased adverse effects may occur when used with other renin-angiotensin system blockers or aliskiren.

Contraindications/Precautions: Contraindicated with aliskiren. DO NOT USE DURING PREGNANCY. Do not use in nursing mothers. Use with caution in patients whose renal function may be dependent on the activity of the renin-angiotensin-aldosterone system, such as those with congestive heart failure. Rare cases of oliguria and/or progressive azotemia resulting in renal failure or death have occurred in patients receiving angiotensin converting enzyme inhibitors and angiotensin receptor antagonists. Patients should have intravascular sodium- and volume- depletion corrected prior to initiation of therapy or the initial dose should be lowered. Pregnancy Category D.

Adverse Effects: Mild adverse effects include upper respiratory tract infection (9%), fatigue (4%), diarrhea (3%), dyspepsia/heartburn (2%), and musculoskeletal trauma (2%).

Patient Consultation:

May be administered with or without food.

When pregnancy is detected, discontinue drug as soon as possible.

Store in a cool, dry place away from sunlight and children.

Contact a physician if the above side effects are severe or persistent.

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Fosinopril Sodium

Brand Name: Monopril

Generic Available

Common Dosage Forms:

Tablets: 10 mg, 20 mg, 40 mg

FDA Indications/Dosages:

For the treatment of hypertension, alone or in combination with thiazide diuretics: Initially give 10 mg daily. Maintenance dose is between 20 mg and 80 mg/day in one to two doses.

Initial dose when using diuretics: Bein with 10 mg daily or temporarily discontinue diuretic therapy beginning 3 days before initial dose.

Management of heart failure as adjunctive therapy when added to conventional therapy including diuretics or digitalis: Start with 10 mg daily. Titrate to a maximum of 40 mg daily.

No dosage adjustment is necessary in renal impairment.

Monitor: K, BP, CrCL, WBC

Pharmacology/Pharmacokinetics: Fosinopril is hydrolyzed to fosinoprilat which suppresses the renin-angiotensin-converting enzyme (ACE). ACE converts angiotensin I to angiotensin II, one of the most potent vasoconstrictors known. Inhibition of ACE decreases plasma angiotensin II which leads to decreased aldosterone secretion, The latter may cause a decrease in serum potassium. The net result is a decrease in peripheral arterial resistance. Peak plasma levels of fosinoprilat are reached in 3 hours. Protein binding is ≥95%. Half-life of fosinoprilat is 11.5 hours. Elimination occurs through the urine (50%) and the feces (50%).

Drug Interactions: Antacids decrease absorption. Indomethacin may decrease therapeutic effects. Capsaicin may increase the incidence of coughing. Because of potassium-sparing effect, use caution with potassium-sparing diuretics and potassium supplements. Lithium toxicity may occur. May cause a false low digoxin using Digi-Tab RIA Kit. Increased adverse effects may occur when used with other renin-angiotensin system blockers or aliskiren.

Contraindications/Precautions: Contraindicated in combinations with neprilysin inhibitor (sacubitril). DO NOT USE DURING PREGNANCY. Use with caution in nursing women, in patients with impaired renal function, collagen vascular disease (may cause agranulocytosis), or aortic stenosis, and in patients undergoing surgery or anesthesia. Rare occurrences of angioedema and neutropenia have been seen in patients taking ACEIs. Patients should report to their physician and sign  of facial swelling, difficulty in breathing, or infection (unexplained fever, or sore throat). Pregnancy Category D.

Adverse Effects: Mild adverse effects include cough, headache, dizziness, diarrhea, and fatigue. A potentially serious adverse effect is angioedema.

Patient Consultation:

Do not take antacids within 1-2 hours of taking medication.

Do not discontinue medications unless otherwise directed by your physician.

Avoid nonprescription cough, cold, and allergy medications unless otherwise directed.

Avoid salt substitutes containing potassium.

Report any sign of facial swelling, difficulty in breathing, or infection (fever, sore throat) to your physician.

Store in a cool, dry place away from sunlight and children.

If a dose is missed, take it as soon as possible. If it is closer to the time of your next dose than the dose you missed, skip the missed dose and return to your dosing schedule. Do not double doses.

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Enalapril Maleate

Common Brand Names: Vasotec, Epaned

Generic Available

Common Dosage Forms:

Tablet: 2.5 mg, 5 mg, 10 mg, and 20 mg

Powder for Oral Solution (Epaned): 1 mg/mL after reconstitution

Injection: 1.25 mg enalaprilat in 1 and 2 mL vials

FDA Indications/Precaution:

In the treatments hypertension: Oral: In patients currently taking a diuretic, symptomatic hypotension may occur following the initial dose of enalapril. Therefore, the diuretic should be discontinued two to three days before beginning therapy with enalapril. If the diuretic cannot be discontinued, an initial dose of 2.5 mg should be used to test for significant first-dose hypotension. The usual dosage range is 5-40 mg per day in a single or divided dose (for those patients where the antihypertensive effect diminishes at the end of the dosing interval). Injectable: The starting dose should be 1.25 mg every 6 hours IV over 5 minutes. Patients should be converted to the oral form as soon as possible.

Treatment of congestive heart failure (oral route only): Initially 2.5 mg once or twice daily in conjunction with diuretics and digitalis. Normal maintenance dose is 5-20 mg daily given in two divided doses.

Asymptomatic left ventricular dysfunction (oral route only): Initially 2.5 mg twice daily. Titrate as tolerated to 20 mg daily in divided doses.

Dosage adjustment in Renal Impairment (CrCL <30 mL/min): The initial oral dose should be 2.5 mg adjusted upward until blood pressure is controlled or to a maximum of 40 mg per day. Initial IV dose should be 0.625 mg over 5 minutes and repeated in one hour. Use 1.25 mg every 6 hours thereafter.

Monitor: K, BP, CrCL, WBC

Pharmacology/Pharmacokinetics: Enalapril undergoes hydrolysis after absorption to form the active metabolite enalapril. Enalapril’s effectiveness can be attributed to a number of different actions, most related to a suppression of the renin-angiotensin-converting (ACE), which results in a decreased synthesis of angiotensin II, one of the most potent vasoconstrictors known. The reduction in angiotensin II also decreases the release of aldosterone, which in turn decreases the sodium and water reabsorption and lowers plasma volume. The result is a reduction of peripheral arterial resistance and an increase in cardiac output. ACE is also involved with the degradation of bradykinin, a vasodilator. Peak serum levels of enalaprilat occur 3 hours after an oral dose and its effective half-life is 11 hours.

Drug Interactions: Indomethacin may decrease therapeutic effects. Capsaicin may increase the incidence of coughing. Diuretics (especially potassium-sparing diuretics) and potassium supplements may increase hyperkalemia associated with enalapril use. Increased adverse effects may occur when used with other renin-angiotensin system blockers or aliskiren.

Contraindications/Precautions: DO NOT USE DURING PREGNANCY. Use with caution in nursing mothers, in patients with impaired renal function, in patients undergoing surgery, or during anesthesia. Potentially fatal angioedema of the face, neck, and extremities has occurred during therapy. Pregnancy Category D.

Adverse Effects: Headache, dizziness, fatigue, diarrhea, rash, hypotension, cough, nausea, and orthostatic effects. A potentially severe adverse effect is angioedema.

Patient Consultation:

May be take without regard to meals.

Stop use and contact a physician if any signs of swelling occur.

Avoid nonprescription cough, cold, and allergy medications unless otherwise directed.

Avoid salt substitutes containing potassium.

Store in a cool, dry place away from sunlight and children.

If a dose is missed take it as soon as possible. If it is closer to the time of your next dose than the dose you missed, skip the missed dose and return to your dosing schedule. Do not double doses.

Contact a physician if the above side effects are severe or persistent.

Report any signs of neutropenia (fever, sore throat) to a physician.