Qbrelis

Drinking alcohol can further lower your blood pressure and may increase certain side effects of lisinopril.

Avoid becoming overheated or dehydrated during exercise, in hot weather, or by not drinking enough fluids. Lisinopril can decrease sweating and you may be more prone to heat stroke.

Do not use salt substitutes or potassium supplements while taking lisinopril, unless your doctor has told you to.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Lisinopril is used alone or together with other medicines to treat high blood pressure (hypertension). High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys resulting in a stroke, heart failure, or kidney failure. Lowering blood pressure can reduce the risk of strokes and heart attacks.

Lisinopril works by blocking a substance in the body that causes the blood vessels to tighten. As a result, lisinopril relaxes the blood vessels. This lowers blood pressure and increases the supply of blood and oxygen to the heart.

Lisinopril is also used to help treat heart failure. It is also used in some patients after a heart attack. After a heart attack, some of the heart muscle is damaged and weakened. The heart muscle may continue to weaken as time goes by. This makes it more difficult for the heart to pump blood. Lisinopril may be started within 24 hours after a heart attack to increase survival rate.

This medicine is available only with your doctor's prescription.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Blurred vision
• cloudy urine
• confusion
• decrease in urine output or decrease in urine-concentrating ability
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• sweating
• unusual tiredness or weakness

• Abdominal or stomach pain
• body aches or pain
• chest pain
• chills
• common cold
• cough
• diarrhea
• difficulty breathing
• ear congestion
• fever
• headache
• loss of voice
• nasal congestion
• nausea
• runny nose
• sneezing
• sore throat
• vomiting

• Arm, back, or jaw pain
• chest discomfort, tightness, or heaviness
• fast or irregular heartbeat
• general feeling of discomfort or illness
• joint pain
• loss of appetite
• muscle aches and pains
• shivering
• trouble sleeping

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Decreased interest in sexual intercourse
• inability to have or keep an erection
• lack or loss of strength
• loss in sexual ability, desire, drive, or performance
• rash

• Acid or sour stomach
• belching
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• feeling of constant movement of self or surroundings
• heartburn
• indigestion
• muscle cramps
• sensation of spinning
• stomach discomfort or upset
• swelling

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine (Qbrelis) affects you.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
• Have your blood pressure checked often. Talk with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• If you are taking a salt substitute that has potassium, potassium-sparing diuretics, or potassium, talk with your doctor.
• If you are on a low-salt or salt-free diet, talk with your doctor.
• If you are taking lithium, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with this medicine.
• If you are taking this medicine (Qbrelis) and have high blood pressure, talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
• Talk with your doctor before you drink alcohol.
• Be careful in hot weather or while being active. Drink lots of fluids to stop fluid loss.
• Tell your doctor if you have too much sweat, fluid loss, throwing up, or loose stools. This may lead to low blood pressure.
• This medicine may not work as well in black patients. Talk with the doctor.
• A very bad reaction called angioedema has happened with this medicine. Sometimes, this has been deadly. The chance of angioedema may be higher in black patients. Talk with the doctor.
• Low white blood cell counts have happened with captopril, a drug like this one. This may lead to more chance of getting an infection. Most of the time, this has happened in people with kidney problems, mainly if they have certain other health problems. Call your doctor right away if you have signs of infection like fever, chills, or sore throat. Talk with your doctor.
• If you are 65 or older, use this medicine (Qbrelis) with care. You could have more side effects.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Do not freeze.
• Protect from heat.

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 [see Clinical Pharmacology (12.3)].

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 [see Use in Specific Populations (8.4) and Clinical Studies (14.1)].

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 [see Warnings and Precautions (5.4), and Drug Interactions (7.1)]. 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 [see Warnings and Precautions (5.4)] 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 [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

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 [see Dosage and Administration (2.2) and Warnings and Precautions (5.4)].

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 [see Warnings and Precautions (5.2)].

Neprilysin Inhibitor

Patients taking concomitant neprilysin inhibitors may be at increased risk for angioedema [see Warnings and Precautions (5.2)].

Pregnancy

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.

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

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 [see Dosage and Administration (2.1) and Clinical Studies (14.1)]. 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[see Dosage and Administration (2.1), Clinical Pharmacology (12.3), and Clinical Studies (14.1)].

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 [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)].

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.

Bottle Label

NDC 52652-3001-1

Qbrelis™
(lisinopril)

Oral Solution
1 mg/mL

READY TO USE

150 mL
Silvergate
Pharmaceuticals Inc.
Rx Only

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

© Silvergate 2016

Each 1 mL contains
1 mg of lisinopril

Usual Dose:
See prescribing information.

Store at room temperature
20° - 25°C (68° - 77°F)
Avoid freezing and excessive heat.
Keep container tightly closed.

KEEP THIS AND ALL
MEDICATIONS OUT OF THE
REACH OF CHILDREN

70033324

Lot:
Exp: