IMPORTANT SAFETY INFORMATION
QBRELIS® (lisinopril) Oral Solution, 1 mg/mL
WARNING: FETAL TOXICITY
See Full Prescribing Information for complete boxed warning.
- When pregnancy is detected, discontinue QBRELIS as soon as possible (5.1).
- Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus (5.1).
QBRELIS is an angiotensin-converting enzyme (ACE) inhibitor indicated for:
- Treatment of hypertension in adult patients and pediatric patients 6 years of age and older to lower blood pressure (BP). Lowering BP decreases the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions (MI).
- Reduction of signs and symptoms of systolic heart failure.
- Reduction of mortality in treatment of hemodynamically stable patients within 24 hours of acute MI. Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, aspirin, and beta-blockers.
Quality and Consistency of an FDA-Approved Oral Solution
The FDA reinforces the importance of prescribing an FDA-approved product such as Qbrelis.
According to the FDA:
“When a drug is FDA-approved, patients are assured that the FDA has reviewed the safety and efficacy of the drug and the adequacy of the manufacturing process to produce a quality product….compounded drugs do not provide such assurance and, therefore, should only be used when an FDA-approved product is not available to meet the medical needs of an individual patient.” *
* Hamburg MA. Department of Health and Human Services. Letter to: Colleague. January 8, 2014.
The FDA approval process helps ensure safety and effectiveness for your adult patients and patients age 6 years and older.
FDA-Approved Medications Differ From Extemporaneously Compounded Drugs
QBRELIS Oral Solution
|Compounded lisinopril suspension|
|Meets FDA standards for potency and purity*||Variable1,2|
|Required compliance with FDA’s CGMPs*||Variable2|
|Sourcing of active ingredient approved by FDA**||Variable1|
|Shelf life/stability*||Well established; Routinely monitored3||Variable1|
|Available at retail pharmacies||YES||Unknown|
|Covered by Medicaid||YES3||Unknown|
* Not all compounders are registered with the FDA; therefore, compounding is dependent on whether the product is compounded at a facility that meets the conditions of sections 503A of the FD&C Act or an outsourcing facility.
** In a 2004 published analysis sponsored by STD Pharmaceuticals, it was found that compounding samples purchased from three compounding pharmacies contained significant concentrations of a contaminant, suggesting a possible use of non-pharmaceutical grade chemicals.
1. Sellers S, Utian WH. Pharmacy Compounding Primer for Physicians. Drugs. 2012;72:2043-2050.
2. FDA/CDER. Guidance for Industry: Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and Cosmetic Act. January 2018.
3. Data on file, Azurity Pharmaceuticals, Inc.
4. Formulations: Lisinopril 1-mg/mL Oral Liquid. Int. J Pharm Comp. Vol 10. No. 4, July/August 2006:302.
Efficacy delivered with consistent potency when stored at controlled room temperature (20°C–25°C, 68°F–77°F) in a tightly closed container. Protect from freezing and excessive heat.
Well-established efficacy: The efficacy of lisinopril is well-established for the treatment of hypertension in adult patients and pediatric patients who are 6 years of age and older. Qbrelis is also indicated for adjunct therapy for heart failure and treatment of acute myocardial infarction.
Weight-based dosing: With Qbrelis (lisinopril) oral solution 1 mg/mL, you can provide weight-based dosing for the treatment of hypertension in children 6 years of age and older who have previously needed to rely on a manually prepared suspension.
Consistent potency: When you choose to prescribe or dispense Qbrelis, it provides consistent potency from first to last dose in every prescription, and helps ensure consistency from hospital to home.
ADDITIONAL IMPORTANT SAFETY INFORMATION:
QBRELIS is contraindicated in patients who are hypersensitive to lisinopril or any component of QBRELIS, or in patients with a history of hypersensitivity related to previous ACE inhibitor treatment.
QBRELIS is contraindicated in patients with hereditary or idiopathic angioedema.
Do not co-administer aliskiren with Qbrelis in patients with diabetes.
QBRELIS is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer QBRELIS within 36 hours of switching to or from sacubitril/valsartan.
Warnings and Precautions:
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 ACE inhibitors, including QBRELIS, at any time during treatment. 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 non-Black patients.
Intestinal angioedema has been reported with ACE inhibitors. Discontinue QBRELIS and obtain appropriate therapy.
Anaphylactoid Reactions: Sudden and potentially life-threatening anaphylactoid reactions have occurred in some patients dialyzed with high-flux membranes 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 and in patients undergoing desensitizing treatment with hymenoptera venom.
Impaired Renal Function: Monitor renal function in patients treated with QBRELIS. Changes in renal function, including acute renal failure, can be caused by drugs that inhibit the renin-angiotensin system (RAS). Patients whose renal function may depend in part on the activity of the RAS (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, post-MI 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. QBRELIS should be started under close medical supervision and followed closely for the first 2 weeks of treatment and whenever the dose of QBRELIS and/or a diuretic is increased. Avoid the use of QBRELIS in hemodynamically unstable patients after acute MI.
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 it is considered to be due to this mechanism, it can be corrected by volume expansion.
Hyperkalemia: Serum potassium should be monitored 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 and progresses to fulminant hepatic necrosis and sometimes death. If jaundice or marked elevations of hepatic enzymes develop, discontinue the ACE inhibitor and receive appropriate medical treatment.
See Full Prescribing Information for other Adverse Reactions (6).
Common adverse reactions where rate on lisinopril exceeds the rate on placebo by at least 2% by use are:
• Hypertension: headache, dizziness, and cough.
• Systolic heart failure: hypotension and chest pain.
• Acute MI: hypotension and renal dysfunction.
Initiation of QBRELIS in patients on diuretics may result in excessive reduction of blood pressure. This can be minimized by either decreasing or discontinuing the diuretic or increasing salt intake prior to initiating QBRELIS treatment.
QBRELIS attenuates potassium loss caused by thiazide-type diuretics. If concomitant use of such agents is indicated, monitor the patient’s serum potassium frequently.
Concomitant administration of QBRELIS and antidiabetic medicines may cause an increased blood-glucose-lowering effect.
In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, use of non-steroidal anti-inflammatory agents (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors, with ACE inhibitors, including lisinopril, may result in deterioration of renal function, including possible acute renal failure. Monitor renal function periodically in patients receiving lisinopril and NSAID therapy.
Dual Inhibition 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. Closely monitor BP, renal function and electrolytes in patients receiving QBRELIS and agents that effect the RAS.
Avoid use of aliskiren with QBRELIS in patients with renal impairment.
Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs that cause elimination of sodium, including ACE inhibitors. It is usually reversible upon discontinuation of lithium and the ACE inhibitor. Monitor serum lithium levels during concurrent use.
Nitritoid reactions have been reported rarely in patients with injectable gold (sodium aurothiomalate) and concomitant lisinopril therapy.
mTOR or neprilysin inhibitors: Patients receiving coadministration of an ACE inhibitor and a mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus) or a neprilysin inhibitor (e.g., sacubitril) may be at increased risk for angioedema.
Use in Specific Populations: See Full Prescribing Information for Additional Information (8).
QBRELIS can cause fetal harm. See Full Prescribing Information for Additional Information (5.1, 8.1).
Because of the potential for severe adverse reactions in the breastfed infant, advise women not to breastfeed while taking QBRELIS.
QBRELIS is not recommended in children under the age of 6 years or in pediatric patients with glomerular filtration rate < 30 mL/min/1.73m2.
This Important Safety Information does not include all the information needed to use QBRELIS safely and effectively. Visit QBRELIS.com for Full Prescribing Information
To report SUSPECTED ADVERSE REACTIONS, contact Azurity Pharmaceuticals, Inc. at 1-855-379-0383, or FDA at 1-800-FDA-1088 or www.fda.gov/MedWatch.