Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

PRINIVIL (NDA-019558)

(LISINOPRIL)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

Download Data

Expand all

11/09/2021 (SUPPL-63)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Fetal Toxicity

Additions underlined

PRINIVIL 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. 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 PRINIVIL as soon as possible [see Use in Specific Populations (8.1)].

8 Use in Specific Populations

8.1 Pregnancy

PLLR conversion

Risk Summary

PRINIVIL 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 PRINIVIL as soon as possible.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the

U.S. general 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 therapy to drugs affecting the

renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus.

In patients taking PRINIVIL during pregnancy, perform serial ultrasound examinations to assess the intra- amniotic environment. Fetal testing may be appropriate, based on the week of gestation. If oligohydramnios is observed, discontinue PRINIVIL, unless it is considered lifesaving for the mother.

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 PRINIVIL for hypotension, oliguria, and hyperkalemia. In neonates with a history of in utero exposure to PRINIVIL, if oliguria or hypotension occurs, support 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.

8.2 Lactation

PLLR conversion

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 many drugs are secreted in human milk, and because of the potential for serious adverse reactions in the breastfed infants from ACE inhibitors, discontinue breastfeeding or discontinue PRINIVIL.

10/12/2018 (SUPPL-62)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.5 Hyperkalemia

(addition underlined)

Monitor serum potassium periodically in patients receiving PRINIVIL. 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, potassium-containing salt substitutes, or other drugs that may increase serum potassium.

7 Drug Interactions

7.1 Diuretics

(addition underlined)

…

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

09/19/2017 (SUPPL-61)

Approved Drug Label (PDF)

4 Contraindications

(additions underlined)

PRINIVIL 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 coadminister aliskiren with PRINIVIL in patients with diabetes. PRINIVIL is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer PRINIVIL within 36 hours of switching to or from sacubitril/valsartan, a product containing a neprilysin inhibitor.

5 Warnings and Precautions

5.2 Angioedema and Anaphylactoid Reactions

(additions underlined)

…

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

Patients receiving concomitant ACE inhibitor and neprilysin inhibitor therapy may be at increased risk for angioedema.

7 Drug Interactions

7.8 Neprilysin Inhibitors

(new subsection added)

Patients taking a concomitant neprilysin inhibitor (e.g., sacubitril) may be at increased risk for angioedema.