Safety

Zestril (lisinopril) tablets

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)

April 2016

Summary View

USE IN SPECIFIC POPULATIONS

Pregnancy

Risk Summary

  • Zestril can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the reninangiotensin 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 reninangiotensin system from other antihypertensive agents. When pregnancy is detected, discontinue Zestril 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 Zestril for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occur in neonates with a history of in utero exposure to Zestril, 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 breast fed 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 Zestril.

 

September 2015

Summary View

WARNINGS AND PRECAUTIONS

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

DRUG INTERACTIONS

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

 

December 2014

Summary View

*The following was added:

DRUG INTERACTIONS

  • Dual blockade…RAS…  The VA NEPHRON trial enrolled 1448 patients with type 2 diabetes, elevated urinaryalbumin-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 state renal disease, or death, but experienced an increased incidence of hyperkalemia and acute kidney injury compared with the monotherapy group…

 

June 2014

Summary View

Content, Editorial and organizational changes were made throughout the label to comply with structured product labeling (SPL) formatIncluding content to the following safety sections

WARNINGS AND PRECAUTIONS
--Fetal Toxicity
Pregnancy Category D
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.

ADVERSE REACTIONS...

DRUG INTERACTIONS...

 

November 2013

Summary View

CONTRAINDICATIONS

  • Do not co-administer aliskiren with ZESTRIL in patients with diabetes

ADVERSE REACTIONS

Nervous System/Psychiatric
  • hallucinations

 

 

May 2009

Summary View

 

ADVERSE REACTIONS

Nervous System/Psychiatric

  • …and mood alterations (including depressive symptoms)

 

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