• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Safety

  • Print
  • Share
  • E-mail

Altace (ramipril) capsules

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

 

May 2014

Summary View

5 WARNINGS AND PRECAUTIONS

5.7 Dual Blockade of the Renin-Angiotensin Aldosterone System
  • added...Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors.

7 DRUG INTERACTIONS

7.2 Other Agents Affecting RAS
  • In general, avoid combined use of RAS inhibitors. [see Warnings and Precautions (5.7)]. Do not co-administer aliskiren with ALTACE in patients with diabetes [see Contraindications (4)]. 

  

October 2013

Summary View

CONTRAINDICATIONS

  • Do not co-administer aliskiren with Altace in patients with diabetes.

WARNINGS AND PRECAUTIONS

Dual Blockade of the Renin-Angiotensin- Aldosterone System

  • Avoid concomitant use of aliskiren with Altace

DRUG INTERACTIONS

Aliskiren
  • Avoid concomitant use of aliskiren with Altace

 

September 2013

Summary View

4 CONTRAINDICATIONS

  • Do not co-administer aliskiren with ALTACE in patients with diabetes or in patients with renal impairment (GFR < 60 mL/min/1.73 m2)

5 WARNINGS AND PRECAUTIONS

5.1 Anaphylactoid and Possibly Related Reactions
  • Patients taking concomitant mTOR inhibitor (e.g. temsirolimus) therapy may be at increased risk for angioedema. [see Drug Interactions (7.7)]
5.7 Dual Blockade of the Renin-Angiotensin-Aldosterone System
  • 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 blood pressure, renal function and electrolytes in patients on ALTACE and other agents that affect the RAS.

Aliskiren

  • Do not co-administer aliskiren with ALTACE in patients with diabetes or in patients with renal impairment (GFR <60 mL/min/1.73 m2). [see Drug Interactions (7.6)]

DRUG INTERACTIONS

7.6 Aliskiren
  • Do not co-administer aliskiren with ALTACE in patients with diabetes or in patients with renal impairment (GFR <60 mL/min/1.73 m2). [see Warnings and Precautions (5.7)].
7.7 mTOR Inhibitors
  • Patients taking concomitant mTOR inhibitor (e.g. temsirolimus) therapy may be at increased risk for angioedema. [see Warnings and Precautions (5.1)] 

 

April 2012

Summary View

BOXED WARNING

WARNING: FETAL TOXICITY
  • When pregnancy is detected, discontinue Altace as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus
 

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…
 

USE IN SPECIAL POPULATIONS

Pregnancy
  • 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…
 
Pediatric Use
  • Neonates with a history of in utero exposure to ALTACE: If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion…
 

PATIENT COUNSELING INFORMATION

Pregnancy
  • Female patients of childbearing age should be told about the consequences of exposure to Altace during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible...

 

October 2010

Summary View

 

BOXED WARNING

WARNING: AVOID USE IN PREGNANCY
  • When used in pregnancy, ACE inhibitors can cause injury and death to the developing fetus. When pregnancy is detected, discontinue Altace as soon as possible.

 

WARNINGS AND PRECAUTIONS

Hepatic Failure and Impaired Liver Function
  • ...Discontinue Altace if patient develops jaundice or marked elevations of hepatic enzymes.
Hypotension
  • Heart Failure Post-Myocardial Infarction: If the initial dose of 2.5 mg Altace cannot be tolerated, use an initial dose of 1.25 mg Altace to avoid excessive hypotension. Consider reducing the dose of concomitant diuretic to decrease the incidence of hypotension.
  • General Considerations: Correct volume- and salt-depletion before initiating therapy with Altace.
Dual Blockade of the Renin-Angiotensin-Aldosterone System
  • Telmisartan: The ONTARGET trial enrolled 25,620 patients >55 years old with atherosclerotic disease or diabetes with end-organ damage, randomized them to telmisartan only, ramipril only, or the combination, and followed them for a median of 56 months. Patients receiving the combination of telmisartan and ramipril did not obtain any benefit in the composite endpoint of cardiovascular death, MI, stroke and heart failure hospitalization compared to monotherapy, but experienced an increased incidence of clinically important renal dysfunction (death, doubling of serum creatinine, or dialysis) compared with groups receiving telmisartan alone or ramipril alone. Concomitant use of telmisartan and ramipril is not recommended.

 

DRUG INTERACTIONS

Other Antihypertensive Agents
  • In a large-scale, long-term clinical efficacy study, the combination of telmisartan and ramipril resulted in an increased incidence of clinically important renal dysfunction (death, doubling of serum creatinine, dialysis) compared with groups receiving either drug alone. Therefore, concomitant use of telmisartan and ramipril is not recommended.

 

USE IN SPECIFIC POPULATIONS

Pregnancy
  • Pregnancy Categories C (first trimester) and D (second and third trimesters).
Nursing Mothers
  • ...do not use Altace in nursing mothers.
Renal Impairment
  • A single-dose pharmacokinetic study was conducted in hypertensive patients with varying degrees of renal impairment who received a single 10 mg dose of ramipril. Patients were stratified into four groups based on initial estimates of creatinine clearance: normal (>80 mL/min), mild impairment (40-80 mL/min), moderate impairment (15-40 mL/min), and severe impairment (<15 mL/min). On average, the AUC0-24h for ramiprilat was approximately 1.7-fold higher, 3.0-fold higher, and 3.2-fold higher in the groups with mild, moderate, and severe renal impairment, respectively, compared to the group with normal renal function. Overall, the results suggest that the starting dose of ramipril should be adjusted downward in patients with moderate-to-severe renal impairment.