6. ADVERSE REACTIONS

 

6.1. Clinical Trials Experience

 

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

 

ATHOS-3 

 

The safety of GIAPREZA was eva luated in ATHOS-3 [see Warnings and Precautions(5.1)]. Patients in ATHOS-3 were receiving other vasopressors in addition to GIAPREZA or placebo, which were titrated to effect on mean arterial pressure (MAP).

 

Table 2 summarizes adverse reactions with an incidence of at least 4% among patients treated with GIAPREZA and with a rate of at least 1.5% higher with GIAPREZA than with placebo.

 

Table 2: Adverse Reactions Occurring in ≥ 4% of Patients Treated with GIAPREZA and ≥ 1.5% More Often than in Placebo-treated Patients in ATHOS-3 

Adverse Event

 

GIAPREZA

N=163

 

Placebo

N=158

* Including arterial and venous thrombotic events  

 

Thromboembolic events* 21 (12.9%) 8 (5.1%) 

  Deep vein thrombosis 7 (4.3%) 0 (0.0%) 

Thrombocytopenia 16 (9.8%) 11 (7.0%) 

Tachycardia 14 (8.6%) 9 (5.7%) 

Fungal infection 10 (6.1%) 2 (1.3%) 

Delirium 9 (5.5%) 1 (0.6%) 

Acidosis 9 (5.5%) 1 (0.6%) 

Hyperglycemia 7 (4.3%) 4 (2.5%) 

Peripheral ischemia 7 (4.3%) 4 (2.5%) 

7. DRUG INTERACTIONS

 

7.1. Angiotensin Converting Enzyme (ACE) Inhibitors

 

Concomitant use of angiotensin converting enzyme (ACE) inhibitors may increase the response to GIAPREZA.

 

7.2. Angiotensin II Receptor Blockers (ARB)

 

Concomitant use of angiotensin II blockers (ARBs) may decrease the response to GIAPREZA.

 

8. USE IN SPECIFIC POPULATIONS

8.1. Pregnancy

 

Risk Summary 

 

The published data on angiotensin II use in pregnant women are not sufficient to determine a drug-associated risk of adverse developmental outcomes. Animal reproduction studies have not been conducted with GIAPREZA.

 

All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

 

Clinical Considerations 

 

Disease-associated maternal and/or embryo/fetal risk 

 

Septic or other distributive shock is a medical emergency that can be fatal if left untreated. Delaying treatment in pregnant women with hypotension associated with septic or other distributive shock is likely to increase the risk of maternal and fetal morbidity and mortality.

8.2. Lactation

 

Risk Summary 

 

It is not known whether GIAPREZA is present in human milk. No data are available on the effects of angiotensin II on the breastfed child or the effects on milk production.

 

8.4. Pediatric Use