IV bag icon
 

ZIIHERA is a single infusion every 2 weeks1

Premedications and Administration

  • Premedicate all patients 30 to 60 minutes prior to each dose of ZIIHERA to reduce the risk of infusion-related reactions1
    • Administer acetaminophen, an antihistamine and a corticosteroid1
  • Do not administer as an intravenous push or bolus1
  • Do not co-administer ZIIHERA and other intravenous drugs through the same intravenous line1
  • Administer ZIIHERA as an intravenous infusion with a 0.2 or 0.22 micron filter1
  • For full list of Preparation and Administration Instructions see Section 2 in the ZIIHERA full Prescribing Information

DOSAGE MODIFICATIONS FOR ADVERSE REACTIONS1

Left Ventricular Dysfunction (LVD)
 SeverityTreatment Modification
Left Ventricular Dysfunction (LVD)Absolute decrease of ≥16% points in LVEF from pre-treatment baseline 
or
LVEF ≤50% and absolute decrease of ≥10% points below pre-treatment baseline
  • Withhold ZIIHERA for at least 4 weeks
  • Repeat LVEF assessment within 4 weeks
  • Resume treatment within 4 to 8 weeks if LVEF returns to normal limits and the absolute decrease is ≤15% points from baseline
  • Permanently discontinue ZIIHERA if LVEF has not recovered to within 15% points from pre-treatment baseline
Confirmed symptomatic congestive heart failure
  • Permanently discontinue ZIIHERA
Infusion-Related Reactions (IRR)
 SeverityTreatment Modification
Infusion-Related Reactions (IRR)Mild 
(Grade 1)
  • Reduce infusion rate by 50%
  • For subsequent ZIIHERA infusions increase infusion rate gradually to the rate prior to the adverse reaction, as tolerated
Moderate 
(Grade 2)
  • Stop ZIIHERA infusion immediately
  • Treat with appropriate therapy
  • Resume ZIIHERA infusion at 50% of previous infusion rate once symptoms resolve
  • For subsequent ZIIHERA infusions increase infusion rate gradually to the rate prior to the adverse reaction, as tolerated
Severe 
(Grade 3)
  • Stop ZIIHERA infusion immediately
  • Promptly treat with appropriate therapy; infusion should not be restarted during the same cycle even if signs and symptoms completely resolve
  • Subsequent ZIIHERA infusions should be administered at 50% of previous infusion rate
  • Permanently discontinue ZIIHERA for recurrent Grade 3 reaction
Life threatening
(Grade 4)
  • Stop ZIIHERA infusion immediately and permanently discontinue
  • Promptly treat with appropriate therapy
Diarrhea
 SeverityTreatment Modification
DiarrheaMild/Moderate
(Grade 1 or 2)
  • No dosage modification of ZIIHERA is required
  • Initiate appropriate medical therapy and monitor as clinically indicated
Severe
(Grade 3)
  • Withhold ZIIHERA treatment until severity improves to Grade ≤1
  • Initiate or intensify appropriate medical therapy and monitor as clinically indicated
  • Administer subsequent ZIIHERA treatment at the same dose level or consider dose reduction to 15 mg/kg
  • For recurrent Grade 3 symptoms, withhold ZIIHERA treatment and ensure medical management has been optimized
    • Resume ZIIHERA treatment at a reduced dose of 15 mg/kg after severity improves to Grade ≤1
    • Permanently discontinue ZIIHERA for recurrent Grade 3 symptoms that last >3 days despite optimized medical management
Life threatening
(Grade 4)
  • Permanently discontinue ZIIHERA
Pneumonitis
 SeverityTreatment Modification
PneumonitisConfirmed Grade ≥2
  • Permanently discontinue ZIIHERA
Other Adverse Reactions (excluding LVD, IRR, Diarrhea, and Pneumonitis)
 SeverityTreatment Modification
Other Adverse Reactions (excluding LVD, IRR, Diarrhea, and Pneumonitis)Mild/Moderate 
(Grades 1 or 2)
  • No dose modification is required for ZIIHERA
  • Initiate appropriate medical therapy and monitor as clinically indicated
Severe 
(Grade 3)
  • Withhold ZIIHERA treatment until severity improves to Grade ≤1
  • Initiate appropriate medical therapy and monitor as clinically indicated
  • Administer subsequent ZIIHERA treatment at the same dose; consider dose reduction to 15 mg/kg if Grade 3 symptoms recur
Life threatening 
(Grade 4)
  • Permanently discontinue ZIIHERA, except as noted below
  • Initiate appropriate medical therapy and monitor as clinically indicated
  • ZIIHERA treatment may be resumed at the same dose level for Grade 4 electrolyte imbalances or laboratory abnormalities that are corrected within 3 days of onset; do not resume until symptoms improve to Grade ≤1
  • Permanently discontinue ZIIHERA for recurrent Grade 4 electrolyte imbalances, or laboratory abnormalities

LVEF=left ventricular ejection fraction.

 
Next:
Access

INDICATION

ZIIHERA (zanidatamab-hrii) 50 mg/mL for Injection for IV is indicated for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

IMPORTANT SAFETY INFORMATION AND INDICATION

WARNING: EMBRYO-FETAL TOXICITY
Exposure to ZIIHERA during pregnancy can cause embryo-fetal harm. Advise patients of the risk and need for effective contraception.

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity

ZIIHERA can cause fetal harm when administered to a pregnant woman. In literature reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death.

Verify the pregnancy status of females of reproductive potential prior to the initiation of ZIIHERA. Advise pregnant women and females of reproductive potential that exposure to ZIIHERA during pregnancy or within 4 months prior to conception can result in fetal harm. Advise females of reproductive potential to use effective contraception during treatment with ZIIHERA and for 4 months following the last dose of ZIIHERA.

Left Ventricular Dysfunction

ZIIHERA can cause decreases in left ventricular ejection fraction (LVEF). LVEF declined by >10% and decreased to <50% in 4.3% of 233 patients. Left ventricular dysfunction (LVD) leading to permanent discontinuation of ZIIHERA was reported in 0.9% of patients. The median time to first occurrence of LVD was 5.6 months (range: 1.6 to 18.7). LVD resolved in 70% of patients.

Assess LVEF prior to initiation of ZIIHERA and at regular intervals during treatment. Withhold dose or permanently discontinue ZIIHERA based on severity of adverse reactions.

The safety of ZIIHERA has not been established in patients with a baseline ejection fraction that is below 50%.

Infusion-Related Reactions

ZIIHERA can cause infusion-related reactions (IRRs). An IRR was reported in 31% of 233 patients treated with ZIIHERA as a single agent in clinical studies, including Grade 3 (0.4%), and Grade 2 (25%). IRRs leading to permanent discontinuation of ZIIHERA were reported in 0.4% of patients. IRRs occurred on the first day of dosing in 28% of patients; 97% of IRRs resolved within one day.

Prior to each dose of ZIIHERA, administer premedications to prevent potential IRRs. Monitor patients for signs and symptoms of IRR during ZIIHERA administration and as clinically indicated after completion of infusion. Have medications and emergency equipment to treat IRRs available for immediate use.

If an IRR occurs, slow, or stop the infusion, and administer appropriate medical management. Monitor patients until complete resolution of signs and symptoms before resuming. Permanently discontinue ZIIHERA in patients with recurrent severe or life-threatening IRRs.

Diarrhea

ZIIHERA can cause severe diarrhea.

Diarrhea was reported in 48% of 233 patients treated in clinical studies, including Grade 3 (6%) and Grade 2 (17%). If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Withhold or permanently discontinue ZIIHERA based on severity.

ADVERSE REACTIONS

Serious adverse reactions occurred in 53% of 80 patients with unresectable or metastatic HER2-positive BTC who received ZIIHERA. Serious adverse reactions in >2% of patients included biliary obstruction (15%), biliary tract infection (8%), sepsis (8%), pneumonia (5%), diarrhea (3.8%), gastric obstruction (3.8%), and fatigue (2.5%). A fatal adverse reaction of hepatic failure occurred in one patient who received ZIIHERA.

The most common adverse reactions in 80 patients with unresectable or metastatic HER2-positive BTC who received ZIIHERA (≥20%) were diarrhea (50%), infusion-related reaction (35%), abdominal pain (29%), and fatigue (24%).

USE IN SPECIFIC POPULATIONS

Pediatric Use

Safety and efficacy of ZIIHERA have not been established in pediatric patients.

Geriatric Use

Of the 80 patients who received ZIIHERA for unresectable or metastatic HER2-positive BTC, there were 39 (49%) patients 65 years of age and older. Thirty-seven (46%) were aged 65-74 years old and 2 (3%) were aged 75 years or older.

No overall differences in safety or efficacy were observed between these patients and younger adult patients.

Please click here to see the full Prescribing Information, including BOXED Warning.

Reference: 1. ZIIHERA (zanidatamab-hrii) Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc. 2024.