FIRAZYR

Agents for Acute Treatment of Hereditary Angioedema (HAE)

Hazardous Drugs Classification
NIOSH 2016 List: Group 3
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.

NOTE: Patients may self-administer icatibant upon recognition of acute hereditary angioedema (HAE) attack, after appropriate training under the guidance of a healthcare professional.
For subcutaneous injection only.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Icatibant should be clear and colorless.

Supplied as a prefilled 30 mg syringe (10 mg/mL).
Remove the prefilled syringe and 25-gauge needle from the carton. Attach the needle to the syringe hub; do not use a different needle. Do not remove needle cap until immediately before administration.
Choose a site on the abdomen roughly 2 to 4 inches (5 to 10 cm) below the umbilicus on either side. The injection site should be at least 2 inches (5 cm) from any scars. Do not choose an area that is bruised, swollen, or painful.
Disinfect injection site (abdominal area) and allow to dry.
Uncap the needle. Hold prefilled syringe between fingers and thumb.
Gently pinch the fold of disinfected skin. Hold the syringe at a 45 to 90 angle to the skin.
Bring syringe toward skin and quickly insert the needle into the skin fold. Push the plunger, administer over at least 30 seconds, and until no medication remains in the syringe.
Release skin and gently pull needle out. Dispose of the used syringe and needle in sharps disposal container immediately after use.
May repeat at intervals of at least 6 hours if response is inadequate or symptoms recur. Do not administer more than 90 mg (3 doses) in 24 hours.[45450]

elevated hepatic enzymes / Delayed / 4.0-4.0
erythema / Early / Incidence not known
hematoma / Early / Incidence not known
edema / Delayed / Incidence not known
antibody formation / Delayed / Incidence not known

injection site reaction / Rapid / 97.0-97.0
fever / Early / 4.0-4.0
dizziness / Early / 3.0-3.0
rash / Early / 1.0
urticaria / Rapid / Incidence not known
ecchymosis / Delayed / Incidence not known
pruritus / Rapid / Incidence not known
headache / Early / Incidence not known
nausea / Early / Incidence not known

FIRAZYR, SAJAZIR

Rx

A selective bradykinin B2 receptor antagonist
Used subcutaneously to treat acute attacks of hereditary angioedema
May be administered by the patient

30 mg subcutaneously once. If response is inadequate or symptoms recur, may repeat dose at intervals of at least 6 hours. Max: 90 mg/24 hours.[45450]

30 mg subcutaneously once.

†Indicates off-label use

No dosage adjustments are needed.

No dosage adjustments are needed.

Amlodipine; Benazepril: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Angiotensin-converting enzyme inhibitors: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Benazepril: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Benazepril; Hydrochlorothiazide, HCTZ: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Captopril: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Captopril; Hydrochlorothiazide, HCTZ: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Enalapril, Enalaprilat: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Enalapril; Hydrochlorothiazide, HCTZ: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Fosinopril: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Fosinopril; Hydrochlorothiazide, HCTZ: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Hydrochlorothiazide, HCTZ; Moexipril: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Lisinopril: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Lisinopril; Hydrochlorothiazide, HCTZ: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Moexipril: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Perindopril: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Perindopril; Amlodipine: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Quinapril: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Quinapril; Hydrochlorothiazide, HCTZ: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Ramipril: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Trandolapril: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.
Trandolapril; Verapamil: (Minor) Although clinical data are lacking, icatibant is a bradykinin B2 receptor antagonist and may theoretically potentiate the antihypertensive effect of ACE inhibitors.

FIRAZYR/Icatibant/Icatibant acetate Subcutaneous Inj Sol: 1mL, 10mg

30 mg/dose subcutaneously. May repeat at intervals of 6 hours; no more than 90 mg/24 hours subcutaneously.

30 mg/dose subcutaneously. May repeat at intervals of 6 hours; no more than 90 mg/24 hours subcutaneously.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Icatibant is a competitive inhibitor of the bradykinin B2 receptor. Hereditary angioedema (HAE) is caused by a deficiency of C1 esterase inhibitor. A deficiency of C1 esterase inhibitor may result in an increase in plasma bradykinin concentrations. The characteristic symptoms of HAE, localized swelling, inflammation, and pain, are thought to be caused by an excessive production of bradykinin. Icatibant inhibits bradykinin from binding to the B2 receptor, thus treating the symptoms of an acute HAE attack.

Icatibant is administered subcutaneously. Vd at steady state is 29 +/- 8.7 L. Icatibant is extensively metabolized by proteolytic enzymes to inactive metabolites that are primarily excreted in the urine. Less than 10% of the dose is eliminated as unchanged drug. Plasma clearance is 245 +/- 58 mL/minute, and mean half-life is 1.4 +/- 0.4 hours.
 
Intravenous icatibant (0.4 and 0.8 mg/kg over 4 hours) caused dose and time-dependent inhibition in the development of bradykinin-induced vasodilation, hypotension, and reflex tachycardia in healthy young subjects for 6 to 8 hours. Based on exposure-response analysis, a subcutaneous dose of 30 mg is predicted to be effective against bradykinin challenge for at least 6 hours.
 
Affected cytochrome P450 isoenzymes and drug transporters: none

After a 30 mg subcutaneous dose, icatibant has an absolute bioavailability of 97%. The mean Cmax of 974 +/- 280 ng/mL is seen after 0.75 hours. The mean AUC is 2,165 +/- 568 ng x hour/mL, and there is no evidence of accumulation following three 30-mg doses administered 6 hours apart.

There are no data on the presence of icatibant in human milk, the effects on the breastfed infant, or the effects on milk production. The manufacturer states that systemic absorption in infants following oral exposure of icatibant through breast milk is not expected. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.