Drug
Mechanism
Dose
Danazol
(Danocrine)
Antigonadotropic agent;
increases production of
C1INH.
Adult:

50, 100, 200 mg
capsules


ε-aminocaproic
acid (Amicar)
500, 1000 mg
tablets
0.25 g/mL oral
solution
Tranexamic acid
(Cyklokapron,
Lysteda)
500, 650 mg tablets
Lysine analog that
inhibits fibrinolysis via
inhibition of plasminogen
activator substances and
antiplasmin activity.
Half-life is 1-2 hours.
Peak effect occurs within
2 hours.
Inhibits fibrinolysis by
displacing plasminogen
from fibrin.
Adult:


Approximate
Cost
Short-term prophylaxis for minor
procedure: 2.5-10 mg/Kg/d,
maximum 600 mg/d for 5 days
prior and 2-5 days after event
30 x 50 mg: $53
30 x 100 mg: $69
30 x 200 mg: $111
Long term prophylaxis: ≤200
mg/day, use lowest effective
dose (including alternate day or
2-3 times/week regimens)

Caution with carbamazepime and warfarin. Caution in renal, hepatic, or cardiac
insufficiency and seizure disorders; hepatitis and benign hepatic adenoma have
been observed with long-term therapy (>10 y); thromboembolic events and
pseudotumor cerebri reported; androgenlike effects, including weight gain, acne,
hirsutism, edema, hair loss, voice changes, and menstrual disturbances, occur.

Monitoring: LFTs, lipid profile, CBC, and UA q6 months. For adults with a dose of
≤200 mg/d: annual liver/spleen ultrasound. In prepubertal patients or adults with
doses >200 mg/d: liver/spleen ultrasound q6 months and annual α-fetoprotein.

Pregnancy category X. Androgen contraindications also include lactation,
cancer, hepatitis, and childhood (until puberty finished). Short term prophylaxis
may be used during third trimester of pregnancy or in children if C1INH
replacement not available.

Caution in cardiac, hepatic, or renal disease; adverse effects are postural
hypotension, thrombosis, and muscular pain and weakness due to risk of
rhabdomyolysis; caution in patients with upper urinary tract bleeding; caution
with rapid infusions; do not administer with factor IX complex concentrates or
anti-inhibitor coagulant complexes.

Antifibrinolytics have not been associated with excess thrombosis or myocardial
infarction in controlled trials but there are case reports of thrombosis in patients
with hypercoagulable states so it is prudent to use them cautiously if there is a
family history of thrombophilia or active thromboembolic disease.

Monitor CK and aldolase levels, UA, LFT, and renal function q6 months.

Antifibrinolytics may not be as effective as androgen therapy in HAE but may be
useful in acquired angioedema.

Pregnancy category C.

Caution in renal impairment; adverse effects are not common but include
headaches, nausea, abdominal pain, and diarrhea; risk of rhabdomyolysis but
less than in aminocaproic acid; evidence of tumor formation in retina and liver
found in experimental animal models after long-term use; although no evidence
has supported these findings in humans.

Antifibrinolytics have not been associated with excess thrombosis or myocardial
infarction in controlled trials but there are case reports of thrombosis in patients
with hypercoagulable states so it is prudent to use them cautiously if there is a
family history of thrombophilia or active thromboembolic disease.

Monitoring: CK, UA, LFT and renal function q6 months; annual ophthalmology
check for eye pressure, baseline ophthalmology exam before long term use.

Antifibrinolytics may not be as effective as androgen therapy in HAE but may be
useful in acquired angioedema.

Mostly used for prophylaxis in children before Tanner 5 puberty or if not wanting
to risk androgen prophylaxis

Pregnancy category B.
Acute attack: some patients on
androgens can abort attacks by
doubling their prophylaxis dose
at the first signs or prodrome of
an attack.
30 x 500 mg: $103
Acute attack: 8 g q4h IV, then 16
g/d
Maintenance: 6-10 g/d PO
Pediatric:

8-10 g/d PO

Not recommended in newborns
Adult:


Notes
60 x 500 mg: $70
Acute attack: Up to 8 g PO/IV
Long term prophylaxis: 20-50
mg/Kg/d div. bid or tid, maximum
3-6 g/day
Pediatric:

12-25 mg/Kg/dose (not to
exceed 1.5 g) PO tid/qid
Fresh frozen
plasma (FFP)
Replacement of deficient
or dysfunctional
endogenous C1INH.
1 unit (~400 mL)
Blood product: after a
unit of blood is drawn,
cell components
(WBC/RBC/ platelets)
removed by
centrifugation and
remaining portion is
frozen.
Nanofiltered
human C1INH
(Cinryze)
Replacement of deficient
or dysfunctional
endogenous C1INH.
Adolescent/adult:

Acute attack: 1-2 units (400-800
mL) IV

Short term prophylaxis for major
procedure: 1-2 units (400-800
mL) IV 1-6 hours before
procedure + danazol short term
prophylaxis
Adolescent/adult:

Abdominal or facial attacks: 20
U/Kg IV, infusion rate ≤4 mL/min

Human C1INH
(Berinert)
Replacement of deficient
or dysfunctional
endogenous C1INH.
500 unit vial
Anecdotal reports of worsening angioedema. Universal precautions for bloodborne infection.

Severe hypersensitivity may occur and result in urticaria, chest tightness,
wheezing, hypotension, and/or anaphylaxis; thrombotic events have been
reported with high doses .20 U/Kg; as with all products derived from human
blood, universal precautions for infection transmission should be used; common
adverse effects (ie, >5%) include URTIs, sinusitis, rash, and headache.

Pregnancy category C.

Made from human plasma and may contain infectious agents, eg, viruses and,
theoretically, Creutzfeldt-Jakob disease (CJD). Hyper-sensitivity reactions may
occur and result in urticaria, chest tightness, wheezing, hypotension, and/or
anaphylaxis; thrombotic events have occurred with high doses >20 U/Kg;
common adverse effects (>4%) include nausea, vomiting, diarrhea, dysgeusia,
abdominal pain, muscle spasms, and headache; may increase severity of pain
associated with HAE.

Pregnancy category C. It is not known whether Berinert is excreted in human
milk.

Likely to be similar to plasma-derived C1INH except there is no risk of human
blood-borne infection.
Pediatric:

Acute attack or short term
prophylaxis: 10 mL/Kg

500 unit vial

Short term prophylaxis for major
procedure: 10-20 U/Kg IV 1-6
hours before procedure
500 unit vial: $2340
70 Kg patient:
$9360 (4 vials) for
acute treatment,
$243,360 per year
for biweekly
prophylaxis.
Long term prophylaxis: 1000 U
IV over 10 min q3-4 days
Adolescent/adult ≥13 years old acute
attack:

20 U/Kg IV, infusion rate ≤4
mL/min
500 unit vial: $850
70 Kg patient =
$3400 (4 vials)
Half-life 18.4 ± 3.5 hours
Recombinant
human C1INH
(Ruconest, Rhucin)
Replacement of deficient
or dysfunctional
endogenous C1INH.
Secreted in transgenic
rabbit’s milk; identical
amino acid sequence to
endogenous human
C1INH
Adult: 50-100 U/Kg reported in literature
N/A
Icatibant (Firazyr)
30 mg (3 mL)
syringe
Ecallantide
(Kalbitor)
3 x 10 mg (1 mL)
syringes
Bradykinin B2 receptor
antagonist
Following subcutaneous
administration, the
absolute bioavailability is
97%. The time to
maximum concentration
is ~0.5 hours. The halflife is 1-2 hours. Mainly
eliminated by liver
metabolism with less
than 10% of the dose
eliminated in the urine as
unchanged drug.
Plasma kallikrein
inhibitor. Ecallantide
binds to plasma kallikrein
and blocks its binding
site, inhibiting the
conversion of HMW
kininogen to bradykinin.
Produced by yeast (P.
pastoris).
Maximum plasma
concentration was
observed approximately
2-3 hours post-dose.
Ecallantide is a small
protein and renal
elimination has been
demonstrated.
Adult acute attack:

30 mg SQ

In case of insufficient relief or
recurrence of symptoms, a
second dose can be given after 6
hours, if the second dose
produces insufficient relief or if
symptoms recur, a third doe can
be given after a further 6 hours.
No more than 3 injections should
be given in a 24 hour period.
Adolescent/adult ≥16 years old acute
attack:

30 mg given as three 10 mg SQ
injections.

If attack persists, additional 30
mg may be given within a 24
hour period (at least 4 hours
after initial dose).

The site for each injection may
be in the same or different
locations (abdomen, thigh, upper
arm). Sites should be separated
by 5 cm and away from the
anatomical site of attack.
Pediatric acute attack (off-label):

10-20 mg given as 1-2 10 mg SQ
injections
N/A
30 mg: $7950

Special precautions: In ischemic heart disease, a deterioration of cardiac
function and a decrease in coronary blood flow could theoretically arise from
antagonism of bradykinin B2 receptor. Caution when administering to patients
with acute ischemic heart disease or unstable angina pectoris. In addition,
caution should be observed in the administration of icatibant to patients in the
weeks following a stroke. Although there is evidence to support a beneficial
effect of B2 receptor blockade immediately following a stroke, there is a
theoretical possibility that icatibant may attenuate the positive late phase
neuroprotective effects of bradykinin.

Most common adverse reaction is self-limited erythema, swelling, warm
sensation, burning, itching, and cutaneous pain at the injection site.

Icatibant should be used during pregnancy only if the potential benefit justifies
the potential risk to the fetus, (e.g for treatment of potentially life threatening
laryngeal attacks). It is unknown whether icatibant is excreted in human breast
milk but it is recommended that breastfeeding women should not breastfeed for
12 hours after treatment.

FDA blackbox warning for anaphylaxis: occurred in 3.9% of treated patients.
Given the similarity in hypersensitivity symptoms and acute HAE, monitor
patients closely for hypersensitivity reactions.

Patients may develop antibodies to ecallantide. Rates of seroconversion
increase with exposure In the Kalbitor HAE program, 7.4% of patients
seroconverted to anti-ecallantide antibodies. Neutralizing antibodies to
ecallantide were determined in vitro to be present in 4.7% of patients. Antiecallantide and anti-P. pastoris IgE antibodies were also detected. Patients who
seroconvert may be at a higher risk of a hypersensitivity reaction. The long-term
effects of antibodies to ecallantide are not known.

The most common adverse reactions occurring in ≥3% of treated patients and
greater than placebo are headache, nausea, diarrhea, pyrexia, injection site
reactions, and nasopharyngitis.

Pregnancy category C.