Included as part of the PRECAUTIONS section.
Emergency Patient Management
In addition to Cyanokit, treatment of cyanide poisoning must include immediate
attention to airway patency, adequacy of oxygenation and hydration, cardiovascular
support, and management of any seizure activity. Consideration should be given
to decontamination measures based on the route of exposure.
Use caution in the management of patients with known anaphylactic reactions
to hydroxocobalamin or cyanocobalamin. Consideration should be given to use
of alternative therapies, if available.
Allergic reactions may include: anaphylaxis, chest tightness, edema, urticaria,
pruritus, dyspnea, and rash.
Allergic reactions including angioneurotic edema have also been reported in
Blood Pressure Increase
Many patients with cyanide poisoning will be hypotensive; however, elevations
in blood pressure have also been observed in known or suspected cyanide poisoning
Elevations in blood pressure ( ≥ 180 mmHg systolic or ≥ 110 mmHg diastolic)
were observed in approximately 18% of healthy subjects (not exposed to cyanide)
receiving hydroxocobalamin 5 g and 28% of subjects receiving 10 g. Increases
in blood pressure were noted shortly after the infusions were started; the maximal
increase in blood pressure was observed toward the end of the infusion. These
elevations were generally transient and returned to baseline levels within 4
hours of dosing.
Use of Blood Cyanide Assay
While determination of blood cyanide concentration is not required for management
of cyanide poisoning and should not delay treatment with Cyanokit, collecting
a pretreatment blood sample may be useful for documenting cyanide poisoning
as sampling post-Cyanokit use may be inaccurate.
Interference with Clinical Laboratory Evaluations and Clinical Methods
Clinical Laboratory Evaluations
Because of its deep red color, hydroxocobalamin has been found to interfere
with colorimetric determination of certain laboratory parameters (e.g., clinical
chemistry, hematology, coagulation, and urine parameters). In-vitro tests indicated
that the extent and duration of the interference are dependent on numerous factors
such as the dose of hydroxocobalamin, analyte, methodology, analyzer, hydroxocobalamin
concentration, and partially on the time between sampling and measurement.
Based on in-vitro studies and pharmacokinetic data obtained in healthy volunteers,
the following table (Table 2) describes laboratory interference that may be
observed following a 5 g dose of hydroxocobalamin. Interference following a
10 g dose can be expected to last up to an additional 24 hours. The extent and
duration of interference in cyanide-poisoned patients may differ. Results may
vary substantially from one analyzer to another; therefore, caution should be
used when reporting and interpreting laboratory results.
Table 2 : Laboratory Interference Observed with In-Vitro
Samples of Hydroxocobalamin
||No Interference Observed
||Artificially Increased *
||Artificially Decreased *
||Duration of Interference
||24 hours with the exception of bilirubin (up to 4 days)
||12 - 16 hours
||aPTT PT (Quick or INR)
||24 - 48 hours
||pH (with all doses)
||pH (with equivalent doses of < 5 g)
||48 hoursup to 8 days; color changes may persist up to 28
|* ≥ 10% interference observed on at least
Analyzers used: ACL Futura (Instrumentation Laboratory),
AxSYM®/Architect™ (Abbott), BM Coasys110 (Boehringer Mannheim),
CellDyn 3700® (Abbott), Clinitek® 500 (Bayer), Cobas Integra®
700, 400 (Roche), Gen-S Coultronics, Hitachi 917, STA® Compact, Vitros®
950 (Ortho Diagnostics)
Because of its deep red color, hydroxocobalamin may cause hemodialysis machines
to shut down due to an erroneous detection of a “blood leak”. This
should be considered before hemodialysis is initiated in patients treated with
Hydroxocobalamin absorbs visible light in the UV spectrum. It therefore has
potential to cause photosensitivity. While it is not known if the skin redness
predisposes to photosensitivity, patients should be advised to avoid direct
sun while their skin remains discolored.
Patient Counseling Information
Cyanokit is indicated for cyanide poisoning and in this setting, patients will
likely be unresponsive or may have difficulty in comprehending counseling information.
Erythema and Chromaturia
Patients should be advised that skin redness may last up to 2 weeks and urine
coloration may last for up to 5 weeks after administration of Cyanokit. While
it is not known if the skin redness predisposes to photosensitivity, patients
should be advised to avoid direct sun while their skin remains discolored.
In some patients an acneiform rash may appear anywhere from 7 to 28 days following
hydroxocobalamin treatment. This rash will usually resolve without treatment
within a few weeks.
Pregnancy and Breast Feeding
Patients should be advised that maternal cyanide poisoning results in fetal
cyanide poisoning. Treatment for cyanide poisoning may be lifesaving for both
mother and fetus. Patients should notify their physician if they were pregnant
during therapy with Cyanokit [see Use In Specific Populations]. It is
not known whether hydroxocobalamin is excreted in human milk.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies have not been performed to evaluate the carcinogenic
potential of hydroxocobalamin. Hydroxocobalamin was negative in the following
mutagenicity assays: in vitro bacterial reverse mutation assay using
Salmonella typhimurium and Escherichia coli strains, an in-vitro assay of the
tk locus in mouse lymphoma cells, and an in-vivo rat micronucleus assay.
The effect of hydroxocobalamin on fertility has not been evaluated.
Use In Specific Populations
Pregnancy Category C
There are no adequate and well controlled studies of Cyanokit in pregnant women.
In animal studies, hydroxocobalamin caused skeletal and visceral (soft tissue)
abnormalities at exposures (based on AUC) similar to human exposures at the therapeutic dose. Cyanokit should be used during pregnancy only if the potential
benefit justifies the potential risk to the fetus. Because cyanide readily crosses
the placenta, maternal cyanide poisoning results in fetal cyanide poisoning.
Timely treatment of the pregnant mother may be lifesaving for both mother and
In animal studies, pregnant rats and rabbits received Cyanokit (75, 150, or
300 mg/kg/d) during the period of organogenesis. Following intraperitoneal dosing
in rats and intravenous dosing in rabbits, maternal exposures were equivalent
to 0.5, 1, or 2 times the human exposure at the therapeutic dose (based on AUC).
In the high dose groups for both species, maternal toxicity occurred, and there
was a reduced number of live fetuses due to embryofetal resorptions. In addition,
decreased live fetal weight occurred in high dose rats, but not in rabbits.
Incomplete skeletal ossification occurred in both rats and rabbits. In rats,
two fetuses of the high dose group and two fetuses of the mid dose group (each
from a different litter) had short, rudimentary or small front or hind legs.
Rabbit litters and fetuses exhibited a dose dependant increase in various gross
soft tissue and skeletal anomalies. The main findings in rabbits were flexed,
rigid flexor or medially rotated forelimbs or hindlimbs and domed heads at external
examination; enlarged anterior or posterior fontanelles of the ventricles of
the brain and flat, bowed or large ribs at skeletal examination; and dilated
ventricles of the brain, and thick wall of the stomach at visceral examination.
Labor and Delivery
The effect of Cyanokit on labor and delivery is unknown.
It is not known whether hydroxocobalamin is excreted in human milk. Cyanokit
may be administered in life-threatening situations, and therefore, breast-feeding
is not a contraindication to its use. Because of the unknown potential for adverse
reactions in nursing infants, the patient should discontinue nursing after receiving
Safety and effectiveness of Cyanokit have not been established in this population.
In non-US marketing experience, a dose of 70 mg/kg has been used to treat pediatric
Approximately 50 known or suspected cyanide poisoning victims aged 65 or older
received hydroxocobalamin in clinical studies. In general, the safety and effectiveness
of hydroxocobalamin in these patients was similar to that of younger patients.
No adjustment of dose is required in elderly patients.
The safety and effectiveness of Cyanokit have not been studied in patients
with renal impairment. Hydroxocobalamin and cyanocobalamin are eliminated unchanged
by the kidneys. Oxalate crystals have been observed in the urine of both healthy
subjects given hydroxocobalamin and patients treated with hydroxocobalamin following
suspected cyanide poisoning.
The safety and effectiveness of Cyanokit have not been studied in patients
with hepatic impairment.