Included as part of the PRECAUTIONS section.
- Avoid use in patients with pre-existing renal dysfunction
- Discontinue use of HEXTEND at the first sign of renal
- Continue to monitor renal function in hospitalized
patients for at least 90 days as use of renal replacement therapy (RRT) has
been reported up to 90 days after administration of HES products
- Monitor the coagulation status of patients undergoing
open heart surgery in association with cardiopulmonary bypass as excess
bleeding has been reported with HES solutions in this population. Discontinue
use of HEXTEND at the first sign of coagulopathy
- Monitor liver function in patients receiving HES
products, including HEXTEND
Solutions containing calcium should not be administered
simultaneously with blood through the same administration set because of the
likelihood of coagulation.
Life threatening anaphylactic/anaphylactoid reactions
have been rarely reported with solutions containing hetastarch; death has
occurred, but a causal relationship has not been established. Patients who develop
severe anaphylactic/anaphylactoid reactions may need continued supportive care
until symptoms have resolved.
Hypersensitivity reactions can occur even after solutions
containing hetastarch have been discontinued.
Solutions which contain potassium should be used with
great care, if at all, in patients with hyperkalemia and severe renal failure
and in situations in which potassium retention is present.
Solutions containing sodium ions should be used with
great care, if at all, in patients with congestive heart failure and severe
renal insufficiency and in clinical states in which edema with sodium retention
In patients with diminished renal function,
administration of solutions containing sodium or potassium ions may result in
sodium or potassium retention.
Solutions containing lactate ions should be used with
great care in patients with metabolic or respiratory alkalosis. The
administration of lactate ions should be performed with great care when dealing
with conditions in which an increased level or an impaired utilization of these
ions occurs, such as severe hepatic insufficiency.
DO NOT USE IN LEUKAPHERESIS.
Usage In Plasma Volume Expansion
Large volumes of isotonic solutions containing 6% hetastarch
(HEXTEND or 6% Hetastarch in 0.9% Sodium Chloride Injection) may transiently
alter the coagulation mechanism due to hemodilution and a direct inhibitory
action on Factor VIII. Hemodilution by isotonic solutions containing 6%
hetastarch may also result in a 24 hour decline of total protein, albumin, and
fibrinogen levels and in transient prolongation of prothrombin, activated
partial thromboplastin, clotting, and bleeding times.
Increased bleeding has been reported in patients
undergoing open heart surgery in association with cardiopulmonary bypass
following the use of 6% Hetastarch in 0.9% Sodium Chloride Injection.5,6
Although the electrolyte content of HEXTEND resembles that of the principal
ionic constituents of normal plasma, its 6% Hetastarch component is identical
to that of 6% Hetastarch in 0.9% Sodium Chloride Injection and has a direct
inhibitory action on Factor VIII. There are no retrospective studies similar to
those with 6% Hetastarch in 0.9% Sodium Chloride Injection that compare HEXTEND
to albumin in cardiopulmonary bypass surgery nor have any adequate and
well-controlled clinical studies been performed.
Hematocrit may be decreased and plasma proteins diluted
excessively by administration of large volumes of isotonic solutions containing
6% hetastarch. Administration of packed red cells, platelets, and fresh frozen
plasma should be considered if excessive dilution occurs.
In randomized, controlled, comparative studies of 6%
Hetastarch in 0.9% Sodium Chloride Injection (n = 92) and Albumin (n = 85) in
surgical patients, no patient in either treatment group had a bleeding complication
and no significant difference was found in the amount of blood loss between the
HEXTEND has not been adequately evaluated to establish
its safety in situations other than treatment of hypovolemia in elective
surgery. In some cases, the use of isotonic solutions containing 6% hetastarch has
been associated with coagulation abnormalities in conjunction with an acquired,
reversible von Willebrand's-like syndrome and/or Factor VIII deficiency when
used over a period of days. Replacement therapy should be considered if a
severe Factor VIII or von Willebrand deficiency is identified. If a coagulopathy
develops, it may take several days to resolve. Certain conditions may affect
the safe use of isotonic solutions containing 6% hetastarch on a chronic basis.
For example, in patients with subarachnoid hemorrhage where an isotonic
solution containing 6% hetastarch is used repeatedly over a period of days for
the prevention of cerebral vasospasm, significant clinical bleeding may occur. Intracranial
bleeding resulting in death has been reported with the use of 6% Hetastarch in
0.9% Sodium Chloride Injection.7
The possibility of circulatory overload should be kept in
mind. Caution should be used when the risk of pulmonary edema and/or congestive
heart failure is increased. Special care should be exercised in patients who
have impaired renal clearance since this is the principal way in which
hetastarch is eliminated and in clinical states in which edema with sodium
Indirect bilirubin levels of 8.3 mg/L (normal 0.0-7.0
mg/L) have been reported in 2 out of 20 normal subjects who received multiple
infusions of 6% Hetastarch in 0.9% Sodium Chloride Injection. Total bilirubin
was within normal limits at all times; indirect bilirubin returned to normal by
96 hours following the final infusion. The significance, if any, of these
elevations is not known; however, caution should be observed before
administering isotonic solutions containing 6% hetastarch to patients with a
history of liver disease.
If a hypersensitivity effect occurs, administration of
the drug should be discontinued and appropriate treatment and supportive
measures should be undertaken (seeWARNINGS AND PRECAUTIONS).
Caution should be used when administering solutions
containing hetastarch to patients allergic to corn because such patients can
also be allergic to hetastarch.
HEXTEND should be used with caution in patients who have
been anticoagulated with other drugs that negatively influence the coagulation
Clinical evaluation and periodic laboratory
determinations are necessary to monitor changes in fluid balance, electrolyte
concentrations, acid-base balance, and coagulation parameters during prolonged parenteral
therapy or whenever the condition of the patient warrants such evaluation.
Solutions containing dextrose should be used with caution
in patients with known subclinical or overt diabetes mellitus.
Caution must be exercised in the administration of
parenteral fluids, especially those containing sodium ions, to patients
receiving corticosteroids or corticotropin.
Potassium containing solutions should be used with
caution in the presence of cardiac disease, particularly in digitalized
patients or in the presence of renal disease.
Solutions containing lactate ions should be used with
caution as excess administration may result in metabolic alkalosis.
Elevated serum amylase levels may be observed temporarily
following administration of solutions containing hetastarch although no
association with pancreatitis has been demonstrated. Serum amylase levels
cannot be used to assess or to evaluate for pancreatitis for 3-5 days after
administration of solutions containing hetastarch. Elevated serum amylase
levels persist for longer periods of time in patients with renal impairment.
Solutions containing hetastarch have not been shown to increase serum lipase.
One report suggests that in the presence of renal
glomerular damage, larger molecules of hetastarch can leak into the urine and
elevate the specific gravity. The elevation of specific gravity can obscure the
diagnosis of renal failure.
Hetastarch is not eliminated by hemodialysis. The utility
of other extracorporeal elimination techniques has not been evaluated.
If administration is by pressure infusion, all air should
be withdrawn or expelled from the bag through the medication port prior to
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term studies of animals have not been performed to
evaluate the carcinogenic potential of hetastarch.
Pregnancy Category C
6% Hetastarch in 0.9% Sodium Chloride Injection has been
shown to have an embryocidal effect on New Zealand rabbits when given
intravenously over the entire organogenesis period in a daily dose ½ times the
maximum recommended therapeutic human dose (1500 mL) and on BD rats when given intraperitoneally,
from the 16th to the 21st day of pregnancy, in a daily dose 2.3 times the
maximum recommended therapeutic human dose. When 6% Hetastarch in 0.9% Sodium
Chloride Injection was administered to New Zealand rabbits, BD rats, and Swiss
mice with intravenous daily doses of 2 times, 1/3 times, and 1 times the
maximum recommended therapeutic human dose, respectively, over several days
during the period of gestation, no evidence of teratogenicity was evident.
There are no adequate and well controlled studies in pregnant women. HEXTEND
should be used during pregnancy only if the potential benefit justifies the
potential risk to the fetus.
It is not known whether hetastarch is excreted in human
milk. Because many drugs are excreted in human milk, caution should be
exercised when HEXTEND is administered to a nursing woman.
The safety and effectiveness of HEXTEND in pediatric
patients have not been established. Adequate, well-controlled clinical trials
to establish the safety and effectiveness of HEXTEND in pediatric patients have
not been conducted. However, in one small double-blind study, 47 infants,
children, and adolescents (ages 1 year to 15.5 years) scheduled for repair of
congenital heart disease with moderate hypothermia were randomized to receive
either 6% Hetastarch in 0.9% Sodium Chloride Injection or Albumin as a postoperative
volume expander during the first 24 hours after surgery. Thirty-eight children
required colloid replacement therapy, of which 20 children received 6%
Hetastarch in 0.9% Sodium Chloride Injection. No differences were found in the
coagulation parameters or in the amount of replacement fluids required in the
children receiving 20 mL/kg or less of either colloid replacement therapy. In
children who received greater than 20 mL/kg of 6% Hetastarch in 0.9% Sodium
Chloride Injection, an increase in prothrombin time was demonstrated (p =
0.006).8 There were no neonates included in this study.
Of the total number of patients in clinical trials of
HEXTEND (n=119), 30% were 65 or older while 12% were 70 or older. Other
reported experience with 6% Hetastarch in 0.9% Sodium Chloride Injection has not
identified differences in responses between elderly and younger patients, but
greater sensitivity of some older individuals cannot be ruled out.
This drug is known to be substantially excreted by the
kidney, and the risk of toxic reactions to this drug may be greater in patients
with impaired renal function. Because elderly patients are more likely to have
decreased renal function, care should be taken in dose selection, and it may be
useful to monitor renal function.
1. Diehl J, et al., Clinical Comparison of Hetastarch and
Albumin in Postoperative Cardiac Patients. The Annals of Thoracic Surgery,
2. Gold M, et al., Comparison of Hetastarch to Albumin
for Perioperative Bleeding in Patients Undergoing Abdominal Aortic Aneurysm
Surgery, Annals of Surgery, 1990;211(4):482-485.
3. Kirklin J, et al., Hydroxyethyl Starch versus Albumin
for Colloid Infusion Following Cardiopulmonary Bypass in Patients Undergoing
Myocardial Revascularization, The Annals of Thoracic Surgery, 1984;37(1):40-46.
4. Moggio RA, et al., Hemodynamic Comparison of Albumin
and Hydroxyethyl Starch in Postoperative Cardiac Surgery Patients, Critical
Care Medicine, 1983;11(12):943-945.
5. Knutson, JE, et al., Does Intraoperative Hetastarch
Administration Increase Blood Loss and Transfusion Requirements After Cardiac
Surgery? Anesthesia Analg., 2000;90: 801-7.
6. Cope, JT, et al., Intraoperative Hetastarch Infusion
Impairs Hemostasis After Cardiac Operations, The Annals of Thoracic Surgery,
7. Damon L, Intracranial Bleeding During Treatment with Hydroxyethyl
Starch, New England Journal of Medicine, 1987; 317(15):964-965.
8. Brutocao D, et al., Comparison of Hetastarch with
Albumin for Postoperative Volume Expansion in Children After Cardiopulmonary
Bypass, Journal of Cardiothoracic and Vascular Anesthesia, 1996;10(3):348-351.