Serious Warnings and Precautions In critically ill patients, including patients with sepsis, use of hydroxyethyl starch (HES) products, including VOLUVEN®, increase risk of mortality and renal replacement therapy. Do not use HES products, including VOLUVEN®, in critically ill patients, including patients with sepsis.
General:
Fluid overload caused by overdose should be avoided in general. Particularly, for patients with cardiac insufficiency or severe kidney dysfunctions the increased risk of hyperhydration must be taken into consideration; posology must be adapted.
Fluid status and rate of infusion should be assessed regularly during treatment, especially in patients with cardiac insufficiency or severe kidney dysfunction. In case of severe dehydration a crystalloid should be given first. Generally, sufficient fluid should be administered in order to avoid dehydration.
Particular care must be taken in patients with electrolyte abnormalities like hypernatremia and hyperchloremia. Clinical evaluation and periodic laboratory determinations are necessary to monitor fluid balance, serum electrolyte concentrations, kidney function, acid-base balance, and coagulation parameters during prolonged parenteral therapy or whenever the patient’s condition warrants such evaluation.
Carcinogenesis and Mutagenesis:
See PART II: SCIENTIFIC INFORMATION – Toxicology – Mutagenicity study.
Hematologic:
Monitor the coagulation status in patients undergoing open heart surgery in association with cardiopulmonary bypass as excess bleeding has been reported with other HES solutions in this population. Discontinue the use of VOLUVEN® at the first sign of clinically relevant coagulopathy.
Administration of large volumes of hydroxyethyl starch may transiently alter the coagulation mechanism and decrease hematocrit and plasma proteins due to hemodilution.
Hepatic/Biliary/Pancreatic:
Serum amylase can rise during administration of VOLUVEN® and can interfere with the diagnosis of pancreatitis. The elevated amylase is due to the formation of an enzyme-substrate complex of amylase and hydroxyethyl starch subject to slow elimination and must not be considered diagnostic of pancreatitis.
6) Page 5 of 24 Monitor liver function in patients receiving HES products, including VOLUVEN®.
Immune:
Anaphylactic/anaphylactoid reactions (hypersensitivity, mild influenza-like symptoms, bradycardia, tachycardia, bronchospasm, non-cardiac pulmonary edema) have been reported with solutions containing hydroxyethyl starch. If a hypersensitivity reaction occurs, administration of the drug should be discontinued immediately and the appropriate treatment and supportive measures should be undertaken until symptoms have resolved (please refer to section ADVERSE REACTIONS).
Renal:
Avoid use in patients with pre-existing renal dysfunction. Discontinue use of VOLUVEN® at the first sign of clinically relevant renal injury. Continue to monitor renal function in hospitalized patients for at least 90 days as use of renal replacement therapy has been recorded up to 90 days after administration of HES products.
Skin:
Pruritus is a known complication of administration of hydroxyethyl starches, though it is more common with prolonged use of high doses HES-induced pruritus may be delayed in onset, typically one to six weeks after exposure, may be severe and may be of protracted (weeks and months) persistence.
It is generally unresponsive to therapy.
Special populations Pregnant Women:
There are no adequate and well-controlled studies using VOLUVEN® in pregnant women. However, animal studies do not indicate harmful effects with respect to embryo/fetal development, pregnancy, parturition or postnatal development. There were no post-marketing reports of harm when VOLUVEN® was used in pregnant women.
9% sodium chloride solution is given at 50 mL/kg BW/day. No evidence of teratogenicity was observed. VOLUVEN® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Information on the use of VOLUVEN® during labour or delivery is unknown.
Use if clearly needed. 4 is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when VOLUVEN® is administered to a nursing mother. A decision on whether to continue/discontinue breast-feeding or to discontinue/continue therapy with VOLUVEN® should be made taking into account the benefit of breast-feeding to the child and the benefit of VOLUVEN® therapy to the nursing mother.
Pediatrics:
Data are limited in children, therefore it is not recommended to use HES products in this population.
Geriatrics:
Of the total number of patients in clinical trials of VOLUVEN® (N=471), 25% were 65-75 years old, while 7% were 75 and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.
Other reported experience has not identified specific risks for the application of VOLUVEN® in this patient group. ADVERSE REACTIONS Adverse reactions with VOLUVEN® reported spontaneously, from clinical trials and in the literature include: Immune system disorders Rare: Anaphylactic/anaphylactoid reactions (hypersensitivity, mild influenza-like symptoms, bradycardia, tachycardia, bronchospasm, non-cardiac pulmonary edema) have been reported with solutions containing hydroxyethyl starch (see WARNINGS AND PRECAUTIONS).
Abnormal Hematologic and Clinical Chemistry Findings (Investigations) Common (dose dependent): Increase in serum amylase (see WARNINGS AND PRECAUTIONS).
Common (dose dependent):
At high dosages the dilution effects may result in a corresponding dilution of blood components such as coagulation factors and other plasma proteins and in a decrease of hematocrit. Skin and subcutaneous tissue disorders […]