State Food and Drug Administration: Revised the instructions for hydroxyethyl starch injections

According to the results of the evaluation of adverse drug reactions, in order to further protect the safety of public medication, the State Drug Administration decided to treat hydroxyethyl starch injections (including hydroxyethyl starch sodium chloride injection, hydroxyethyl starch 40 sodium chloride injection, hypertonic sodium chloride hydroxyethyl starch 40 injection, hydroxyethyl starch 200/0.
5 sodium chloride injection, hypertonic hydroxyethyl starch 200/0.
5 sodium chloride injection, hydroxyethyl starch 130/0.
4 sodium chloride injection, hydroxyethyl starch 130/ 0.
4 sodium chloride injection, hydroxyethyl starch 130/ 0.
4 Electrolyte injection) instructions for unified revision
.
The relevant matters are hereby announced as follows: First, the holders of the marketing authorization of the above drugs shall report to the Drug Evaluation Center of the State Drug Administration or the provincial drug supervision and management department for the record before December 2, 2022 in accordance with the relevant provisions of the Measures for the Administration of Drug Registration and other relevant provisions, in accordance with the requirements for the revision of the instructions for
hydroxyethyl starch injections (see annex).
Where the revised content involves drug labels, they shall be revised together, and the instructions and other contents of the labels shall be consistent
with the original approved contents.
Drugs produced on the date of filing shall not continue to use the original drug instructions
.
The holder of the drug marketing authorization shall replace
the drug instructions and labels that have been shipped out of the factory within 9 months after filing.
Second, the holder of the drug marketing authorization shall carry out in-depth research on the mechanism of occurrence of new adverse reactions, take effective measures to do a good job in publicity and training on drug use and safety issues, and guide doctors and pharmacists to use drugs
rationally.
Clinicians and pharmacists should carefully read the revised contents of the above drug instructions, and when choosing drugs, they should conduct a full benefit/risk analysis according to the newly revised instructions
.
Fourth, patients should carefully read the drug instructions before taking the drug, and if they use prescription drugs, they should strictly follow the doctor's instructions
.
V.
Provincial drug supervision and management departments shall supervise and urge the holders of drug marketing authorizations for the above-mentioned drugs in the administrative region to do a good job of revising the corresponding instructions and replacing labels and instructions in accordance with the requirements, and strictly investigate and deal
with violations of laws and regulations in accordance with law.
This is hereby announced
.
Accessories: 1.
Hydroxyethyl starch 20 sodium chloride injection, hydroxyethyl starch 40 sodium chloride injection, hypertonic sodium chloride hydroxyethyl starch 40 injection, hydroxyethyl starch 200/0.
5 sodium chloride injection, hypertonic hydroxyethyl starch 200/0.
5 sodium chloride injection, hydroxyethyl starch 130/0.
4 sodium chloride injection instructions safety content revision requirements 2.
Hydroxyethyl starch 130/0.
4 electrolyte injection instructions Safety content revision requirements State Food and Drug Administration September 2, 2022 Annex 1 Hydroxyethyl starch 20 sodium chloride injection, hydroxyethyl starch 40 sodium chloride injection, hypertonic sodium chloride hydroxyethyl starch 40 injection, hydroxyethyl starch 200/0.
5 sodium chloride injection, hypertonic hydroxyethyl starch 200/0.
5 sodium chloride injection, hydroxyethyl starch 130/0.
4 sodium chloride injection Instructions Safety content revision requirements Note: The instructions must include and are not limited to the following I.
[Warning Words] In adult critically ill patients, including sepsis patients, The use of hydroxyethyl starch increases the risk of: l death l renal replacement therapy For adult critically ill patients, including patients with sepsis, the use of hydroxyethyl starch
is contraindicated.
Second, [adverse reactions] In the infusion process, if the patient has an intolerable reaction, the administration should be terminated immediately and appropriate treatment
should be given.
Adverse reactions are: very common (1/10 ≥), common (≥ 1/100 and < 1/10), uncommon (≥ 1/1,000 and < 1/100), rare (≥ 1/10,000 and < 1/1,000), extremely rare (< 1/10,000), unknown (available data can not be estimated).

。 Abnormalities of the blood and lymphatic system According to the literature, B.
Braun Melsungen AG products are common (dose-related): a decrease in the specific capacity of blood cells, a decrease in the concentration of plasma proteins; Common: dilution of coagulation factors, prolonged bleeding time and aPTT, decreased
levels of FVIII/vWF complexes.
Fresenius Kabi Deutschland GmbH products are rare (used in large doses): dose-related coagulation abnormalities
.
Immune system abnormalities are rare: allergic /anaphylactoid reactions (allergies, mild flu-like symptoms, bradycardia, tachycardia, bronchospasm, non-cardiac pulmonary edema).

During the use of this product, if an allergic reaction occurs, the infusion should be stopped immediately and appropriate treatment measures should be taken until the symptoms disappear
.
Abnormalities of the skin and subcutaneous tissues Itching
of the skin.
(According to the literature, this adverse reaction is common in Fresenius Kabi Deutschland GmbH products, B.
Braun Melsungen AG products are uncommon) Renal and urinary system abnormalities The frequency is unknown: kidney damage
.
Hepatobiliary abnormalities the frequency is unknown: liver damage
.
Laboratory abnormalities are common (dose-dependent): serum amylase concentrations may be elevated, interfering with the diagnosis
of pancreatitis.
Elevated amylase is due to the formation of a complex of amylase with hydroxyethyl starch, which delays the metabolism of amylase and should not be diagnosed as pancreatitis
.
When used in high doses, the corresponding blood components such as coagulation factors, plasma proteins, and hematocrit are reduced
due to the blood thinning effect.
(According to the literature, this adverse reaction is common in Fresenius Kabi Deutschland GmbH products, B.
Braun Melsungen AG products are common) There have also been reports of
anemia, erythrocytopenia, respiratory insufficiency, bleeding after treatment, and bleeding from trauma.
Information about specific adverse reactions Anaphylaxis / anaphylactoid reactions After administration of hydroxyethyl starch, various degrees of anaphylactoid reactions independent of the dose may occur
.
Therefore, all patients receiving starch infusions should be closely monitored for anaphylactic / anaphylactoid reactions
.
If anaphylactic/anaphylactic reactions occur, the infusion should be discontinued immediately and general emergency treatment
initiated.
It is not possible to predict by trial which patients will develop anaphylactic/anaphylactoid reactions, nor can it predict the course and severity of such reactions
.
Prophylaxis with corticosteroids has not been shown to have a preventive effect
.
3.
[Contraindications] - Those who are
allergic to any of the ingredients in this product.
- For adult critically ill patients, including patients with sepsis, the use of hydroxyethyl starch products
is prohibited.
Because in such patients, the use of hydroxyethyl starch increases the risk
of death and renal replacement therapy.
- Burns - Renal insufficiency or renal replacement therapy (eg, undergoing dialysis treatment) - Intracranial or cerebral hemorrhage - Critically ill patients (especially those in intensive care (ICU)) - Fluid overload - Pulmonary edema - Dehydration - Severe hypernatremia or hyperchloremia - Severe liver function impairment - Congestive heart failure - Pre-existing coagulation disorders or bleeding disorders - Organ transplant patients IV.
[Precautions] The marketing authorization holder or manufacturer of this product should target the applicable population of this product, Users are trained
in limited content such as contraindicated groups.
General Precautions: Patients should be closely monitored and infused
slowly because of the risk of hypersensitivity reactions (allergies and allergies).
Surgery and trauma: Long-term data on the safe use of hydroxyethyl starch in surgical and trauma patients are insufficient
.
The expected benefits of treatment should be carefully weighed against uncertainty about long-term safety
.
Alternative treatment options should be considered
.
The use of hydroxyethyl starch for volume replacement must be carefully considered and volume and dose control
should be performed using hemodynamic monitoring.
Adequate fluid intake must be ensured
.
If severe dehydration occurs, a crystalline solution
should be given first.
Capacity overload
due to overdose or infusion must be avoided.
The dose should be carefully adjusted at the time of use, especially in patients with lung and cardiac circulatory diseases
.
Avoid overloading of fluids, and for patients with cardiac insufficiency, the dose
should be adjusted.
Serum electrolytes, fluid balance, and renal function should be closely monitored
.
Electrolyte and fluid replacement therapy
is carried out according to the individual needs.
When there are signs of kidney damage, it is necessary to stop the drug
immediately.
Monitoring
of renal function is recommended.
Renal function should be continuously monitored for at least 90 days in hospitalized patients, as renal replacement therapy has been reported
for up to 90 days after the infusion of hydroxyethyl starch.
Special caution
should be exercised in the use of this product in patients with impaired liver function.
With this product, liver function
should be monitored.
Severe hemodilution
caused by the use of hydroxyethyl starch solution in high doses in patients with hypovolemia must be avoided.
When repeated administration, coagulation parameters
should be closely monitored.
Discontinue the drug
immediately when coagulation dysfunction occurs.
Because of the increased risk of bleeding, exoccupation is not recommendedHydroxyethyl starch
is used in patients undergoing open-heart surgery.
The use of this product in high doses can lead to blood thinning, which may encourage bleeding in patients with traumatic hemorrhage
.
Special attention should be paid to the medication in patients with electrolyte abnormalities, such as those
with hyperkalemia, hypernatremia, hypermagnesium, and hyperchloroemia.
Literature reports: 1.
There are reports that in clinical trials conducted abroad, the administration of hydroxyethyl starch preparations to patients with severe sepsis, compared with the administration of Ringer acetate liquid, the risk of death increased at 90 days after administration, and the proportion of patients requiring renal replacement therapy increased
.
When hydroxyethyl starch was given to ICU admitted patients (including patients with sepsis), the risk of death did not increase as of 90 days after administration compared with normal saline administration, and the proportion of patients requiring renal replacement therapy increased
.
2.
There are reports that in clinical trials conducted abroad, when fluid management is administered during heart surgery using artificial heart and lung in adults, hydroxyethyl starch is given, compared with the administration of albumin, the risk of postoperative bleeding that requires blood transfusion and the need for re-operation due to bleeding is increased
.
Effects on laboratory tests: When hydroxyethyl starch solution is administered, it may cause a transient increase in serum amylase levels, which can interfere with the diagnosis
of pancreatitis.
Mistake this phenomenon for pancreatic injury
should be avoided.
Other: Without compatibility studies, this product cannot be mixed with other drugs
.
The bag should be used
immediately after opening.
Cannot be used after expiry date; For single use only, unused medicines should be discarded
.
This product needs to be administered immediately after the infusion container is connected to the infusion
device.
Containers that are partially used must not be reconnected
.
Use
only when the solution is clear and the container is not damaged.
Keep out of reach of children
.
During the use of this product, if any adverse events and / or adverse reactions occur, the infusion should be discontinued and consult a doctor
.
Please inform your doctor
about other medicines at the same time.
Exercisers should use with
caution.
V.
[Medication for pregnant and lactating women] Pregnant women Have not carried out randomized controlled clinical trials
of hydroxyethyl starch in pregnant women.
If pregnant women receiving hydroxyethyl starch develop anaphylactoid / anaphylactoid reactions, it can have an adverse effect on
the fetus.
This product
should be used in pregnancy only if the potential benefit to the fetus outweighs the possible risk.
Especially when using this product in
the first trimester of pregnancy.
Special care must be taken to avoid hypervolemia caused by overdose leading to pathological hemodilution and fetal hypoxia
.
Breastfeeding Is uncertain whether hydroxyethyl starch can be secreted through breast milk and should be used
with caution in lactating women.
If you must use this product, you can consider temporarily stopping breastfeeding
.
Sixth, [children's medication] The research data on children's medication is limited, and the safety and effectiveness have not been established, so the use of hydroxyethyl starch products in this category of population is
not recommended 。 A European multicenter prospective post-marketing safety observation study (PASS) was used to evaluate
children under 12 years of age who were undergoing surgery (n=1130) using Venofundin 6% (6% hydroxyethyl starch 130/0.
42 sodium chloride injection) and Tetraspan 6% (hydroxyethyl starch 130/0.
42 electrolyte injection).
The safety of
hydroxyethyl starch use in pediatric patients during surgery was evaluated by possible adverse reactions, acid-base balance, electrolyte and hemoglobin changes.
No serious or important adverse drug reactions
directly associated with hydroxyethyl starch were observed.
The incidence of adverse reactions was dose-related, but it could not be proven to be age-related
.
Conclusion: The use of doses up to 20 mL/kg body weight during surgery appears to be safe
for pediatric patients.
In one trial, newborns undergoing elective surgery and infants under 2 years of age were randomized to Voluven® (6% hydroxyethyl starch 130/0.
4 sodium chloride injection) (N=41) or 5% albumin (N=41).

The average dose given to Voluven® is 16±9 mL/kg
.
In another trial, children aged 2–12 who underwent heart surgery were randomly enrolled in Voluven® (N=31) or 5% albumin (N=30).

The average dose given to Voluven® was 36±11 mL/kg
.
However, medication according to the above data is not recommended
.
VII.
[Geriatric Drugs] There are no clinical trials
for the use of drugs for elderly patients.
Of the participants in the 6% hydroxyethyl starch 130/0.
4 — 0.
9% sodium chloride injection clinical trial (N = 471), 32% of the subjects were ≥ 65 years old and 7% were ≥ 75 years.

Between these subjects and young subjects, no overall difference
in the safety or efficacy of this product was found.
Other reported clinical experiences have also not found significant differences between older and younger patients, but some older patients should not be overlooked for greater
sensitivity to the drug.
In general, the physiological function of elderly patients is reduced, and attention should be paid to reducing the
dose.
VIII.
[Drug Interaction] Combined with nephrotoxic drugs: The combination of hydroxyethyl starch solution and potential nephrotoxic drugs, such as aminoglycosides, may enhance adverse reactions to the kidneys
.
Combined with drugs that cause sodium retention: Since this product itself contains sodium, it is necessary to consider
carefully when co-administering with drugs that cause sodium retention.
IX.
[Drug Overdose] Symptoms The overdose of this product will lead to unexpected hypervolemia and circulatory overload, causing a significant decrease in
hematocrit and plasma proteins.
These may be associated
with heart and lung injury (pulmonary edema).
Overdose can lead to electrolyte abnormalities (eg, hyperchloremia) and acid-base balance disorders (perchlorous acidosis
).
Once treatment occurs, the infusion should be stopped immediately and diuretics
should be considered.
Symptomatic treatment and monitoring of electrolytes
.
(Note: If the security content of the original approval specification is more comprehensive or stricter than the requirements of this revision, the original approved content
shall be retained.
) If other contents of the specification are inconsistent with the above revision requirements, they shall be revised
together.
Annex 2 Hydroxyethyl starch 130/0.
4 Electrolyte Injection Instructions Safety Content Revision Requirements Note: The instructions must include and are not limited to the following I.
[Warning Words] In adult critically ill patients, including sepsis patients, the use of hydroxyethyl starch will increase the following risks: l Death l Renal replacement therapy For adult critically ill patients, including sepsis patients, the use of hydroxyethyl starch
is prohibited.
Second, [adverse reactions] In the infusion process, if the patient has an intolerable reaction, the administration should be terminated immediately and appropriate treatment
should be given.
Adverse reactions are: very common (≥1/10), common (≥ 1/100 and < 1/10), uncommon (≥ 1/1,000 and < 1/100), rare (≥ 1/10,000 and < 1/1,000), extremely rare (< 1/10,000), unknown (available data can not be estimated).

。 Abnormalities of the blood and lymphatic system According to the literature, B.
Braun Melsungen AG products are common (dose-related): a decrease in the specific capacity of blood cells, a decrease in the concentration of plasma proteins; Common: dilution of coagulation factors, prolonged bleeding time and aPTT, decreased
levels of FVIII/vWF complexes.
Fresenius Kabi Deutschland GmbH products are rare (used in large doses): dose-related coagulation abnormalities
.
Immune system abnormalities are rare: allergic /anaphylactoid reactions (allergies, mild flu-like symptoms, bradycardia, tachycardia, bronchospasm, non-cardiac pulmonary edema).

During the use of this product, if an allergic reaction occurs, the infusion should be stopped immediately and appropriate treatment measures should be taken until the symptoms disappear
.
Abnormalities of the skin and subcutaneous tissues Itching
of the skin.
(According to the literature, this adverse reaction is common in Fresenius Kabi Deutschland GmbH products, B.
Braun Melsungen AG products are uncommon) Renal and urinary system abnormalities The frequency is unknown: kidney damage
.
Hepatobiliary abnormalities the frequency is unknown: liver damage
.
Laboratory abnormalities are common (dose-dependent): serum amylase concentrations may beElevated, interferes with the diagnosis
of pancreatitis.
Elevated amylase is due to the formation of a complex of amylase with hydroxyethyl starch, which delays the metabolism of amylase and should not be diagnosed as pancreatitis
.
When used in high doses, the corresponding blood components such as coagulation factors, plasma proteins, and hematocrit are reduced
due to the blood thinning effect.
(According to the literature, this adverse reaction is common in Fresenius Kabi Deutschland GmbH products, B.
Braun Melsungen AG products are common) There have also been reports of
anemia, erythrocytopenia, respiratory insufficiency, bleeding after treatment, and bleeding from trauma.
Information about specific adverse reactions Anaphylaxis / anaphylactoid reactions After administration of hydroxyethyl starch, various degrees of anaphylactoid reactions independent of the dose may occur
.
Therefore, all patients receiving starch infusions should be closely monitored for anaphylactic / anaphylactoid reactions
.
If anaphylactic/anaphylactic reactions occur, the infusion should be discontinued immediately and general emergency treatment
initiated.
It is not possible to predict by trial which patients will develop anaphylactic/anaphylactoid reactions, nor can it predict the course and severity of such reactions
.
Prophylaxis with corticosteroids has not been shown to have a preventive effect
.
3.
[Contraindications] - Those who are
allergic to any of the ingredients in this product.
- For adult critically ill patients, including patients with sepsis, the use of hydroxyethyl starch products
is prohibited.
Because in such patients, the use of hydroxyethyl starch increases the risk
of death and renal replacement therapy.
- Burns - Renal insufficiency or renal replacement therapy (eg, undergoing dialysis treatment) - Intracranial or cerebral hemorrhage - Critically ill patients (especially those in intensive care (ICU)) - Fluid overload - Pulmonary edema - Dehydration - Severe hypernatremia or hyperchloremia - Hyperkalemia - Severe liver damage - Congestive heart failure - Pre-existing coagulation disorders or bleeding disorders - Organ transplant patients IV.
[Precautions] The marketing authorization holder or manufacturer of this product should target the applicable population of this product, Users are trained
in limited content such as contraindicated groups.
General Precautions: Patients should be closely monitored and infused
slowly because of the risk of hypersensitivity reactions (allergies and allergies).
Surgery and trauma: Long-term data on the safe use of hydroxyethyl starch in surgical and trauma patients are insufficient
.
The expected benefits of treatment should be carefully weighed against uncertainty about long-term safety
.
Alternative treatment options should be considered
.
The use of hydroxyethyl starch for volume replacement must be carefully considered and volume and dose control
should be performed using hemodynamic monitoring.
Adequate fluid intake must be ensured
.
If severe dehydration occurs, a crystalline solution
should be given first.
Capacity overload
due to overdose or infusion must be avoided.
The dose should be carefully adjusted at the time of use, especially in patients with lung and cardiac circulatory diseases
.
Avoid overloading of fluids, and for patients with cardiac insufficiency, the dose
should be adjusted.
Serum electrolytes, fluid balance, and renal function should be closely monitored
.
Electrolyte and fluid replacement therapy
is carried out according to the individual needs.
When there are signs of kidney damage, it is necessary to stop the drug
immediately.
Monitoring
of renal function is recommended.
Renal function should be continuously monitored for at least 90 days in hospitalized patients, as renal replacement therapy has been reported
for up to 90 days after the infusion of hydroxyethyl starch.
Special caution
should be exercised in the use of this product in patients with impaired liver function.
With this product, liver function
should be monitored.
Severe hemodilution
caused by the use of hydroxyethyl starch solution in high doses in patients with hypovolemia must be avoided.
When repeated administration, coagulation parameters
should be closely monitored.
Discontinue the drug
immediately when coagulation dysfunction occurs.
Because of the increased risk of bleeding, the use of hydroxyethyl starch
in patients undergoing cardiac open-view surgery for cardiopulmonary bypass is not recommended.
The use of this product in high doses can lead to blood thinning, which may encourage bleeding in patients with traumatic hemorrhage
.
Special attention should be paid to the medication in patients with electrolyte abnormalities, such as those
with hyperkalemia, hypernatremia, hypermagnesium, and hyperchloroemia.
Saline-based solutions such as hydroxyethyl starch 130/0.
4 sodium chloride injection are recommended if the patient has metabolic alkalosis or must avoid alkalosis
.
Literature reports: 1.
There are reports that in clinical trials conducted abroad, the administration of hydroxyethyl starch preparations to patients with severe sepsis, compared with the administration of Ringer acetate liquid, the risk of death increased at 90 days after administration, and the proportion of patients requiring renal replacement therapy increased
.
When hydroxyethyl starch was given to ICU admitted patients (including patients with sepsis), the risk of death did not increase as of 90 days after administration compared with normal saline administration, and the proportion of patients requiring renal replacement therapy increased
.
2.
There are reports that in clinical trials conducted abroad, when fluid management is administered during heart surgery using artificial heart and lung in adults, hydroxyethyl starch is given, compared with the administration of albumin, the risk of postoperative bleeding that requires blood transfusion and the need for re-operation due to bleeding is increased
.
Effects on laboratory tests: When hydroxyethyl starch solution is administered, it may cause a transient increase in serum amylase levels, which can interfere with the diagnosis
of pancreatitis.
Mistake this phenomenon for pancreatic injury
should be avoided.
Other: Without compatibility studies, this product cannot be mixed with other drugs
.
If mixing with other drugs is required in special cases, attention should be paid to compatibility (no flocculent or precipitation), sterility and homogeneous mixing
.
The bag should be used
immediately after opening.
Cannot be used after expiry date; For single use only, unused medicines should be discarded
.
This product needs to be administered immediately after the infusion container is connected to the infusion
device.
Containers that are partially used must not be reconnected
.
Use
only when the solution is clear and the container is not damaged.
Keep out of reach of children
.
During the use of this product, if any adverse events and / or adverse reactions occur, the infusion should be discontinued and consult a doctor
.
Please inform your doctor
about other medicines at the same time.
Exercisers should use with
caution.
V.
[Medication for pregnant and lactating women] Pregnant women Have not carried out randomized controlled clinical trials
of hydroxyethyl starch in pregnant women.
If pregnant women receiving hydroxyethyl starch develop anaphylactoid / anaphylactoid reactions, it can have an adverse effect on
the fetus.
This product
should be used in pregnancy only if the potential benefit to the fetus outweighs the possible risk.
Especially when using this product in
the first trimester of pregnancy.
Special care must be taken to avoid hypervolemia caused by overdose leading to pathological hemodilution and fetal hypoxia
.
Breastfeeding Is uncertain whether hydroxyethyl starch can be secreted through breast milk and should be used
with caution in lactating women.
If you must use this product, you can consider temporarily stopping breastfeeding
.
Sixth, [children's medication] The research data on children's medication is limited, and the safety and effectiveness have not been established, so the use of hydroxyethyl starch products in this category of population is
not recommended 。 A European multicenter prospective post-marketing safety observation study (PASS) was used to evaluate
children under 12 years of age who were undergoing surgery (n=1130) using Venofundin 6% (6% hydroxyethyl starch 130/0.
42 sodium chloride injection) and Tetraspan 6% (hydroxyethyl starch 130/0.
42 electrolyte injection).
The safety of
hydroxyethyl starch use in pediatric patients during surgery was evaluated by possible adverse reactions, acid-base balance, electrolyte and hemoglobin changes.
No serious or important adverse drug reactions
directly associated with hydroxyethyl starch were observed.
The incidence of adverse reactions was dose-related, but it could not be proven to be age-related
.
Conclusion: The use of doses up to 20 mL/kg body weight during surgery appears to be safe
for pediatric patients.
In one trial, newborns undergoing elective surgery and under 2 years of age < b1191> infants were randomly enrolled in Voluven® (6% hydroxyethyl starch 130/0.
4 sodium chloride injection) (N=41) or 5% albumin (N=41).

The average dose given to Voluven® is 16±9 mL/kg
.
In another trial, children aged 2–12 who underwent heart surgery were randomly enrolled in Voluven® (N=31) or 5% albumin (N=30).

The average dose given to Voluven® was 36±11 mL/kg
.
However, medication according to the above data is not recommended
.
VII.
[Geriatric Drugs] There are no clinical trials
for the use of drugs for elderly patients.
Of the participants in the 6% hydroxyethyl starch 130/0.
4 to 0.
9% sodium chloride injection clinical trial (N = 471), 32% of the subjects were ≥ 65 years old and 7% of the subjects were ≥ 75 years.

Between these subjects and young subjects, no overall difference
in the safety or efficacy of this product was found.
Other reported clinical experiences have also not found significant differences between older and younger patients, but some older patients should not be overlooked for greater
sensitivity to the drug.
In general, the physiological function of elderly patients is reduced, and attention should be paid to reducing the
dose.
VIII.
[Drug Interaction] Combined with nephrotoxic drugs: The combination of hydroxyethyl starch solution and potential nephrotoxic drugs, such as aminoglycosides, may enhance adverse reactions to the kidneys
.
Combined with drugs that cause sodium retention: Since this product itself contains electrolytes, it is necessary to consider
carefully when co-administering with drugs that cause potassium and sodium retention.
IX.
[Drug Overdose] Symptoms The overdose of this product will lead to unexpected hypervolemia and circulatory overload, causing a significant decrease in
hematocrit and plasma proteins.
These may be associated
with heart and lung injury (pulmonary edema).
Overdose can lead to electrolyte abnormalities (eg, hyperchloremia) and acid-base balance disorders (perchlorous acidosis
).
Once treatment occurs, the infusion should be stopped immediately and diuretics
should be considered.
Symptomatic treatment and monitoring of electrolytes
.
(Note: If the security content of the original approval specification is more comprehensive or stricter than the requirements of this revision, the original approved content
shall be retained.
) If other contents of the specification are inconsistent with the above revision requirements, they shall be revised
together.
Appendix 1 of Adverse Reactions to Drug Registration, [Warning] II, [Adverse Reactions] III, [Contraindications] IV, [Precautions] Adverse Drug Reaction Exercise V, [Medication for Pregnant and Lactating Women] VI, [].
Pediatric medication for children】 Infant VII, [Geriatric medication] VIII, [Drug Interaction] 9, [Drug Overdose] Annex 2 Hydroxyethyl Starch 130/0.
4 Electrolyte Injection Instructions Safety Content Revision Requirements I, [Warning Words] II, [Adverse Reactions] III, [Contraindications] IV, [Precautions] Adverse Drug Reactions Exercise V.
[Medication for Pregnant and Lactating Women] VI.
[Medication for Children and Children] Infant VII, [Medication for the Elderly] VIII, [Drug Interaction] 9, [Drug Overdose]