SODIUM CHLORIDE 0.9% Solution for infusion Ref.[8051] Active ingredients: Sodium chloride

Fluid balance/renal function

Use in patients with (severe) renal impairment

Sodium Chloride 0.9% should be administered with particular caution to patients with or at risk of severe renal impairment. In such patients, administration of Sodium Chloride 0.9% may result in sodium retention. (See “Use in patients at risk for sodium retention, fluid overload and oedema” below; for additional considerations.)

Risk of fluid and/or solute overload and electrolyte disturbances

Depending on the volume and rate of infusion, intravenous administration of Sodium Chloride 0.9% can cause:

• Fluid and/or solute overload resulting in overhydration/hypervolemia and, for example, congested states, including central and peripheral oedema.
• Clinically relevant electrolyte disturbances and acid-base imbalance.

In general, the risk of dilutional states (retention of water relative to sodium) is inversely proportional to the electrolyte concentrations of Sodium Chloride 0.9% and its additions. Conversely, the risk of solute overload causing congested states (retention of solute relative to water) is directly proportional to the electrolyte concentrations of Sodium Chloride 0.9% and its additions.

Special clinical monitoring is required at the beginning of any intravenous infusion. Clinical evaluation and periodic laboratory determinations may be necessary to monitor changes in fluid balance, electrolyte concentrations, and acid-base balance during prolonged parenteral therapy or whenever the condition of the patient or the rate of administration warrants such evaluation.

High volume infusion must be used under specific monitoring in patients with cardiac or pulmonary failure and in patients with non-osmotic vasopressin release (including SIADH), due to the risk of hospital-acquired hyponatraemia (see below).

Hyponatraemia

Patients with non-osmotic vasopressin release (e.g. in acute illness, pain, post-operative stress, infections, burns, and CNS diseases), patients with heart-, liver- and kidney diseases and patients exposed to vasopressin agonists (see section 4.5) are at particular risk of acute hyponatraemia upon infusion of hypotonic fluids.

Acute hyponatraemia can lead to acute hyponatraemic encephalopathy (cerebral oedema) characterized by headache, nausea, seizures, lethargy and vomiting. Patients with cerebral oedema are at particular risk of severe, irreversible and life-threatening brain injury.

Children, women in the fertile age and patients with reduced cerebral compliance (e.g. meningitis, intracranial bleeding, cerebral contusion and brain oedema) are at particular risk of the severe and life-threatening brain swelling caused by acute hyponatraemia.

Use in patients at risk for sodium retention, fluid overload and oedema

Sodium Chloride 0.9% should be used with particular caution, if at all, in patients with or at risk for:

• Hypernatraemia. Rapidly correcting hypernatraemia once adaptation has occurred may lead to cerebral oedema, potentially resulting in seizures, permanent brain damage, or death.
• Hyperchloraemia
• Metabolic acidosis, which may be worsened by prolonged use of this product, especially in patients with renal impairment.
• Hypervolaemia such as congestive heart failure and pulmonary oedema may be precipitated, particularly in patients with cardiovascular disease.
• Iatrogenic hyperchloraemic metabolic acidosis (e.g., during intravenous volume resuscitation)
• Conditions that may cause sodium retention, fluid overload and oedema (central and peripheral), such as patients with
  • primary hyperaldosteronism,
  • secondary hyperaldosteronism, associated with, for example,
    • hypertension,
    • congestive heart failure,
    • liver disease (including cirrhosis),
    • renal disease (including renal artery stenosis, nephrosclerosis) or pre-eclampsia.

Medications that may increase the risk of sodium and fluid retention, such as corticosteroids

Infusion reactions

Symptoms of unknown aetiology which can appear to be hypersensitivity reactions have been reported very rarely in association with infusion of Sodium Chloride 0.9 %. These have been characterized as hypotension, pyrexia, tremor, chills, urticaria, rash and pruritus. Stop the infusion immediately if signs or symptoms of these reactions develop. Appropriate therapeutic countermeasures should be instituted as clinically indicated.

Specific patient groups

The consulting physician should be experienced in this product’s use and safety in these special populations that are especially sensitive to rapid changes in serum sodium levels.

Rapid correction of hyponatraemia and hypernatraemia is potentially dangerous (risk of serious neurologic complications). See section “Hyponatraemia/hypernatraemia” above.

Paediatric population

Plasma electrolyte concentrations should be closely monitored in the paediatric population as this population may have impaired ability to regulate fluids and electrolytes. Repeated infusions of sodium chloride should therefore only be given after determination of the serum sodium level.

Geriatric population

When selecting the type of infusion solution and the volume/rate of infusion for a geriatric patient, consider that geriatric patients are generally more likely to have cardiac, renal, hepatic, and other diseases or concomitant drug therapy.

For information on preparation of the product and additives, please see section 6.6.

Drugs leading to an increased vasopressin effect

The below listed drugs increase the vasopressin effect, leading to reduced renal electrolyte free water excretion and may increase the risk of hospital acquired hyponatraemia following inappropriately balanced treatment with i.v. fluids (see sections 4.2, 4.4 and 4.8).

• Drugs stimulating vasopressin release include: Chlorpropamide, clofibrate, carbamazepine, vincristine, selective serotonin reuptake inhibitors, 3.4-methylenedioxy-N-methamphetamine, ifosfamide, antipsychotics, narcotics
• Drugs potentiating vasopressin action include: Chlorpropamide, NSAIDs, cyclophosphamide
• Vasopressin analogues include: Desmopressin, oxytocin, terlipressin

Other medicinal products increasing the risk of hyponatraemia also include diuretics in general and antiepileptics such as oxcarbazepine.

Caution is advised in patients treated with lithium. Renal sodium and lithium clearance may be increased during administration of Sodium Chloride 0.9%. Administration of Sodium Chloride 0.9% may result in decreased lithium levels.

Corticoids/Steroids and carbenoxolone, are associated with the retention of sodium and water (with oedema and hypertension). See Section 4.4 Special warnings and precautions for use.

There are no adequate data from the use of Sodium Chloride 0.9% in pregnant or lactating women. The physician should carefully consider the potential risks and benefits for each specific patient before administering Sodium Chloride 0.9%.

Sodium Chloride 0.9% should be administrated with special caution for pregnant women during labour particularly as to serum-sodium if administered in combination with oxytocin (see section 4.4, 4.5 and 4.8).

Caution is advised with patients with pre-eclampsia (See Section 4.4. Special warnings and precautions for use).

When a medicinal product is added, the nature of the drug and its use during pregnancy and lactation has to be considered separately.

No studies have been conducted on the influence of Sodium Chloride 0.9% on the ability to operate an automobile or other heavy machinery.

The following adverse reactions have been reported in post-marketing experience. The frequency of the adverse drug reactions listed in this section cannot be estimated from the available data.

Nervous system disorders

Not known: Tremor, Acute hyponatraemic encephalopathy*

Metabolism and nutrition disorders

Not known: Hospital acquired hyponatraemia*

Vascular disorders

Not known: Hypotension

Skin and subcutaneous tissue disorders

Not known: Urticaria, Rash, Pruritus

General disorders and administration site conditions

Not known: Infusion site reactions, such as: Infusion site erythema, Vein irritation, Injection site streaking, burning sensation, Local pain or reaction , Infusion site urticaria, Infection at the site of injection, Venous thrombosis or phlebitis extending from the site of injection, extravasation and hypervolemia, Pyrexia, Chills

* Hospital acquired hyponatraemia may cause irreversible brain injury and death, due to development of acute hyponatraemic encephalopathy, frequency unknown (see sections 4.2. 4.4, 4.5).

The following adverse reactions have not been reported with this product but may occur:

• Hypernatraemia (eg. when administered to patients with nephrogenic diabetes insipidus or high nasogastric output)
• Hyperchloraemic metabolic acidosis
• Hyponatraemia, which may be symptomatic. Hyponatraemia may occur when normal free water excretion is impaired. (eg SIADH or postoperative)

General adverse effects of sodium excess are described in section 4.9 Overdose.

Additives

When Sodium Chloride 0.9% is used as a diluent for injectable preparations of other drugs, the nature of additives will determine the likelihood of any other undesirable effect.

If an adverse event occurs the patient should be evaluated and appropriate counter measures be started, if needed the infusion should be stopped. The remaining part of the solution should be kept for investigation if deemed necessary.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard.

As with all parenteral solutions compatibility of the additives with the solution must be assessed before addition. In the absence of compatibility studies, this solution must not be mixed with other medicinal products. Those additives known to be incompatible should not be used.

See section 6.6 for further instructions on the use of the product with additives.