4.1. Therapeutic indications

• For use in prophylactic and replacement therapy, requiring the use of isotonic saline solution.

• As a vehicle or diluent for compatible drugs for parenteral administration.

• As a saline irrigant.

• As a priming fluid for haemodialysis procedures and to initiate and terminate blood transfusions.

4.2. Posology and method of administration

Posology

Fluid balance, serum electrolytes and acid-base balance may need to be monitored before and during administration, with particular attention to serum sodium in patients with increased non-osmotic vasopressin release (syndrome of inappropriate antidiuretic hormone secretion, SIADH) and in patients co-medicated with vasopressin agonist drugs, due to the risk of hospital-acquired hyponatraemia (see sections 4.4, 4.5 and 4.8).

Monitoring of serum sodium is particularly important for hypotonic fluids.

The infusion rate and volume depend on the age, weight, clinical condition (e.g. burns, surgery, head-injury, infections), and concomitant therapy should be determined by the consulting physician experienced in paediatric intravenous fluid therapy (see sections 4.4. and 4.8).

When Sodium Chloride Injection BP 0.9% w/v is used as a diluent for injectable preparations of other drugs, the dosage and the infusion rate will also be dictated by the nature and the dose regimen of the prescribed drug.

Method of administration

Sodium Chloride Injection BP 0.9% w/v may be administered via intravenous, intramuscular or subcutaneous injection or via intravenous infusion.

When Sodium Chloride Injection BP 0.9% w/v is used for the preparation of other medicinal products, the method of administration will be determined by the prescribing information of the medicinal product being diluted.

4.3. Contraindications

Sodium Chloride Injection BP 0.9% w/v is contraindicated in patients presenting hypernatraemia or hyperchloraemia.

The contra-indications related to the added medicinal product should be considered.

4.4. Special warnings and precautions for use

Fluid balance/renal function

Use in patients with (severe) renal impairment

Sodium chloride 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 infusions 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:

o primary hyperaldosteronism,

o secondary hyperaldosteronism, associated with, for example:

- hypertension,

- congestive heart failure,

- liver disease (including cirrhosis),

- renal disease (including renal artery stenosis, nephrosclerosis) or pre-eclampsia.

Sodium chloride should also be used with particular caution, if at all, in patients in receipt of 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.

4.5. Interaction with other medicinal products and other forms of interaction

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 intravenous 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 are associated with the retention of sodium and water (with oedema and hypertension). See section 4.4.

4.6. Fertility, pregnancy and lactation

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 sections 4.4, 4.5 and 4.8).

Caution is advised with patients with pre-eclampsia (See section 4.4).

When sodium chloride 0.9% is used in combination with another medicinal product, the nature of the other medicinal product and its use during pregnancy and lactation has to be considered separately.

4.7. Effects on ability to drive and use machines

None known.

4.8. Undesirable effects

The following adverse reactions have been reported for sodium chloride 0.9%. The frequency of the adverse drug reactions listed in this section cannot be estimated from the available data.

System Organ Class (SOC)

Adverse reactions (Preferred Term)

Frequency

Nervous system disorders

Tremor

Acute hyponatraemic encephalopathy*

Not known

Metabolism and nutrition disorders

Hospital acquired hyponatraemia*

Not known

Vascular disorders

Hypotension

Not known

Skin and subcutaneous tissue disorders

Urticaria

Rash

Pruritus

Not known

General disorders and administration site conditions:

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

Not known

* 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 (e.g. 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. (e.g. SIADH or postoperative)

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

Use in combination with other medicinal products

When Sodium Chloride Injection BP 0.9% w/v is used in the preparation of other medicinal products, the nature of the other medicinal product will determine the likelihood of any other undesirable effects.

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 at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

General adverse effects of sodium chloride excess in the body include: nausea, vomiting, diarrhoea, abdominal cramps, thirst, reduced salivary and lachrymal secretions, sweating, fever, hypotension or hypertension, tachycardia, renal failure, peripheral and pulmonary oedema, respiratory arrest, headache, dizziness, restlessness, irritability, weakness, muscular twitching and rigidity, convulsions, coma and death.

An excessive volume of sodium chloride 0.9% may lead to hypernatraemia (which can lead to CNS manifestations, including seizures, coma, cerebral oedema and death) and sodium overload (which can lead to central and/or peripheral oedema) and should be treated by an attending specialised physician.

Excess chloride in the body may cause a loss of bicarbonate, with an acidifying effect.

When Sodium Chloride Injection BP 0.9% w/v is used in the preparation of other medicinal products, the signs and symptoms of overdose will be related to the nature of the other medicinal product used. In the event of accidental overdose, treatment should be discontinued and the patient should be observed for the appropriate signs and symptoms related to the medicinal product administered. The relevant and supportive measures should be provided as necessary.