INSTRUCTION

for medical use of the medicinal product

 

SOLEN

 

Composition:

active substance: sodium chloride;

100 ml of solution contain 0.9 g of sodium chloride;

excipients: water for injection.

 

Pharmaceutical form. Solution for infusion.

Basic physical and chemical properties: clear colourless solution.

 

Pharmacotherapeutic group. Blood substitutes and perfusion solutions. Electrolyte solutions. ATC code В05Х А03.

 

Pharmacological properties.

Pharmacodynamics.

Sodium Chloride 0.9% intravenous infusion is an isotonic solution, with an approximate osmolarity of 308 mOsm/l.

The pharmacodynamic properties of the solution are those of the sodium and chloride ions in maintaining the fluid and electrolyte balance. Ions, such as sodium, circulate through the cell membrane, using various mechanisms of transport, including the sodium pump (Na-K-ATPase). Sodium plays an important role in neurotransmission, cardiac electrophysiology and the renal metabolism as well.

Pharmacokinetics.

Sodium is predominantly excreted by the kidney, but there is extensive renal reabsorption.

Small amounts of sodium are observed in the faeces and sweat.

 

Clinical particulars.

Indications.

Isotonic dehydration.

Sodium depletion.

Vehicle or diluent of compatible drugs.

 

Contraindications.

The solution is contraindicated in patient with hypernatraemia or hyperchloraemia.

The contraindications related to the added medicinal product should be considered.

 

Interaction with other medicinal products and other forms of interaction.

Drugs causing an increased vasopressin effect

The below listed drugs increase the vasopressin effect, leading to reduced renal electrolyte excretion and may increase the risk of hospital acquired hyponatraemia following inappropriately balanced treatment with intravenous fluids.

• Drugs stimulating vasopressin release: chlorpropamide, clofibrate, carbamazepine, vincristine, selective serotonin reuptake inhibitors, 3.4-methylenedioxy-N-methamphetamine, ifosfamide, antipsychotics, narcotics.
• Drugs potentiating vasopressin action: chlorpropamide, NSAIDs, cyclophosphamide.
• Vasopressin analogues: 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).

 

Precautions for use.

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.

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 hyperhydration/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 hyponatraemia.

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 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 extreme caution in patients at risk of:

• 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) in patients with:
• Ø primary hyperaldosteronism,
• Ø 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, such as corticosteroids, that may increase the risk of sodium and fluid retention.

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).

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.

Elderly

When selecting the type of infusion solution and the volume/rate of infusion for elderly patients, it is necessary to take into account that elderly patients are generally more likely to have cardiac, renal, hepatic, and other diseases or concomitant drug therapy.

 

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.

Caution is advised with patients with pre-eclampsia.

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

 

Effects on ability to drive and use machines.

No studies have been conducted on the influence of sodium chloride 0.9% on the ability to drive vehicles or operate other machines.

 

Method of administrations and dosage.

Adults, elderly and children

Doses may be expressed in terms of mEq or mmol of sodium, mass of sodium, or mass of sodium salt (1 g NaCl = 394 mg, 17.1 mEq or 17.1 mmol of Na and Cl).

Fluid balance, serum electrolytes and acid-base balance should 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 hyponatremia. Monitoring of serum sodium is particularly important for hypotonic fluids.

Theoretical osmolarity of sodium chloride 0.9% for intravenous infusion is 308 mOsm/l.

The rate and volume of infusion depend on the individual patient's condition.

Treatment of isotonic dehydration:

• For adults: 500 ml to 3 litres/24 h.
• For infants and children: 20 to 100 ml per 24 h and per kg of body weight, depending of the age and the total body mass.

The recommended dosage when used as a diluent ranges from 50 to 250 ml per dose of medicinal product to be administered.

 

Children.

Children with isotonic dehydration and sodium depletion should be administered 20 to 100 ml/kg body weight/day, depending on age and body weight.

Plasma electrolytes should be closely monitored because the ability to regulate water-electrolyte balance in paediatric patients may be reduced. Repeated infusion of sodium chloride should be performed only after determination of serum sodium levels.

 

Overdose.

General adverse effects of sodium excess in the body include nausea, vomiting, diarrhea, abdominal cramps, thirst, reduced salivation and lacrimation, sweating, fever, tachycardia, hypertension, 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 0.9% is used as a diluent for injectable preparations of other drugs, the signs and symptoms of over infusion will be related to the nature of the additives being used. In the event of accidental over infusion, treatment should be discontinued and the patient should be observed for the appropriate signs and symptoms related to the drug administered. The relevant measures should be provided as necessary.

 

 

Adverse reactions.

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.

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.

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).

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 adverse reaction.

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.

 

Shelf life.

3 years.

In-use shelf life: Additives.

Chemical and physical stability of any additive at the pH of sodium chloride 0.9% intravenous infusion should be established prior to use.

From a microbiological point of view, the diluted product must be used immediately unless dilution has taken place in controlled and validated aseptic conditions. If not used immediately, in-use storage times and conditions are the responsibility of the user.

 

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °С.

Keep out of reach of children.

 

Incompatibilities.

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.

 

Packaging.

100 ml of preparation in a container. 1 film-coated container in a box.

 

Terms of dispensing.

On prescription.

 

Manufacturer.

Eurolife Healthcare Pvt. Ltd.

 

Manufacturer’s registered address.

Khasra No. 520, Bhagwanpur, Roorkee, Haridwar, India.

 

Applicant.

Ananta Medicare Ltd.

 

Applicant’s and/or applicant’s representative registered address.

Suite 1, 2 Station Court, Imperial Wharf, Townmead Road, Fulham, London, United Kingdom.

 

Date of last update. 08.07.20