Restoration of extracellular fluid and electrolyte balances or replacement of extracellular fluid loss where isotonic concentrations of electrolytes are sufficient.

Short-term intravascular volume replacement; (alone or in association with colloid) in case of hypovolemia or hypotension.

Adults the Elderly and Children:

The dosage depends on the age, weight, clinical and biological (acid-base balance) conditions of the patient, and concomitant therapy.

Recommended Dosage:

For adults: 500 ml to 3 Liters / 24h.

For Infants, toddlers and children: 20 ml to 100 ml / kg / 24 h

Administration Rate:

The infusion rate is usually 40 mL/kg/24h in adults.

In pediatric patients the infusion rate is 5 ml/kg/h in average but the value varies with age;

6-8 mL/kg/h for infants,

4-6 mL/kg/h for toddlers,

2-4 mL/kg/h for school children.

In children with burns, the dose is on average 3.4 mL/kg/percent burn at 24 h post-burn and 6.3 mL/kg/per cent burn at 48 h.

In severely head-injured children the dose is on average 2850 mL/m².

Infusion rate and total volume can be higher in surgery or in case of need.

Note:

Infants and toddlers with age ranges from about 28 days to 23 months (a toddler is an infant who can walk).

Children and School Children: Age ranges from about 2 years to 11 years.

Method of Administration:

The administration is performed by intravenous route using sterile and non-pyrogenic

equipment. Refer to section 6.2 – incompatibilities.

High volume infusion must be used under specific monitoring in patients with cardiac or pulmonary failure.

The patient's clinical status and laboratory parameters (blood and urine electrolytes as well as acid-base balance) must be monitored during use of this solution. The plasma potassium level of the patient must be particularly closely monitored in patients at risk of hyperkalaemia.

Solutions containing sodium chloride should be carefully administered to patients with hypertension, heart failure, peripheral or pulmonary oedema, impaired renal function, pre- eclampsia, aldosteronism, or other conditions associated with sodium retention (see also Section 4.5).

Solutions containing potassium salts should be administered with caution to patients with cardiac disease or conditions predisposing to hyperkalemia such as renal or adrenocortical insufficiency, acute dehydration, or extensive tissue destruction as occurs with severe burns.

Although Lactated Ringers Injection has a potassium concentration similar to the concentration in plasma, it is insufficient to produce a useful effect in case of severe potassium insufficiency and therefore it should not be used for this purpose.

Calcium chloride is irritant, therefore care should be taken to prevent extravasation during intravenous injection and intramuscular injection must be avoided. Solutions containing calcium salts should be given cautiously to patients with impaired renal function, or disease associated with elevated vitamin D concentrations such as sarcoidosis. They should be avoided in patients with calcium renal calculi, or a history of renal calculi. In case of concomitant blood transfusion and because of the presence of calcium, Lactated Ringers Injection must not be administered via the same infusion system because of the risk of coagulation.

Lactated Ringers Injection may cause metabolic alkalosis because of the presence of lactate ions.

Lactated Ringers Injection may not produce its alkalinizing action in patients with liver insufficiency since lactate metabolism may be impaired.

The solution containing lactate should be administered with particular care to neonates less than 3 months old.

During long term parenteral treatment, a convenient nutritive supply must be given to the patient.

Interactions Associated with Sodium:

Corticoids/steroids and Carbenoxolone which are associated with the retention of sodium and water (with oedema and hypertension).

Interactions associated with calcium:

Infusion in association with digitalis cardiac glycosides is contra-indicated because of the risk of severe to fatal cardiac arrhythmia particularly in the case of hypokalaemia.

Care should be taken in the concurrent use of thiazide diuretics or vitamin D because of the risk of hypercalcaemia resulting from reduced urinary clearance of calcium.

Bisphosphonates, fluoride, some fluoroquinolones and tetracyclines which are less absorbed (lower availability) when administered with calcium.

Interactions Associated with Potassium:

Care should be taken in concurrent use of drugs containing potassium and drugs which have the potential for inducing hyperkalaemia, such as potassium-sparing diuretics given alone or in combination (such as spironolactone, triamterene, amiloride, potassium canrenoate), Angiotensin Converting Enzyme (ACE) inhibitors, angiotensin-II receptor antagonists,

tacrolimus and ciclosporin.

Interaction associated with lactate (which is metabolized into bicarbonate):

Acidic drugs such as salicylates, barbiturates and lithium whose renal clearance is increased because of the alkalinisation of urine by the bicarbonate resulting from lactate metabolism.

Alkaline drugs, notably sympathomimetic (e.g. ephedrine, pseudoephedrine) and stimulants (e.g. dexamphetamine sulphate, phenfluramine hydrochloride) whose half-life is prolonged (slowest elimination).

The product can be used safely during pregnancy and lactation as long as the electrolyte- and fluid balance is controlled.

It is reminded that calcium crosses the placenta and is distributed into breast milk.

When a medication is added, the nature of the drug and its use during pregnancy and lactation

have to be considered separately.

There is no information of the effects of Lactated Ringers Injection USP on the ability to operate an automobile or other heavy machinery.

During administration of lactated Ringers Injection, the following undesirable effects have been reported as:

Very common:

Allergic reactions or anaphylactic/anaphylactoid symptoms such as localized or generalized

urticaria, skin rash & erythema and itching/pruritus; skin swelling, periobial facial and/or laryngeal oedema (Quincke's oedema).

Nasal congestion, coughing, sneezing, bronchospasm and/or difficulty breathing.

Common:

Chest tightness, chest pain, with tachycardia or bradycardia.

Pruritus has been reported to occur in about 10% of patients receiving the product.

Hyperhydration and heart failure are very common in patients with cardiac disorder or pulmonary oedema.

Electrolytes disturbances have been very commonly reported too.

Lactate infusions commonly induce feelings of anxiety, and a few cases of panic attack have

been reported.

Uncommon:

Seizure may be precipitated by the alkalosis induced by lactate but this is uncommon.

Adverse reactions may be associated with the technique of administration including febrile response, infection at the site of injection, local pain or reaction, vein irritation, venous

thrombosis or phlebitis extending from the site of injection, extravasation, and hypervolemia

Adverse reactions may be associated to the medications added to the solution; the nature of the

additive will determine the likelihood of any other undesirable effects.

In case of undesirable effect(s), the infusion must be discontinued.

Note: To report any side effects please contact;

National Pharmacovigilance and Drug Safety Centre (NPC) Fax: +966-11-205-7662

Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.

Toll free Phone: 8002490000 E-mail: npc.drug@sfda.gov.sa

Website: www.sfda.gov.sa/npc

Overuse or too fast administration may lead to water and sodium overload with a risk of oedema, particularly when there is a defective renal sodium excretion In this case extra renal dialysis may be necessary.

Excessive administration of potassium may lead to the development of hyperkalemia, especially in patients with renal impairment. Symptoms include paresthesia of the extremities, muscle weakness, paralysis, cardiac arrhythmias, heart block, cardiac arrest, and mental confusion.

Excessive administration of calcium salts may lead to hypercalcemia. Symptoms of hypercalcemia may include anorexia, nausea, vomiting, constipation, abdominal pain, muscle weakness, mental disturbances, polydipsia, polyuria, nephrocalcinosis, renal calculi, and, in severe cases, cardiac arrhythmias and coma.

Too rapid intravenous injection of calcium salts may also lead to many of the symptoms of hypercalcemia as well as to chalky taste, hot flushes, and peripheral vasodilatation.

Mild asymptomatic hypercalcemia will usually resolve on stopping administration of calcium and other contributory drugs such as vitamin D. If hypercalcemia is severe, urgent treatment (such as loop diuretics, hemodialysis, calcitonin, bisphosphonates, and trisodium Edetate) is required.

Excessive administration of sodium lactate may lead to hypokalemia and metabolic alkalosis, especially in patients with impaired renal function. Symptoms may include mood changes, tiredness, and shortness of breath, muscle weakness, and irregular heartbeat. Muscle hypertonicity, twitching, and tetany may develop especially in hypocalcemic patients. Treatment of metabolic alkalosis associated with bicarbonate overdose consists mainly of appropriate correction of fluid and electrolyte balance. Replacement of calcium, chloride, and

potassium may be of particular importance.

When overdose is related to medications added to the solution infused, the signs and symptoms of over infusion will be related to the nature of the additive 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 symptomatic and supportive measures should be provided as necessary.

Pharmacotherapeutic group (ATC code): B05BB01 “Electrolytes”.

The solution is an isotonic solution of electrolytes. The constituents of the product and their concentrations are designed to match those of plasma.

The pharmacological properties of the solution are those of its constituents (sodium, potassium, calcium and chloride).

The main effect of the product is the expansion of the extracellular compartment including both the interstitial fluid and the intravascular fluid.

The lactate is metabolized into bicarbonate, mainly in the liver, and produces an alkalinising effect on the plasma.

In healthy volunteers receiving product, central venous pressure changes were associated with a secretion of atrial natriuretic peptide. In healthy volunteers, Lactated Ringers Injection decreased serum osmolality, increased blood pH, and the time until first urination was shorter than that with normal saline.

There is no significant change in glucagon, norepinephrine, epinephrine, blood glucose and insulin levels in aortic surgery patients receiving Lactated Ringers Injection.

When medication is added to Lactated Ringers Injection, the overall pharmacodynamics of the solution will depend on the nature of the drug used.

The pharmacokinetic properties of the product are those of the ions its composition includes (sodium, potassium, calcium and chloride).

Infusion of Lactated Ringers Injection in normal hemodynamically stable adults does not increase circulating lactate concentrations.

The lactate in the solution is metabolized by both oxidation and gluconeogenesis, predominantly in the liver, and bicarbonate is generated by both processes over 1-2 h.

When medication is added to the product, the overall pharmacokinetics of the solution will depend on the nature of the drug used.

Preclinical safety data of Lactated Ringers Injection in animals are not relevant since its constituents are physiological components in animal and human plasma.

Toxic effects are not to be expected under the condition of clinical application.

Ceftriaxone must not be mixed with calcium-containing solutions including Compound Sodium Lactate solution. See also sections 4.3 and 4.4.

As with all parenteral solutions additives may be incompatible. Compatibility of the additives with the Lactated Ringers Injection USP must be assessed before addition. After addition of the additive, incompatibility may become visible by a possible color change and/or the appearance of precipitates, insoluble complex

The Instructions for Use of the medication to be added and other relevant literature must be consulted.

Before adding a substance or medication, verify that it is soluble and/or stable in water and that the pH range of Lactated Ringers Injection USP is appropriate (pH 6.0 to 7.5).

When making additions to Compound Sodium Lactate solution, aseptic technique must be used. Mix the solution thoroughly when additives have been introduced. Do not store solutions containing additives.

As a guidance the following medications are incompatible with the Lactated Ringers Injection USP(non-exhaustive listing):

Aminocaproic acid,

Amphotericin B,

Metaraminol tartrate,

Cefamandole,

Ceftriaxone,

Cortisone acetate,

Diethylstilbestrol,

Etamivan,

Ethyl alcohol,

Phosphate and carbonate solutions,

Oxytetracycline,

Thiopental sodium,

Versenate disodium.

The container is made of Low Density-Polyethylene (LDPE) The primary packaging material Low Density-Polyethylene (LDPE) is used for several years in the pharmaceutical industry for the primary packaging of comparable drug products. The material is known for its

compatibility with the ingredients of the drug product.

The container material, LD (Low Density)-polyethylene meets the requirements of the European Pharmacopoeia (Ph. Eur. 3.2.2).

The material shows a density of 0.9%26-0.9%30 g/cm3.The container can be sterilised at temperatures between 106-112 °C.

Solution containing visible solid particles should not be used.

Do not use unless the solution is clear and the container undamaged.

Do not connect in series and purge the infusion system to remove all air because of the risk of air embolism.

Discard any unused solution.

Verify the integrity of the container and the site for attachment.

For slow infusion only.

Addition of Medicinal Products:

The healthcare professional should assess compatibility by checking absence of colour change or formation of precipitate, insoluble complexes or crystals. Mix thoroughly with the solution.

Use immediately after addition of medicine.