Ringers solution for infusion indicated to:

Replace extracellular fluid losses - Restore the sodium, potassium, calcium and chloride balances, for treatment of isotonic dehydration.

Adults, older people and children: The dosage depends on the age, weight, clinical and biological conditions of the patient and concomitant therapy. Recommended dosage:

For adults, the elderly and adolescents: 500 ml to 3 liters /24h For babies and children : 20 ml to 100 ml / kg / 24 h.

Administration rate: 
The infusion rate is usually 40 ml/kg/24h in adults, the elderly and adolescents. In paediatric patients the infusion rate is 5 ml/kg/h on average but the value varies with age: 6-8 ml/kg/h for infants, 4-6 ml/kg/h for toddlers, and 2-4 ml/kg/h for schoolchildren. 
In children with burns, the dose is on average 3.4 ml/kg/per cent 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: aged from 28 days to 23 months (a toddler is an infant who can walk) -Children and schoolchildren: aged from 2 years to 11 years.

Method of administration:
 The administration is performed by intravenous route. 
The solution for infusion should be visually inspected prior to use.
 Use only if the solution is clear, without visible particles and if the container is undamaged. 
Administer immediately following the insertion of infusion set. 
Do not remove unit from overwrap until ready for use.
 The inner bag maintains the sterility of the product. Do not use plastic containers in series connections.
 Such use could result in air embolism due to residual air being drawn from the primary container before the administration of the fluid from the secondary container is completed. 
Pressurizing intravenous solutions contained in flexible plastic containers to increase flow rates can result in air embolism if the residual air in the container is not fully evacuated prior to administration.
 Use of a vented intravenous administration set with the vent in the open position could result in air embolism. 
Vented intravenous administration sets with the vent in the open position should not be used with flexible plastic containers. 
The solution should be administered with sterile equipment using an aseptic technique. 
The equipment should be primed with the solution in order to prevent air entering the system. 
Additives may be introduced before infusion or during infusion through the injection site.

Monitoring:
 Fluid balance and plasma electrolyte concentrations (sodium, potassium, calcium and chlorides) must be monitored during administration. Refer to 6.2 (Incompatibilities).

The solution is contraindicated in patients presenting: - Extracellular hyperhydration or hypervolemia - Hypertonic dehydration - Hyperkalaemia - Hypernatraemia - Hypercalcaemia - Hyperchloraemia. - Severe renal insufficiency (with oliguria/anuria). - Uncompensated cardiac failure - Severe hypertension - General oedema and ascitic cirrhosis - Concomitant digitalis therapy (see section 4.5 “Interactions with other medicinal products and other forms of interaction”)

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

Solutions containing sodium chloride should be administered with caution to patients with hypertension, heart failure, peripheral or pulmonary oedema, impaired renal function, pre-eclampsia, aldosteronism or other conditions or treatment (e.g. corticoids/steroids) associated with sodium retention (see also Section 4.5 – Interactions with other medicinal products and other forms of interaction).

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

Because of the presence of calcium;

- Care should be taken to prevent extravasation during intravenous infusion

- The solution should be given cautiously to patients with impaired renal function or diseases associated with elevated vitamin D concentrations such as sarcoidosis.
- In case of concomitant blood transfusion, the solution must not be administered via the same infusion set because of the risk of coagulation.
Ringers Solution for Infusion contains insufficient concentration of potassium and calcium to be used for maintenance of these ions or to correct their deficits. Hence, after dehydration is treated, the IV fluid has to be changed to a maintenance fluid that will provide these ions.
During long-term parenteral treatment, a convenient nutritive supply must be given to the patient.
For information on preparation of the product and additives, please see section 6.6.

 

 

Interaction related to the presence of sodium:
Corticoids/Steroids and carbenoxolone, are associated with the retention of sodium and water (with oedema and hypertension).
Interaction related to the presence of potassium:
- Potassium-sparing diuretics (amiloride, spironolactone, triamterene, alone or in association).
-Angiotensin converting enzyme inhibitors (ACEI) and, by extrapolation, angiotensin II receptor antagonists
- Tacrolimus, cyclosporine
which increase concentration of potassium in the plasma and may lead to potentially fatal hyperkalaemia notably in case of a renal failure increasing the hyperkalaemic effect
Interaction related to the presence of calcium:
- Digitalis glycosides (digitalis cardiotonics) whose effects are enhanced by the presence of calcium and may lead to serious or fatal cardiac arrhythmia
- Thiazide diuretics or vitamin D which can lead to hypercalcaemia when co-administered with calcium.
Interaction with ceftriaxone:
- Concomitant treatment with ceftriaxone and Ringers Solution for Infusion is contraindicated in preterm newborn infants and term newborn infants (≤28 days of age), even if separate infusion lines are used (risk of fatal ceftriaxone-calcium salt precipitation in the neonate’s bloodstream).

Ringers solution for infusion can be used safely during pregnancy and lactation as long as the electrolyte- When a medicinal product is added, the nature of the drug and its use during pregnancy and lactation have to be considered separately.
When a medicinal product is added, the nature of the drug and its use during pregnancy and lactation has to be considered separately.and fluid balance is controlled.

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

During administration of Ringers solution, the adverse reactions have been reported as very common (≥ 10%):
- Hyperhydration and heart failure in patients with cardiac disorder or pulmonary oedema
- Electrolyte disturbances which can cause;
 Difficulty in breathing, sudden severe chest pain.
 Slowing or quickening of your heart beat.
 Too high or low blood pressure.
 Bad fainting attacks, convulsions (fit) or collapse.
 Weakness, lameness, motor disturbances (of muscular movements).
 Numbness, swelling or heaviness of your limbs.
 Cold skin or paleness.
 Difficulty in swallowing.
 Confusion.
 Feeling sick, vomiting.
 Diarrhea or pain in your abdomen.
 Dry mouth or feeling thirsty.
 Sweating or feeling feverish.
 Headaches or dizziness.
 Restlessness.
Adverse reactions may be associated to 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 and extravasation
Adverse reactions may be associated to the medicinal product 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
 

Overdose 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 such cases extra renal dialysis may be necessary Excessive administration of potassium may lead to the development of hyperkalaemia, especially in patients with renal impairment.

Symptoms include paresthesia of the extremities, muscle weakness, paralysis, cardiac arrhythmias, heart block, cardiac arrest, and mental confusion. Treatment of hyperkalaemia involves the administration of calcium, insulin (with glucose), sodium bicarbonate, exchange resins or dialysis.

Excessive administration of calcium salts may lead to hypercalaemia. Symptoms of hypercalaemia 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 hypercalaemia as well as to a chalky taste, hot flushes, and peripheral vasodilatation. Mild asymptomatic hypercalaemia will usually resolve on stopping administration of calcium and other contributory drugs such as vitamin D.

If hypercalaemia is severe, urgent treatment (such as loop diuretics, haemodialysis, calcitonin, bisphosphonates, trisodium edetate) is required.
Excessive administration of chloride salts may cause a loss of bicarbonate with an acidifying effect.

When overdose is related to medicinal products 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: “Electrolytes”, ATC code: B05BB01.
Ringers solution for infusion is an isotonic solution of electrolytes. The constituents of Ringers solution for infusion and their concentrations are designed to match those of plasma.
The pharmacodynamics properties of this solution are those of its components (water, sodium, potassium, calcium, and chloride).

The main effect of Ringers Solution for Infusion is the expansion of the extracellular compartment including both the interstitial and intravascular fluids.
Ions, such as sodium, circulate through the cell membrane using various mechanisms of transport among which is the sodium pump (Na-K-ATPase). Sodium plays an important role in neurotransmission and cardiac electrophysiology, and also in its renal metabolism.
Potassium is essential for numerous metabolic and physiological processes including nerve conduction, muscle contraction, and acid-base regulation.

A normal concentration of potassium in plasma is about 3.5 to 5.0 mmoles per liter. Potassium is predominantly an intracellular cation, primarily found in muscle; only about 2% is present in the extracellular fluid.

The passage of potassium into the cells and retention against the concentration gradient requires active transport via the Na+/K+ ATPase enzyme.
Approximately 99% of calcium is incorporated into the skeleton.

The remaining 1% is found in body tissues and fluids, and is essential for normal nerve conduction, muscle activity, and blood coagulation.
Chloride is mainly an extracellular anion found in low concentration in bone and in high concentration in some components of connective tissue such as collagen.

Intracellular chloride is in high concentration in red blood cells and gastric mucosa.

The balance of anions and cations are regulated by the kidneys. Reabsorption of chloride generally follows reabsorption of sodium.

The pharmacokinetic properties of this solution are those of its components (sodium chloride, potassium chloride, and calcium chloride).
The volume and the ionic composition of the extracellular and the intracellular compartments are as follows:

Extracellular fluid:                               approximately 19 liters

Sodium (mmol/l):                                 142

 Potassium (mmol/l):                           5  

 Calcium (mmol/l)                                2.5 

Chloride (mmol/l):                              103

Intracellular fluid:                              approximately 23 liters

Sodium (mmol/l):                               15

Potassium (mmol/l):                         150

Calcium (mmol/l):                               1

Chloride (mmol/l):                              1

After injection of radiosodium (24 Na), the half-life is 11 to 13 days for 99% of the injected Na and one year for the remaining 1%.

The distribution varies according to tissues: it is fast in muscles, liver, kidney, cartilage and skin; it is slow in erythrocytes and neurons; it is very slow in the bone. Sodium is predominantly excreted by the kidney, but there is extensive renal reabsorption.

Small amounts of sodium are lost in the faeces and sweat. Factors influencing potassium transfer between intracellular and extracellular fluid such as acid-base disturbances can distort the relationship between plasma concentrations and total body stores.

Potassium is excreted mainly by the kidneys; it is secreted in the distal tubules in exchange of sodium or hydrogen ions.

The capacity of the kidneys to conserve potassium is poor and some urinary excretion of potassium continues even when there is severe depletion.

Some potassium is excreted in the faeces and small amounts may also be excreted in sweat.

The concentration of calcium in plasma is regulated by parathyroid hormone, calcitonin, and vitamin D. About 47% of calcium in plasma is in the ionised physiologically active form, about 6% is complexed with anions such as phosphate or citrate, and the remainder is bound to proteins, principally albumin. If the plasma-albumin concentration is raised (as in dehydration) or reduced (as is common in malignancy) it will affect the proportion of ionized calcium. Thus, the total plasma-calcium concentration is commonly adjusted for plasma albumin. Excess of calcium is predominantly excreted renally. Unabsorbed calcium is eliminated in the faeces, together with that secreted in the bile and pancreatic juice. Minor amounts are lost in the sweat, skin, hair, and nails. Calcium crosses the placenta and is distributed into breast milk.

Preclinical safety data of Ringers solution for infusion in animals are not relevant since its constituents are physiological components of animal and human plasma. Toxic effects are not to be expected under the condition of clinical application. The safety of potential additives should be considered separately

Water for Injections.

Incompatibility of the medicinal product to be added with the solution in container must be assessed before addition.

In the absence of compatibility studies, this solution must not be mixed with other medicinal products.

The Instructions for Use of the medicinal product to be added must be consulted. Before adding a drug, verify it is soluble and stable in water at the pH of Ringers Solution for Infusion (see section 3).

Calcium salts have been reported to be incompatible with a wide range of drugs.

Complexes may form resulting in the formation of a precipitate.
As a guidance, the following medications are incompatible with the Ringers Solution (non-exhaustive listing):

− Amphotericin B

− Cortisone

− Erythromycin lactobionate

− Etamivan

− Ethyl alcohol

− Thiopental sodium

− Disodium edetate

Those additives known to be incompatible should not be used.
 

36 Months

Do not store above 30°C.

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.

For single use only. Do not use unless the solution is clear and the container undamaged. Discard any unused solution.
Any unused product or waste material should be disposed of in accordance with local requirements.
Addition of medicinal products:
Confirm additive compatibility before use.
Clean the injection site using antiseptic solution.
Carefully introduce the sterile needle into the sterile chamber in the injection site, attach the needle to the container with the medicinal product, introduce the needle through the second membrane into the bag and inject the medicine. Carefully withdraw the needle.
Mix thoroughly with the solution. Use immediately.