Half Strength Darrows 5 %/000 ml Solution

Fluid and/or electrolyte deficiency states where dextrose supplementation is required.

Posology

Adults

In adults somewhat less than the average daily maintenance dose of potassium is supplied in one litre. In potassium deficiency 70 u2013 80 mmol of potassium (or more) should be given daily. Intravenously the maximum rate is 3 ml per minute for adults. It is desirable not to give more than 10 mmol of potassium per hour to adults if large amounts are indicated and correspondingly less to infants and children.

Special populations

Paediatric population

After adequate hydration and renal function are assumed by means of the initial hydrating solution, the dose is usually 80 ml per kilogram of body weight for the first 24 hours. After the first day, 22 u2013 53 ml per kilogram of body weight per day may be given as long as the stools remain watery. Additional fluid required daily may be provided by carbohydrate in water in amounts calculated so that the total fluid (with and without potassium) will be 150 u2013 200 ml per kilogram of body weight.

Method of administration

For IV use. Fluid balance, serum glucose, serum sodium and other electrolytes may need to be monitored before and during administration, especially in patients with increased non-osmotic vasopressin release (syndrome of inappropriate antidiuretic hormone secretion, SIADH) and in patients co-medicated with vasopressin agonist medicines due to the risk of hyponatraemia. Monitoring of serum sodium is particularly important for physiologically hypotonic fluids. HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS may become extremely hypotonic after administration due to glucose metabolisation in the body (see sections 4.4, 4.5 and 4.8). HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS may cause venous irritation and phlebitis. Therefore, it is recommended that HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS be administered through a large central vein, for thorough and rapid dilution of the hyperosmolar solution. HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS should be inspected visually for particulate matter and discolouration prior to administration, whenever the solution and container permit (see section 4.4). Do not administer unless the solution is clear, and seal is intact. Only sterile and nonpyrogenic equipment must be used for intravenous administration. The equipment should be primed with the solution to prevent air embolism due to residual air in the system. Additives may be introduced before infusion or during infusion through the injection site. Additives may be incompatible. Check additive compatibility with both the solution and container prior to use. Complete information is not available. Those additives known to be incompatible should not be used.

A gradual increase of flow rate should be considered when starting administration of glucose-containing products, as in HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS. If in the informed judgment of the medical practitioner, it is deemed advisable to introduce additives, use aseptic technique. Mix thoroughly and carefully when additives have been introduced. Do not store the solution containing additives.

• Hypersensitivity to any active ingredient, maize (maize is the raw material used in the production of dextrose), or to any ingredient of HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS (see section 6.1).
• Renal insufficiency.
• Crush syndrome.
• Severe haemolytic reactions.
• Adrenocortical insufficiency.
• Hyperkalaemia.
• Early postoperative oliguria, except when gastrointestinal drainage is being done.
• Hypernatraemia.
• Hyperchloraemia.
• Uncompensated cardiac failure.
• Uncompensated diabetes, other known glucose intolerances (such as metabolic stress situations), hyperosmolar coma, hyperglycaemia and hyperlactataemia.

Glucose intravenous infusions are usually isotonic solutions. In the body, however, glucose-containing fluids can become extremely physiologically hypotonic due to rapid glucose metabolisation (see section 4.2).

Depending on the tonicity of the solution, the volume and rate of infusion and depending on a patient's underlying clinical condition and capability to metabolise glucose, intravenous administration of glucose can cause electrolyte disturbances, most importantly hypo- or hyperosmotic hyponatraemia.

Hypersensitivity reactions

Hypersensitivity/infusion reactions, including anaphylaxis, have been reported (see section 4.8). Stop the infusion immediately if signs or symptoms of hypersensitivity/infusion reactions develop. Appropriate therapeutic countermeasures must be instituted as clinically indicated.

Risk of hyperkalaemia

Hyperkalaemia is the most frequently occurring and serious hazard of potassium treatments. Since an exact measurement of potassium deficiency is not usually possible, potassium supplement should be administered slowly and with caution. HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS should be administered with caution to patients with conditions predisposing to hyperkalaemia and/or associated with increased sensitivity to potassium, such as patients with potassium-aggravated skeletal muscle channelopathies (e.g. hyperkalaemic periodical paralysis, congenital paramyotonia, and potassium-aggravated myotonia/patamyotonia).

HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS should be used with great care, if at all, in patients with cardiac disease including congestive heart failure or AV block (especially if they receive digitalis), conditions predisposing to hyperkalaemia such as renal or adrenocortical insufficiency, acute dehydration or extensive tissue destruction as occurs with severe burns.

HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS should be administered with considerable care to patients with hypertension, heart failure, peripheral or pulmonary oedema, impaired renal function, pre-eclampsia or clinical states in which there exist oedema with sodium retention.

The administration of HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS can cause fluid and/or solute overloading resulting in dilution of the serum electrolyte concentrations, overhydration, congested states, or pulmonary oedema. The risk of dilution states is inversely proportional to the electrolyte concentrations of the infusions. The risk of solute overload causing congested states with peripheral and pulmonary oedema is directly proportional to the electrolyte concentrations of the infusions.

Use in patients with or at risk of alkalosis

HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS should be administered with particular caution, if at all, to patients with alkalosis or at risk of alkalosis, because lactate is metabolised to bicarbonate and administration may result in, or worsen, metabolic alkalosis. The effect of the sodium lactate component in HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS on patients with metabolic or respiratory alkalosis should be monitored closely.

Use in patients with or at risk for increased lactate levels or with impaired lactate utilisation

HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS should be administered with extreme caution, if at all, to patients with conditions associated with increased lactate levels, impaired lactate utilisation such as cardiac disease, shock and severe hepatic insufficiency or otherwise at risk of alkalosis. Hyperlactataemia (i.e. high lactate levels) can develop in patients with severe hepatic insufficiency, since lactate metabolism may be impaired. In addition, HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS may not produce its alkalinising action in patients with severe hepatic insufficiency, since lactate metabolism may be impaired. Less frequently seizures may be precipitated by the alkalosis induced by lactate.

Lactate-containing solutions should be administered with particular caution to neonates and infants less than 6 months of age (see also u201cPaediatric patientsu201d). HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS should be used with care in patients with subclinical diabetes mellitus (see section 4.5), hyperkalaemia, severe renal failure, and in conditions in which potassium retention is present. Careful monitoring of plasma levels is recommended in these clinical situations.

Administration of HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS may lead to hyperglycaemia, therefore it is not recommended to use this solution after acute ischaemic strokes, as hyperglycaemia has been implicated in increasing cerebral ischaemic brain damage and impairing recovery. If hyperglycaemia occurs, rate of infusion should be adjusted, or insulin administered (see section 4.5).

HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS should be administered with caution to patients who are at risk of experiencing hyperosmolarity, acidosis or undergoing correction of alkalosis (conditions associated with a shift of potassium from intracellular to extracellular space) and patients treated concurrently or recently with medicine that can cause hyperkalaemia. HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS should be used with caution in patients with cardiac dysrhythmia. Dysrhythmias can develop at any time during hyperkalaemia. Frequently, mild or moderate hyperkalaemia is asymptomatic and may be manifested only by increased serum potassium concentrations, and possibly characteristic electrocardiogram (ECG) changes.

Hyponatraemia

HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS should be used with particular caution in patients with or at risk of hyponatraemia. Glucose intravenous infusions, such as HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS, are usually isotonic solutions. In the body, however, glucose-containing fluids can become extremely physiologically hypotonic due to rapid glucose metabolisation. Monitoring of serum sodium is particularly important for hypotonic fluids. Depending on the tonicity of the solution, the volume and rate of infusion, and depending on a patientu2019s underlying clinical condition and capability to metabolise glucose, intravenous administration of glucose can cause electrolyte disturbances, most importantly hypo- or hyperosmotic hyponatraemia. Patients with non-osmotic vasopressin release (e.g. in acute illness, pain, postoperative stress, infections, burns and central nervous system (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 (brain oedema) characterised by headache, nausea, seizures, lethargy and vomiting. Patients with brain oedema are at particular risk of severe, irreversible and life-threatening brain injury. Acute symptomatic hyponatraemic encephalopathy is considered a medical emergency. Children, women of childbearing potential and patients with reduced cerebral compliance (e.g. meningitis, intracranial bleeding and cerebral contusion) are at particular risk of the severe and life-threatening brain swelling caused by acute hyponatraemia.

Medicines leading to an increased vasopressin effect

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

• Medicines stimulating vasopressin release, e.g. chlorpropamide, clofibrate, carbamazepine, vincristine, selective serotonin reuptake inhibitors, 3,4-methylenedioxy-N-methamphetamine, ifosfamide, antipsychotics, narcotics.
• Medicines potentiating vasopressin action, e.g. chlorpropamide, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclophosphamide.
• Vasopressin analogues, e.g. desmopressin, oxytocin, vasopressin, terlipressin.

Medicine increasing the risk of hyponatraemia

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

Blood

HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS should not be administered simultaneously with blood through the same administration set because of the possibility of haemolysis and pseudo-agglutination.

Medicines or products causing hyperkalaemia or increasing the risk of hyperkalaemia

Use with caution in patients treated with medicines or products that can cause hyperkalaemia or increase the risk of hyperkalaemia, e.g. potassium-sparing diuretics (such as amiloride, spironolactone, triamterene), angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists. The simultaneous administration of these medicines can result in increased risk of severe and potentially fatal hyperkalaemia, in particular in the presence of other risk factors for hyperkalaemia. HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS should also be used with caution concomitantly with ciclosporin, tacrolimus and medicines that contain potassium.

Medicine affecting glycaemic control

Concurrent use of HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS with insulin will decrease serum potassium. Use of HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS may necessitate review of a patientu2019s oral hypoglycaemic or insulin requirements, so close monitoring of serum glucose levels is also required. Both the glycaemic effects of HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS and its effects on water and electrolyte balance should be taken into account when using these products in patients treated with other medicines that affect glycaemic control, or fluid and/or electrolyte balance.

The safety of HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS in pregnancy and lactation has not been established. HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS should be administrated with special caution to pregnant woman during labour, particularly if administered in combination with oxytocin, due to the risk of hyponatraemia (see sections 4.4, 4.5 and 4.8).

None known.

Immune system disorders

Frequency not known: anaphylactic reactions, hypersensitivity, pyrexia and chills

Metabolism and nutrition disorders

Frequency not known: hospital-acquired hyponatraemia**, hyperkalaemia, hyperchloraemic acidosis

Nervous system disorders

Frequency not known: hyponatraemic encephalopathy**

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

Cardiac disorders

Frequency not known: cardiac arrest

General disorders and administrative site conditions

Frequency not known: fluid and electrolyte disturbances.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS is important. It allows continued monitoring of the benefit/risk balance of HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS. Health care providers are asked to report any suspected adverse reactions via the u201cAdverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8. Health care providers are asked to report any suspected adverse drug reactions to the Holder of the Certificate of Registration at the following email address: [email protected] and to the relevant medicineu2019s regulatory authority in the country where the product is marketed.

Symptoms

There is no overdose experience with HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS IV infusion preparations. However, an excessive volume or too high a rate of administration may lead to fluid and sodium overload with a risk of oedema (peripheral and/or pulmonary), particularly when renal sodium excretion is impaired. Excessive administration of lactate may lead to metabolic alkalosis, which may be accompanied by hypokalaemia. Excessive administration or impaired excretion of potassium may lead to:

• hyperglycaemia, adverse effects on water and electrolyte balance, and corresponding complications (e.g. severe hyperglycaemia and severe dilutional hyponatraemia and their complications, can be fatal)
• hyponatraemia (which can lead to CNS manifestations including seizures, coma, cerebral oedema and death)
• hypernatraemia, especially in patients with severe renal impairment
• fluid overload (which can lead to central and/or peripheral oedema)
• development of potentially fatal hyperkalaemia (see section 4.8). If hyperkalaemia is present or suspected, discontinue the infusion immediately and institute close ECG, laboratory and other monitoring and, as necessary, corrective therapy to reduce serum potassium levels. Manifestations of hyperkalaemia may include:

- disturbances in cardiac conduction and dysrhythmias, including bradycardia, heart block, asystole, ventricular tachycardia, ventricular fibrillation

- hypotension

- muscle weakness up to and including muscular and respiratory paralysis, paresthesia of extremities

- gastrointestinal symptoms (ileus, nausea, vomiting, abdominal pain).

- dysrhythmias and conduction disorders, in addition to dysrhythmias and conduction disorders, the ECG shows progressive changes that occur with increasing potassium levels. Possible changes include:

• peaking of T waves
• loss of P waves
• QRS widening.

However, the correlation between potassium levels and ECG changes is not precise, and whether or at which potassium level certain ECG signs develop depends on factors such as patient sensitivity, the presence of other electrolytes disorders, and the rapidity of the development of hyperkalaemia. The presence of any ECG findings that are suspected to be caused by hyperkalaemia should be considered a medical emergency. When assessing an overdose, any additives in the solution must also be considered. Clinically significant overdose of HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS may, therefore, constitute a medical emergency. Overdose is usually asymptomatic and may only be manifested by increased serum potassium levels and characteristic ECG features (see sections 4.4 and 4.8).

Treatment

No specific antidotes to this preparation are known, interventions include discontinuation of HALF STRENGTH DARROWS SOLUTION WITH 5 % DEXTROSE FRESENIUS administration, dose reduction, administration of insulin and other measures as indicated for the specific clinical constellation. Should overdose occur, treatment should be discontinued and the patient should be observed for symptoms of the infusion, including any additives, with appropriate supportive measures instituted as required. The use of potassium-containing foods or medicine causing potassium retention must also be discontinued. Treatment of hyperkalaemia depends on its severity. If hyperkalaemia is present or suspected, discontinue the infusion immediately and institute close ECG, laboratory and other monitoring and, as necessary, corrective therapy to reduce serum potassium levels. It must be kept in mind that rapid lowering of serum potassium concentrations in digitalised patients can cause cardiac toxicity. Clinically, only the intravascular potassium concentration causes cardiac disorders. Therefore, infusion of the potassium chloride solution and other exogenous sources of potassium, such as potassium-rich containing foods or medicine causing potassium retention (potassium-sparing diuretic) must be discontinued immediately. In patients with severe hyperkalaemia, measures, which facilitate the shift of potassium ions from the vascular to the intracellular space, should be initiated. It can be achieved by administration of sodium bicarbonate, glucose/insulin, or calcium gluconate infusions. In patients with serum potassium concentrations greater than 6,5 mmol/l, intravenous infusion of 40 u2013 160 mmolar of sodium bicarbonate over a 5-minute period has been recommended. This dose may be repeated every 15 minutes if ECG abnormalities persist. This treatment results in a temporary alkalosis and lowers serum potassium levels by 0,6 mmol/l for every 0,1 increase of the pH.

Glucose/insulin infusion is another treatment for an overdose episode with potassium chloride medicine. It consists of 300 u2013 500 ml of 10 u2013 25 % glucose intravenous infusion containing 5 u2013 10 IU insulin per 20 g of glucose infused over a 1-hour period. Patients whose ECGs show the absence of P waves or a broad QRS complex and who are not receiving cardiac glucosides should immediately be given intravenously 0,5 u2013 1,0 g (5 u2013 10 ml of a 10 % solution) of calcium gluconate or another calcium salt over a 2-minute period (with continuous ECG monitoring) to antagonise the cardiac toxic effects of potassium. If ECG abnormalities persist, repeated doses of calcium salt may be given, allowing 1 u2013 2 minutes between doses. When the ECG approaches normal, efforts should be directed toward removal of excess potassium from the body. This is a choice of treatment, when the removal of the potassium should be initiated as soon as possible. This is accomplished by administration of sodium polystyrene sulphonate resin orally or rectally, where sodium is exchanged with potassium in the gastrointestinal tract. One gram of resin will remove 1 mmol of potassium, but at the same time it will add 2 u2013 3 mmol of sodium, which may lead to a sodium overload. To overcome the constipating effect of the resin, it is formulated in sorbitol solution (20 %). The initial dose of 30 u2013 60 g of resin in 120 u2013 240 ml of 20 % sorbitol has been recommended. It can be repeated every 1 u2013 2 hours. As a last resort, haemodialysis or peritoneal dialysis can be used to remove potassium from the body, in particular, in patients with renal impairment. The infusion of furosemide (high dose diuretics) with a substantial amount of sodium chloride and bland solution will excrete potassium at the distal tubules of the renal system by sodium exchange mechanism into the urine.