Sterile Potassium Chloride concentrate (15 % w/v) BP

• Treatment of potassium deficiency, in particular if accompanied by hypochloraemic alkalosis.

• Supplementation of potassium as a part of parenteral nutrition

Posology

The dosage should be adjusted according to the actual serum electrolyte concentrations and the acid base status and the individual requirements of the patient. Potassium concentrates for infusion must be diluted with a compatible i.v. solution prior to administration.

Adults and elderly patients

Treatment of moderate, asymptomatic potassium deficiency:

The amount required for correction of moderate potassium deficiency and in maintenance may be calculated according to the following formula:

*BW = body weight

^**Term represents the extracellular fluid volume

^***K⁺_target should be 4.5 mmol per litre

Maximum infusion rate

Up to 10 mmol potassium per hour (corresponding to 0.15 mmol potassium/kg body weight per hour).

Treatment of severe symptomatic potassium deficiency (serum potassium level below 2.5 mmol per litre):

Maximum daily dose

Up to 2 – 3 mmol/kg body weight/day

Maximum infusion rate

Up to 20 mmol potassium per hour (corresponding to 0.3 mmol potassium/kg body weight per hour).

If serum potassium levels are below 2 mmol per litre and continuous ECG monitoring is ensured, the infusion rate may be as high as 40 mmol per hour.

Potassium supplementation as part of parenteral nutrition:

The daily requirements of potassium are 1- 1.5 mmol/ kg body weight.

The administration rate should not exceed 10 mmol potassium per hour (corresponding to 0.15 mmol potassium/ kg body weight per hour)

Paediatric population

Treatment of potassium deficiency

In children, the solution must be diluted to a concentration of 20-40 mmol of KCl per litre before administration.

Maximum daily dose

The maximum daily dose depends on the severity of potassium deficiency and overall condition of the individual patient. The maximum daily dose might therefore exceed the amount of potassium given as part of parenteral nutrition (see section “Potassium supplementation as part of parenteral nutrition” below).

Maximum infusion rate

Symptomatic hypokalemia can be corrected at a maximal rate of 1 mmol/kg body weight per hour with a maximum rate of 20 mmol/h.

Potassium supplementation as part of parenteral nutrition:

Recommended maximum daily dose for potassium supplementation as part of parenteral nutrition (in mmol/kg body weight)

Children and infants after the first month of life must not receive more than 3 mmol per kg body weight per day.

Other special patient groups

Changes in acid-base balance affect plasma concentrations. The demand of potassium is increased in compensation of ketoacidosis in diabetic patients and when glucose/insulin is given.

Method of administration

Intravenous use (see section 4.4).

Only to be administered by infusion after dilution in suitable infusion solutions.

The potassium concentration in the infusion solution should normally not exceed 40 mmol per litre.

If serum potassium levels in adults are below 2 mmol per litre the potassium concentration in the infusion solution may be as high as 80 mmol per litre.

For instructions on dilution of the medicinal product before administration, see section 4.4 and 6.6.

As a matter of principle, infusion pumps should be used for the infusion of potassium in the setting of correction therapy.

Sterile Potassium Chloride Concentrate (15% w/v) BP must not be administered in case of:

● Hyperkalaemia,

● Hyperchloraemia,

Sterile Potassium Chloride Concentrate (15% w/v) BP should only be administered with caution in the presence of:

● Cardiac disease

● Disorders associated with potassium retention such as impaired renal function, Addison's disease, sickle cell anaemia. Treatment of patients with severe renal impairment and patients on dialysis must be consulted with nephrologist.

● Concurrent treatment with potassium-saving diuretics, Angiotensin II receptor antagonists, ACE inhibitors or potentially nephrotoxic medicinal products (nonsteroidal anti-inflammatories etc.), see also section 4.5.

● Shock

● Extensive tissue destruction (e.g. burn injuries)

● Hyperkalaemic familial periodic paralysis

Sudden discontinuation of potassium administration may be followed by marked hypokalaemia, which may lead to increased toxicity of cardiac glycosides taken concomitantly.

Initial potassium replacement therapy must not include glucose infusions, because glucose may cause a further decrease in the plasma-potassium concentration.

ECG monitoring should be available.

There are typical changes in the ECG when the potassium balance is disturbed (hypo- or hyperkalaemia). However, there is no linear relationship between the ECG changes and the concentration of potassium in the blood.

Refeeding syndrome

Refeeding severely undernourished patients may result in the refeeding syndrome. Refeeding syndrome consists of hypophosphatemia which is often accompanied by hypokalaemia, hypomagnesaemia, fluid retention and hyperglycaemia. Thiamine deficiency and fluid retention may also develop. Careful monitoring and slowly increasing nutrient intakes while avoiding overfeeding can prevent these complications.

Clinical monitoring should include checks of the serum electrolyte levels and the acid-base balance.

It must be made absolutely sure that the solution is administered intravenously, because paravenous administration may cause tissue necrosis.

As a matter of principle, infusion pumps should be used for the infusion of potassium in the setting of correction therapy.

Elderly patients:

Elderly patients, who are more likely to suffer from cardiac insufficiency and renal impairment, should be closely monitored during treatment, and the dosage should be carefully adjusted.

● Cardiac glycosides

An increase in the extracellular potassium concentration reduces the effect of cardiac glycosides, a decrease leads to an intensification of the arrythmogenic effect of cardiac glycosides.

● Medicinal products reducing potassium excretion

These include:

- potassium saving diuretics (e.g. triamterene, amiloride, spironolactone)

- Angiotensin II receptor antagonists

- ACE inhibitors

- tacrolimus

- ciclosporin

- non-steroidal anti-inflammatory drugs

- peripheral analgesics

- heparin

Severe hyperkalaemia, adversely affecting heart rhythm, can result when these drugs are administered concurrently with potassium chloride.

• Medicinal products increasing potassium excretion

ACTH, corticosteroids and loop diuretics can increase the renal elimination of potassium.

● Suxamethonium

Severe hyperkalaemia, with adverse effect on the heart rhythm, can also occur when suxamethonuium and potassium are administered concurrently.

Pregnancy

There are no or limited amount of data from the use of Potassium Chloride Concentrates in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3).

On the basis of known physiological effects of potassium, no adverse effects on the unborn are expected of a normalization of an abnormal serum potassium concentration. Too high or too low potassium levels can however be detrimental to maternal and fetal cardiac function.

The product should be used only when clearly needed and after careful weighing out expected benefits against possible risks.

Lactation

Potassium Chloride is excreted in human milk. However, from a normalization of potassium in the blood no adverse effect is expected on the potassium level in breast milk. Potassium chloride concentrate for infusion - if used according to the directions given - may therefore be used during lactation.

Fertility

No data available

Sterile Potassium Chloride Concentrate (15 % w/v) BP has no or negligible influence on the ability to drive and use machines.

Undesirable effects are listed according to their frequencies as follows:

Metabolism and nutrition disorders

Not known: Acidosis, hyperchloraemia

Cardiac disorders

Not known: Too rapid infusion may provoke cardiac arrhythmia.

Gastrointestinal disorders

Not known: Nausea

General disorders and administration site conditions

Not known: Local reactions at the site of administration, including local pain, vein irritation, thrombophlebitis and extravasation

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.

Symptoms

Overdose may cause hyperkalaemia, in particular in the presence of acidosis or kidney insufficiency.

The symptoms of hyperkalaemia are primarily cardiovascular disorders. They may include bradycardia, AV blockade, ventricular fibrillation and cardiac arrest. In the ECG there are high, sharp, symmetrical T-waves and, at very high potassium levels, broadening of the QRS complex. The vascular effects are hypotension and centralisation.

The neuromuscular symptoms include fatigue, weakness, states of confusion, heaviness of limbs, muscle twitching, paraesthesia, and ascending paralysis.

Plasma potassium concentrations of 6.5 mmol/l or more are dangerous, over 8 mmol/l often lethal.

Treatment

The first measure is immediate stop of infusion.

Further corrective measures include slow intravenous administration of 10 % calcium gluconate, infusion of glucose together with insulin, increase of diuresis, oral or rectal administration of cation exchangers, correction of acidosis, if necessary.

In severe cases haemodialysis may be necessary.

Pharmacotherapeutic group: IV solution additives - electrolytes

ATC code: B05X A01

Mechanism of action

Potassium is the most important cation of the intracellular space, approx. 98 per cent of the organism's total potassium is located there.

Potassium is involved in electrochemical processes of cells and in carbohydrate and protein metabolism.

Potassium deficiency may be caused by increased renal excretion, increased gastro-intestinal losses, e.g. by vomiting or diarrhoea, or through fistulae, by increased intracellular uptake, e.g. during therapy of acidosis or therapy with glucose and insulin, or by insufficient potassium intake.

Hypokalaemia is accompanied by muscle weakness, atony of gastro-intestinal smooth muscles (constipation up to paralytic ileus), loss of capability of kidneys to concentrate urine, ECG alterations and cardiac arrhythmia.

Absorption

As the medicinal product is administered intravenously, its bioavailability is 100 per cent.

Distribution

The distribution of potassium follows the normal physiological pathways of potassium metabolism.

The plasma potassium concentration is closely related to the acid-base balance. Alkalosis is often accompanied by hypokalaemia and acidosis by hyperkalaemia. Normal plasma potassium concentrations in acidosis indicate potassium deficiency.

The intracellular potassium concentration is approx. 140-150 mmol/l. The normal potassium serum concentration is between 3.5 and 5 mmol/l.

Elimination

Potassium is mainly excreted into the urine (about 90 per cent) and about 10 per cent are excreted via the gastro-intestinal tract.

Non-clinical data are insufficient. If electrolytes are kept within physiological range, toxic effects are not expected.

Water for injections

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

Unopened

30 months

After first opening the container

To be added to diluent immediately after opening the container. See also section 6.6.

After dilution

From a microbiological point of view, dilutions should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8 ° C, unless dilution has taken place in controlled and validated aseptic conditions.

Chemical and physical in-use stability has been demonstrated for 24 hours at 20°C with the products identified in section 6.6.

Do not store above 25 °C

For storage conditions of the diluted product see section 6.3.

The medicinal product is supplied in

● polyethylene (LDPE) plastic ampoules containing 10 ml

supplied in packs of 20 x 10 ml

No special requirements for disposal.

Containers are for single-use only. Containers once opened must be discarded after use.

Do not use if solution is not clear or the container or closure show visible signs of damage.

Sterile Potassium Chloride Concentrate (15 % w/v) BP may be diluted in e.g.:

● 5 % or 10 % glucose solutions

● 0.9% sodium chloride solution

● Compound Sodium Lactate solution

Sterile Potassium Chloride Concentrate (15 % w/v) BP should only be added immediately before setting up the infusion and strictly aseptic technique should be observed. The infusion container should then be gently shaken.