4.1. Therapeutic indications

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

• Supplementation of potassium as a part of parenteral nutrition

4.2. Posology and method of administration

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:

mmol K+required = (BW*[kg] × 0.2)** × 2 × (serum-K+target*** – serum-K+actual [mmol/l])

*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)

Period

Term neonates

Preterm neonates

<1500 g

>1500 g

1st postnatal week

0 – 2.0

1st month of life prior to stable growth

1.0 – 3.0

1.0 – 2.0

1.0 – 3.0

1st month of life with stable growth

1.5 – 3.0

2.0 – 5.0

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.

4.3. Contraindications

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

● Hyperkalaemia,

● Hyperchloraemia,

4.4. Special warnings and precautions for use

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.

4.5. Interaction with other medicinal products and other forms of interaction

● 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.

4.6. Fertility, pregnancy and lactation

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

4.7. Effects on ability to drive and use machines

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

4.8. Undesirable effects

Undesirable effects are listed according to their frequencies as follows:

Very common:

(≥ 1/10)

Common:

(≥ 1/100 to < 1/10)

Uncommon:

(≥ 1/1,000 to < 1/100)

Rare:

(≥ 1/10,000 to < 1/1,000)

Very rare:

(< 1/10,000)

Not known

(Frequency cannot be estimated from the available data)

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.

4.9. Overdose

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.