POTASSIUM CHLORIDE KABI 0.04 mEq/mL in 3.3% GLUCOSE and 0.3% SODIUM CHLORIDE PERFUSION SOLUTION

2. What you need to know before you use Potassium Chloride Kabi 0.04 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for Infusion

Do not use Potassium Chloride Kabi 0.04 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for Infusion

• if you are allergic to potassium chloride, glucose or sodium chloride or any of the other components of this medicine (listed in section 6)
• if your blood potassium levels are high (hyperkalemia)
• if you have severe kidney disease with oliguria (reduced urine excretion), anuria (absence of urine production) or azotemia (presence of excess nitrogen waste in the blood due to kidney failure)
• if your blood chloride levels are high (hyperchloremia)
• if your blood sodium levels are high (hypernatremia)
• if you suffer from states of hyperhydration (excess water in the body)
• if you suffer from states of hyperglycemia (high blood glucose levels) such as in cases of hyperosmolar coma, uncontrolled diabetes or other glucose intolerance as in situations of metabolic stress.
• if you suffer from renal tubular acidosis (kidney function disorder)
• if you have had an acute ischemic stroke (sudden loss of brain function due to a blockage in blood flow)
• within the first 24 hours after a head injury.

Warnings and Precautions

Consult your doctor or nurse before starting to use Potassium Chloride Kabi 0.04 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for Infusion.

Potassium administration should always be carried out under strict medical supervision. During the administration of this medicine, and in order to detect early signs of excessive potassium levels (hyperkalemia), your doctor will monitor your heart with electrocardiograms and perform periodic blood tests to determine potassium levels in the blood, especially:

• if you have any heart or kidney disease, or other situations that favor the appearance of hyperkalemia.
• if you are taking other medicines that may increase potassium levels in the blood (see the following subsection).

Your doctor should exercise extreme caution if you are receiving digitalis, especially when stopping potassium administration, since a rapid decrease in potassium levels can cause digitalis toxicity. In these cases, potassium treatment should not be stopped abruptly.

Potassium solution should only be administered if you have adequate urine flow. If not, you may need to be given a solution that does not contain potassium.

Your doctor will perform frequent medical and laboratory tests to monitor changes in fluid and acid-base balance and electrolyte and glucose levels in the blood

If you are in an emergency situation and your blood potassium levels are very low or if you are taking digitalis medicines, it is not recommended to administer glucose solutions since the presence of glucose prevents potassium levels from increasing as quickly as they should.

If you suffer from episodes of intracranial hypertension, your doctor will closely monitor your blood glucose levels.

Since this medicine contains glucose, it should be administered with caution if you have a vitamin B1 deficiency or diabetes. Your doctor may give you this medicine as long as you have previously received adequate treatment

Since this medicine contains sodium, it should be administered with caution if you have hypertension, congestive heart failure, pulmonary or peripheral edema, renal failure, preeclampsia (development of hypertension during pregnancy) or other conditions associated with sodium retention, as well as if you are taking corticosteroids or corticotropin (see the following subsection).

This medicine should be administered with special caution if you are elderly, as you may be taking other medicines (see the following subsection) or your kidneys or heart may not be functioning correctly, or you may have other diseases that can affect potassium levels in the blood.

If administration is prolonged, extravasation (leakage of the solution from the vein into the surrounding tissue) or thrombophlebitis (inflammation of the vein associated with clot formation) may occur

Be especially careful with Potassium Chloride Kabi 0.04 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for Infusion:

• If you suffer from critical states, pain, postoperative stress, infections, burns or central nervous system diseases.
• You have any type of heart, liver, or kidney disease and are being treated with a medicine that increases the effect of vasopressin (a hormone that regulates the body's water retention) because it may increase the risk of acquiring low sodium levels in the blood (hyponatremia) in the hospital. (See the section on the use of Potassium Chloride Kabi 0.04 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for Infusion with other medicines).

All patients should be closely monitored. In cases where normal regulation of blood water content is altered due to increased vasopressin secretion, also known as Antidiuretic Hormone (ADH), perfusion of fluids with low sodium chloride concentration (hypotonic fluids) may result in low sodium levels in the blood (hyponatremia). This can cause headache, nausea, seizures, lethargy, coma, brain swelling (cerebral edema) and death; therefore, these symptoms (symptomatic acute hyponatremic encephalopathy) are considered a medical emergency. (See section 4. Possible side effects).

Children, women of childbearing age, and patients with brain diseases such as meningitis, cerebral hemorrhage, brain contusion, and cerebral edema have a special risk of suffering from severe and potentially fatal brain inflammation caused by acute hyponatremia.

Use of Potassium Chloride Kabi 0.04 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for Infusion with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. It is particularly important that you inform your doctor if you are taking:

• Medicines that may cause the amount of potassium in the blood to be too high due to an addition of effects, especially if your kidneys are not functioning correctly:
  • Potassium-sparing diuretics (amiloride, triamterene, spironolactone, eplerenone)
  • Angiotensin-converting enzyme inhibitors (ACE inhibitors) (such as captopril, enalapril, lisinopril)
  • Angiotensin II receptor antagonists (candesartan, telmisartan, eprosartan, irbesartan, losartan, valsartan)
  • Medicines that contain potassium such as potassium salts of penicillin
  • Non-steroidal anti-inflammatory drugs (NSAIDs) (diclofenac, indomethacin, piroxicam, mefenamic acid, celecoxib)
  • Heparin
  • Pentamidine, trimethoprim
  • Cyclosporine, tacrolimus
  • Beta-blockers (propranolol, nadolol, atenolol)
  • Succinylcholine (suxamethonium)

• Medicines that may reduce potassium levels in the blood, so higher doses of potassium may be needed:
  • Corticosteroids
  • Diuretics (loop diuretics, thiazides and related diuretics, osmotic diuretics, carbonic anhydrase inhibitors)
  • High doses of penicillins
  • Aminoglycosides
  • Cisplatin
  • Foscarnet
  • Amphotericin B
  • Theophylline
  • Insulin
  • Folic acid and vitamin B12
  • Beta-2 adrenergic agonists

• Digitalis glycosides (digoxin and methyldigoxin) (high potassium levels can reduce their effect and a sudden decrease in these levels can cause digitalis toxicity)
• Antiarrhythmic medicines (such as quinidine, hydroquinidine, procainamide) (high potassium levels increase their activity and low potassium levels reduce their effectiveness)
• Lithium carbonate (sodium can accelerate the renal excretion of lithium, leading to a decrease in its therapeutic effect)
• Corticosteroids with mineralocorticoid activity (such as fludrocortisone) or ACTH (corticotropin) (these medicines promote water and sodium retention)
• Corticosteroids with glucocorticoid activity (such as hydrocortisone) (these medicines can cause high blood glucose levels)
• Insulin and oral antidiabetics (biguanides, sulfonylureas) (glucose can reduce their effect).

• Medicines that lead to an increase in the effect of vasopressin (see the section on Warnings and Precautions), for example:
  • Medicines that stimulate the release of vasopressin (such as antipsychotics, narcotics)
  • Medicines that potentiate the action of vasopressin (such as non-steroidal anti-inflammatory drugs)
  • Medicines that act like vasopressin, the so-called vasopressin analogs

Other medicines that increase the risk of hyponatremia, including diuretics in general and antiepileptics.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine

The safety of its use during pregnancy and breastfeeding has not been established. Therefore, it should only be used when the beneficial effects clearly outweigh the possible risks to the fetus or baby.

This medicine should be administered with special caution in pregnant women during labor, especially if it is administered in combination with oxytocin (a hormone that can be administered to induce labor and control bleeding) due to the risk of hyponatremia.

Maternal administration of large amounts of glucose-containing solutions during labor, especially in complicated deliveries, can cause hyperglycemia, hyperinsulinemia (high insulin levels in the blood) and acidosis in the fetus and, consequently, can be harmful to the newborn.

Since this medicine contains sodium chloride, caution should be exercised in cases of preeclampsia during pregnancy.

If you are pregnant or breastfeeding, your doctor should continuously monitor your heart and potassium levels in the blood, as if they are not correct, serious cardiac disorders can occur in both the mother and the fetus or newborn.

Driving and using machines

Not relevant.

3. How to use Potassium Chloride Kabi 0.04 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for Infusion

This medicine will be given to you by a doctor or other healthcare professional through a drip (by infusion into a vein).

Your doctor will decide the dose you should receive, taking into account the severity of the hypokalemia, your age, weight, and clinical condition (especially if you have any heart or kidney disease), and how long you need to receive it.

The maximum recommended dose of potassium is 2-3 mEq/kg/day. In adults, the dose of potassium should not exceed 200 mEq per day. The recommended dose to meet maintenance requirements is 40-80 mEq per day.

Your doctor will decide the amount of fluid you should receive. However, in general, you should not receive more than 40 ml/kg/day (maximum 3000 ml per day).

The amount of glucose administered with the solution should not exceed 4-5 mg/kg/min.

If your kidneys are not functioning correctly, you should receive a lower dose.

As a general rule, the infusion rate should never exceed 20 mEq of potassium per hour when administered through a peripheral vein.

Use in children and adolescents

In children, the dose of potassium should not exceed 3 mEq/kg/day and the daily maintenance needs are 2-2.5 mEq/kg

The recommended daily fluid dose in these patients is as follows:

• less than 10 kg of weight: 100 ml/kg
• between 10 and 20 kg of weight: 1000 ml + 50 ml/kg that exceeds 10 kg
• more than 20 kg of weight: 1500 ml + 20 ml/kg that exceeds 20 kg

Oral administration of potassium supplements or ingestion of potassium-rich foods should replace intravenous administration of this medicine as soon as possible.

If you take more Potassium Chloride Kabi 0.04 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for Infusion than you should

Excessive administration of potassium solutions can cause hyperkalemia, which can be potentially fatal, especially if your kidneys are not functioning correctly. In case of overdose, alterations in fluid and electrolyte balance, swelling, and circulatory and cardiac disorders (see symptoms in section 4. Possible side effects) may also occur.

In case of hyperkalemia, your doctor should stop administration and take the most appropriate measures to reduce potassium levels in the blood.

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicology Information Service, phone: 91 562 04 20.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people will suffer from them.

After administration of this medicine, hyperhydration (fluid retention), hyperglycemia, hyperchloremic acidosis (high chloride content in the blood), and hyperkalemia may occur, especially if the solution is administered too quickly or in excess, or if your kidneys do not function properly. The symptoms of hyperkalemia mainly affect the nerves, muscles, and heart, and include itching or tingling of the extremities, muscle weakness, flaccid paralysis, respiratory paralysis, intestinal paralysis, mental confusion, loss of reflexes, apathy, cold skin, pallor (grayish skin tone), weakness, and heaviness of the legs, hypotension (low blood pressure), abnormalities in the electrocardiogram, abnormalities in heartbeats, cardiac block, and cardiac arrest. It is very important that your doctor monitors your heart to assess the severity of possible hyperkalemia.

Adverse effects derived from intravenous administration may also occur. These effects include fever, infection at the injection site, local pain, venous irritation, venous thrombosis (clot formation), inflammation, hardening, or contraction of the vein, extravasation, and necrosis (tissue death).

The following adverse effects may appear in some people:

• High levels of potassium and/or glucose in the blood, fluid retention, hyperchloremic acidosis
• Mental confusion, apathy
• Muscle weakness, itching or tingling of the extremities, loss of voluntary muscle movement (paralysis), loss of reflexes, feeling of weakness and heaviness
• Severe or total weakness of the respiratory muscles
• Intestinal obstruction due to lack of movement of the intestinal muscles
• Abnormalities in heartbeats, cardiac block, cardiac arrest
• Infection at the injection site
• Fever
• Inflammation, hardening, or contraction of the vein where the medicine is administered, venous thrombosis, cold skin, pallor (grayish skin tone), hypotension
• Pain, irritation, extravasation, and necrosis at the injection site
• Abnormalities in the electrocardiogram

Headache, nausea, convulsions, lethargy. This may be caused by a low level of sodium in the blood. When sodium levels in the blood drop significantly, water enters the brain cells and causes them to swell. This can cause an increase in cranial pressure and hyponatremic encephalopathy.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Conservation of Potassium Chloride Kabi 0.04 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for Infusion

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Store below 30°C.

Once the packaging is opened, the solution must be used immediately.

This medicine is for single use. Discard unused solution.

Do not use this medicine if you observe that the solution is not transparent or contains particles, or if the packaging is damaged.

Medicines should not be thrown away through drains or into the trash. Ask your pharmacist how to dispose of packaging and medicines that are no longer needed. This will help protect the environment.

6. Packaging Contents and Additional Information

Composition of Potassium Chloride Kabi 0.04 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for Infusion

• The active ingredients are potassium chloride, glucose, and sodium chloride. Each 100 ml of this medicine contains 0.3 g of potassium chloride, 3.3 g of glucose (as monohydrate), and 0.33 g of sodium chloride.
• The other components (excipients) are hydrochloric acid and sodium hydroxide (for pH adjustment) and water for injectable preparations.

Appearance of the Product and Packaging Contents

Potassium Chloride Kabi 0.04 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for Infusion is a clear and colorless solution.

This medicine is available in polyethylene vials (Kabipac). Boxes containing 10 vials of 500 ml or 10 vials of 1000 ml.

Only some packaging sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Fresenius Kabi España, S.A.U.

Marina 16-18,

08005 Barcelona

Spain

Manufacturer

Labesfal – Laboratórios Almiro, S.A.

Zona Industrial do Lagedo

3465-157 Santiago de Besteiros

Portugal

Date of the Last Revision of this Prospectus: March 2018

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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This information is intended only for healthcare professionals:

Potassium Chloride Kabi 0.04 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for Infusion is a ready-to-use solution that must be administered by slow infusion.

The theoretical osmolarity of the solution is 376 mOsm/l.

Given the potassium concentration of the solution (40 mEq/l), this medicine is suitable for administration through a peripheral vein. If a central vein is used, it is recommended to use the femoral vein and avoid the jugular and subclavian veins.

In general, it is recommended not to exceed 40 mEq/l via the peripheral route.

Dosage:

The dose and duration of treatment should be individualized for each patient, depending on the severity of hypokalemia, age, weight, and clinical condition, especially in cases of heart or kidney failure.

The dose and rate of administration should be determined by electrocardiographic monitoring and determination of plasma potassium levels.

In adults, the maximum recommended dose of potassium is 2-3 mEq/kg/day, not exceeding 200 mEq/day, with 40-80 mEq/day being the recommended dose in maintenance therapy.

Fluid administration should be calculated for each patient based on replacement or maintenance requirements. However, in general, no more than 40 ml/kg/day (max. 3000 ml per day) should be administered.

The amount of glucose administered with the solution should not exceed 4-5 mg/kg/min.

In children, the dose of potassium should not exceed 3 mEq/kg/day, and the daily maintenance requirements are 2-2.5 mEq/kg.

The recommended daily dose of fluid in these patients is as follows:

• < 10 kg of weight: 100 ml/kg
• between 10 and 20 kg of weight: 1000 ml + 50 ml/kg that exceeds 10 kg
• > 20 kg of weight: 1500 ml + 20 ml/kg that exceeds 20 kg

Patients with kidney failure should receive lower doses due to the risk of hyperkalemia.

The administration of intravenous potassium at a rate of 10 mEq/h is considered safe. When the administration rate is higher than 10 mEq/h, close monitoring of the patient will be performed using ECGs and periodic determinations of plasma potassium concentrations. As a general rule, the infusion rate via the peripheral route should never exceed 20 mEq/h. Via the central route, higher administration rates can be achieved.

General recommendations for the administration of intravenous potassium solutions:

Precautions for preparation and handling:

The contents of each vial are for single use. Unused contents should be discarded.

The solution should be transparent and not contain particles. Do not administer if this is not the case.

Use an aseptic technique to administer the solution, as well as to add medicines to the solution, if necessary.

As with all parenteral solutions, before adding medicines to the solution or administering them simultaneously with other medicines, it should be checked that there are no incompatibilities between the added medicines and the solution or the packaging. The technical data sheet of the added medicine should also be consulted.

Before administering the mixture, the stability and osmolarity of the final solution should be verified.

When compatible medication is added to this formulation, the solution should be administered immediately, unless the dilution has been carried out under controlled and validated aseptic conditions.

Incompatibilities:

No studies have been found that describe incompatibilities related to this medicine, but they have been found with the active ingredients of the solution.

Potassium chloride in intravenous mixtures has been shown to be incompatible with sodium amoxicillin, amphotericin B, dobutamine hydrochloride, and sodium penicillin G. Similarly, it is not recommended to administer the following drugs in a "Y" connection when administering potassium mixtures: azithromycin, promethazine hydrochloride, diazepam, sodium phenytoin, methylprednisolone sodium succinate, or ergotamine tartrate.

On the other hand, signs of incompatibility have been described when some medicines are diluted in solutions that contain glucose, including: sodium amoxicillin/clavulanic acid, sodium ampicillin, interferon alfa-2b, and procainamide hydrochloride. However, it should be noted that some of these drugs, such as sodium amoxicillin/clavulanic acid, can be injected directly into the injection point while these infusion solutions are being administered.

Signs of incompatibility have also been described when some medicines are diluted in solutions that contain chloride, including amsacrine and trimetrexate glucuronate.

Emergency Treatment in Case of Hyperkalemia:

Treatment of hyperkalemia depends on its severity. Different regimens have been established, consisting of the administration of calcium to counteract the negative effects of hyperkalemia on the heart, the use of insulin and glucose or sodium bicarbonate to promote the passage of potassium from outside the cell to the inside, and/or the use of diuretics, cation exchange resins, or dialysis to increase its excretion:

• If there are cardiac manifestations: administration of calcium salts by intravenous route (10-20 ml of 10% calcium gluconate). In some cases, a second administration may be necessary.

• To rapidly decrease plasma potassium: intravenous administration of insulin and glucose (e.g., 5-15 units of insulin along with 50 ml of 50% glucose). Alternatively or additionally, in acidotic patients, sodium bicarbonate can be administered intravenously (40-160 mEq administered in 5 minutes).

• To eliminate excess potassium from the body: use of diuretics, especially loop diuretics (furosemide), cation exchange resins (sodium or calcium polystyrene sulfonate) by rectal or oral route, or hemodialysis or peritoneal dialysis in cases of severe kidney failure and hypercatabolism.

A rapid decrease in plasma potassium levels in digitalized patients can cause cardiac toxicity due to digitalis.

Preventive measures to avoid thrombophlebitis:

If administration is prolonged, extravasation or thrombophlebitis may occur. To avoid thrombophlebitis, it is recommended to change the catheter insertion site every 24-48 hours.

General Advice

It may be necessary to monitor fluid balance, serum glucose, serum sodium, and other electrolytes before and during administration, especially in patients with increased release of non-osmotic vasopressin (inappropriate antidiuretic hormone secretion syndrome, SIADH) and in patients receiving concomitant medication with vasopressin agonists due to the risk of hyponatremia.

Monitoring of serum sodium is especially important in products with a lower sodium concentration compared to serum sodium concentration. After infusion of Potassium Chloride Kabi 0.04 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for Infusion, a rapid and active transport of glucose to the body's cells occurs. This condition promotes an effect that can be considered as a supply of free water and can lead to severe hyponatremia.