Potassium Grifols 0.02 mEq/ml in glucose 3.3% and sodium chloride 0.3% solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Potassium Grifols 0.02 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for infusion

Potassium chloride, Glucose, Sodium chloride

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or nurse.
• If you experience any side effects, consult your doctor or nurse, even if they are not listed in this leaflet. See section 4.

Leaflet contents

1. What Potassium Grifols 0.02 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for infusion is and what it is used for

2. What you need to know before using Potassium Grifols 0.02 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for infusion

3. How to use Potassium Grifols 0.02 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for infusion

4. Possible side effects

5. How to store Potassium Grifols 0.02 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for infusion

6. Contents of the pack and other information

1. What Potasio Grifols 0.02 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for infusion is and what it is used for

This medicine contains the following active substances: potassium chloride, glucose (as monohydrate), and sodium chloride. This medicine is an infusion solution and will be administered to you intravenously through a thin tube.

This medicine belongs to a group of medicines called intravenous solutions affecting electrolyte balance – electrolytes with carbohydrates (used to maintain body fluids in proper balance).

This medicine is indicated for the prevention or treatment of potassium deficiency (an electrolyte) in your body, when you require supplementation with water, electrolytes, and carbohydrates because dietary measures or oral medication are inadequate.

2. What you need to know before using Potassium Grifols 0.02 mEq/mL in Glucose 3.3% and Sodium Chloride 0.3% Solution for infusion

Do not use Potassium Grifols 0.02 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 to any of the other ingredients 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 output), anuria (absence of urine production), or azotemia (excess nitrogenous 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 have states of hyperhydration (excess water in the body)

• if you have hyperglycemic states (high blood glucose levels), such as hyperosmolar coma, uncontrolled diabetes, or other glucose intolerances as seen in metabolic stress situations

  • if you have renal tubular acidosis (a kidney function disorder)
  • if you have acute ischemic stroke (sudden loss of brain function due to blocked blood flow)
  • during the first 24 hours after head trauma.

Warnings and precautions

Talk to your doctor or nurse before using Potassium Grifols 0.02 mEq/mL in Glucose 3.3% and Sodium Chloride 0.3% Solution for infusion.

• Potassium administration must always be under strict medical supervision. During treatment with 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 your blood potassium levels, especially:

• if you have heart or kidney disease, or other conditions that may predispose you to hyperkalemia

• if you are taking other medicines that may increase blood potassium levels (see next subsection).

• Your doctor must exercise extreme caution if you are receiving digitalis drugs, particularly when stopping potassium administration, as a rapid drop in potassium levels may cause digitalis toxicity. In such cases, potassium therapy should not be discontinued abruptly.

• Potassium solution should only be administered if you have adequate urine output. If not, you may need to receive a potassium-free solution.

• Your doctor will perform frequent clinical and laboratory tests to monitor changes in fluid and acid-base balance, as well as electrolyte and blood glucose levels.

• This medicine may become physiologically hypotonic in the body due to the rapid metabolism of glucose (see section 3).

• Depending on the volume and rate of infusion, your initial clinical condition, and your ability to metabolize glucose, intravenous administration of this type of solution may cause electrolyte disturbances such as hyponatremia (low blood sodium levels).

Hyponatremia:

If you have non-osmotic release of vasopressin (antidiuretic hormone) (e.g., in critical illness, pain, postoperative stress, infections, burns, and central nervous system disorders), if you have heart, liver, or kidney disease, or if you are exposed to vasopressin agonists (see next subsection), you are at special risk of developing acute hyponatremia after receiving hypotonic solutions.

Acute hyponatremia may cause acute hyponatremic encephalopathy (cerebral edema), characterized by headache, nausea, seizures, lethargy, and vomiting. Patients with cerebral edema are at special risk of severe, irreversible, and potentially fatal brain damage.

Children, women of childbearing age, and patients with reduced cerebral compliance (e.g., meningitis, intracranial hemorrhage, or cerebral contusion) are at special risk of severe and potentially fatal cerebral edema due to acute hyponatremia.

• If you are in an emergency situation and your blood potassium levels are very low, or if you are taking digitalis medications, administration of glucose solutions is not recommended, as glucose may prevent potassium levels from rising as quickly as needed.

• If you have episodes of increased intracranial pressure, your doctor will closely monitor your blood glucose levels.

• Since this medicine contains glucose, it should be administered with caution if you have vitamin B1 deficiency or diabetes. Your doctor may administer this medicine only if appropriate treatment has been initiated beforehand.

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

• This medicine should be administered with special caution if you are elderly, as you may be taking other medications (see next subsection), or may have impaired kidney or heart function, or other conditions affecting blood potassium levels.

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

Other medicines and Potassium Grifols 0.02 mEq/mL in Glucose 3.3% and Sodium Chloride 0.3% Solution for infusion

It is very important that you inform your doctor if you are taking or have recently taken any of the following medicines:

? Medicines that may cause high blood potassium levels due to additive effects, especially if kidney function is impaired:

• 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 containing potassium, such as potassium salts of penicillin
• Non-steroidal anti-inflammatory drugs (NSAIDs) (diclofenac, indomethacin, piroxicam, mefenamic acid, celecoxib)
• Heparin
• Pentamidine, trimethoprim
• Cyclosporine, tacrolimus
• β-adrenergic blockers (propranolol, nadolol, atenolol)
• Succinylcholine (suxamethonium)

? Medicines that may reduce blood potassium levels, so higher potassium doses may be needed:

• Corticosteroids
• Diuretics (loop diuretics, thiazides and related agents, osmotic diuretics, carbonic anhydrase inhibitors)
• High doses of penicillins
• Aminoglycosides
• Cisplatin
• Foscarnet
• Amphotericin B
• Theophylline
• Insulin
• Folic acid and vitamin B12
• β2-adrenergic agonists

? Digitalis glycosides (digoxin and methyldigoxin) (high potassium levels may reduce their effect, and a sudden drop in potassium levels may cause digitalis toxicity)

? Antiarrhythmic medicines (such as quinidine, hydroquinidine, procainamide) (high potassium levels increase their activity, while low potassium levels reduce their effectiveness)

? Lithium carbonate (sodium may accelerate renal excretion of lithium, leading to reduced 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 may cause blood glucose levels to become too high)

? Insulin and oral antidiabetics (biguanides, sulfonylureas) (glucose may reduce their effect)

• Medicines that increase the effect of antidiuretic hormone (such as chlorpropamide, clofibrate, carbamazepine, vincristine, selective serotonin reuptake inhibitors, 3,4-methylenedioxy-N-methamphetamine, ifosfamide, antipsychotics, narcotics, NSAIDs (non-steroidal anti-inflammatory drugs), cyclophosphamide, desmopressin, oxytocin, vasopressin, terlipressin). These medicines reduce water excretion in urine and increase the risk of hospital-acquired hyponatremia after receiving inadequately balanced intravenous infusion solutions (see previous subsection and sections 3 and 4)
• Diuretics in general and antiepileptic drugs such as oxcarbazepine, which may increase the risk of hyponatremia.

Inform your doctor if you are using, have recently used, or might need to use any other medicine.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

The safety of this medicine during pregnancy and breast-feeding has not been established. Therefore, it should only be used when the beneficial effects clearly outweigh the potential risks to the fetus or infant.

Administration of large volumes of glucose-containing solutions to the mother during labor, especially in complicated deliveries, may cause hyperglycemia, hyperinsulinemia (high blood insulin levels), and acidosis in the fetus, and thus may be harmful to the newborn.

This medicine should be administered with special caution to pregnant women during labor, especially if administered in combination with oxytocin, due to the risk of hyponatremia (see previous subsections and section 4).

Due to the presence of sodium chloride in this medicine, extra caution should be taken in cases of preeclampsia during pregnancy.

If you are pregnant or breast-feeding, your doctor should continuously monitor your heart and blood potassium levels, as abnormalities could lead to serious cardiac disturbances in both mother and fetus or newborn.

Driving and using machines

Not applicable.

3. How to use Potassium Grifels 0.02 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for infusion

This medicine will be administered by a doctor or nurse in a hospital setting through a vein via drip (slow intravenous infusion).

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

You may need to be monitored for fluid balance, serum glucose, serum sodium, and other electrolytes before and during administration, particularly if you have non-osmotic vasopressin release (syndrome of inappropriate antidiuretic hormone secretion, SIADH), or if you are simultaneously receiving medications that are vasopressin agonists, due to the risk of hyponatremia. Monitoring of serum sodium is especially important when physiologically hypotonic solutions are administered. This medicine may become hypotonic after administration due to the rapid metabolism of glucose in the body (see sections 2 and 4).

The recommended maximum dose of potassium is 2–3 mEq/kg/day. In adults, the potassium dose 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 be given 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 properly, you will need to 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.

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

Use in children

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

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

• Less than 10 kg body weight: 100 ml/kg
• Between 10 and 20 kg body weight: 1000 ml + 50 ml/kg for each kg above 10 kg
• Over 20 kg body weight: 1500 ml + 20 ml/kg for each kg above 20 kg

If you receive more Potassium Grifels 0.02 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for infusion than you should

Excessive administration of potassium solutions may cause hyperkalemia, which can be potentially fatal, especially if your kidneys are not functioning properly. In case of overdose, disturbances in fluid balance and serum electrolytes may also occur, along with edema and circulatory and cardiac disturbances (see symptoms in section 4. Possible side effects).

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

In case of overdose or accidental ingestion, contact the Toxicology Information Service. Telephone: 915 620 420.

If you have any further questions about the use of this medicine, ask your doctor or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

After administration of this medicine, hyperhydration (fluid retention), hyperglycemia, hyperchloremic acidosis (high levels of chlorides in blood), and hyperkalemia may occur, especially if the solution is administered too rapidly or in excess, or if your kidneys are not functioning properly. Symptoms of hyperkalemia mainly affect nerves, muscles, and the 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 in the legs, hypotension (low blood pressure), abnormalities in the electrocardiogram, irregular heartbeats, cardiac block, and cardiac arrest. It is very important that your doctor monitor your heart to assess the severity of possible hyperkalemia.

Patients with non-osmotic release of vasopressin, patients with heart, liver, or kidney diseases, and patients treated with vasopressin agonists have a special risk of developing acute hyponatremia after administration of hypotonic solutions. Hospital-acquired hyponatremia can cause irreversible brain damage and death due to cerebral edema (see sections 2 and 3).

Adverse effects related to 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 constriction of the vein, extravasation, and necrosis (tissue death).

The following adverse effects may occur in some people:

• Elevated levels of potassium and/or glucose in 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, sensation of weakness and heaviness
• Severe or complete weakness of respiratory muscles
• Intestinal obstruction due to lack of movement of intestinal muscles
• Abnormalities in heartbeats, cardiac block, cardiac arrest
• Low levels of sodium in blood (acquired during hospitalization)
• Cerebral edema
• Infection at the injection site
• Fever
• Inflammation, hardening or constriction 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.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or nurse, even if they are possible adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Potassium Grifols 0.02 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 expiry date stated on the container. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

Once the container has been opened, the solution should be used immediately.

This medicine is for single use only. Discard any unused solution.

Do not use this medicine if you notice that the solution is not clear, contains particles, or if the container is damaged.

6. Package contents and other information

Composition of Potassium Grifols 0.02 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for infusion

• The active substances are potassium chloride, glucose, and sodium chloride. Each 100 ml of this medicinal product contains 0.149 g of potassium chloride, 3.3 g of glucose (as monohydrate), and 0.3 g of sodium chloride.
• The other components (excipients) are hydrochloric acid (for pH adjustment) and water for injections.

Appearance of the product and contents of the container

Potassium Grifols 0.02 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% is a solution for infusion. It is a clear, colorless aqueous solution.

This medicinal product is available in flexible bags made of polypropylene (Fleboflex) (in cartons containing 20 bags of 500 ml or 10 bags of 1000 ml).

Marketing Authorization Holder

Laboratorios Grifols, S.A.

Can Guasch, 2

08150 Parets del Vallès, Barcelona (SPAIN)

Manufacturer

LABORATORIOS GRIFOLS, S.A.

Polígono Los Llanos. C/Marte 4

30565 Las Torres de Cotillas, Murcia (SPAIN)

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Date of the most recent review of this summary: July 2018

Other sources of information

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (Agencia Española de Medicamentos y Productos Sanitarios, AEMPS) (http://www.aemps.gob.es/)

This information is intended for healthcare professionals only:

Potassium Grifols 0.02 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 326 mOsm/L.

Given the potassium concentration of the solution (20 mEq/L), this medicinal product is suitable for administration via peripheral vein. If a central vein is used, the femoral vein is recommended and jugular and subclavian routes should be avoided.

In general, it is recommended not to exceed 40 mEq/L via peripheral administration.

Dosage:

The dose and duration of treatment must be individualized for each patient, depending on the severity of hypokalaemia, age, weight, and clinical condition, especially in cases of cardiac or renal failure.

Monitoring of fluid balance, serum glucose, serum sodium, and other electrolytes may be required before and during administration, particularly in patients with increased non-osmotic release of vasopressin (syndrome of inappropriate antidiuretic hormone secretion, SIADH) and in patients receiving concomitant treatment with vasopressin agonists, due to the risk of hyponatraemia. Monitoring of serum sodium is especially important when physiologically hypotonic solutions are administered. Potassium Grifols 0.02 mEq/mL in Glucose 3.3% and Sodium Chloride 0.3% may become hypotonic after administration due to the rapid metabolism of glucose in the body.

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

In adults, the recommended maximum dose of potassium is 2–3 mEq/kg/day, without exceeding 200 mEq/day; the recommended dose for maintenance therapy is 40–80 mEq/day.

Fluid administration should be calculated individually based on rehydration or maintenance requirements. However, in general, no more than 40 mL/kg/day (maximum 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 potassium dose should not exceed 3 mEq/kg/day, and daily maintenance requirements are 2–2.5 mEq/kg.

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

• < 10 kg body weight: 100 mL/kg
• between 10 and 20 kg body weight: 1000 mL + 50 mL/kg for each kg above 10 kg

• 20 kg body weight: 1500 mL + 20 mL/kg for each kg above 20 kg

Patients with renal impairment should receive lower doses due to the risk of developing hyperkalaemia.

Intravenous potassium administration at a rate of 10 mEq/hour is considered safe. When the administration rate exceeds 10 mEq/hour, close patient monitoring with ECGs and periodic measurements of plasma potassium concentrations should be performed. As a general rule, the infusion rate via peripheral vein must never exceed 20 mEq/hour. Higher administration rates may be achieved via central vein.

General recommendations for the administration of intravenous potassium solutions:

Preparation and handling precautions:

The contents of each container are for single use only. Any unused content must be discarded.

The solution should be clear and free from particles. Do not administer if this is not the case.

Check for the absence of small leaks by firmly pressing the bag. If leaks are detected, discard the product.

To connect the infusion set, remove the protective tab from the infusion port, thereby exposing the access membrane to the bag.

Use an aseptic technique when administering the solution and when adding medications to the solution, if necessary.

As with all parenteral solutions, before adding medications to the solution or administering them concomitantly with other drugs, compatibility must be verified to ensure there are no incompatibilities between the added drugs and the solution or its container. The package leaflet of the added medication should also be consulted.

It is the user's responsibility to evaluate the incompatibility of the added medication with Potassium Grifols 0.02 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for infusion, monitoring for possible changes in color and/or formation of precipitates, insoluble complexes, or crystals.

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

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

Incompatibilities:

No studies describing incompatibilities related to this medicinal product have been found, but some exist concerning the active substances 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. Furthermore, the "Y-site" administration of the following drugs is not recommended when potassium-containing mixtures are being administered: azithromycin, promethazine hydrochloride, diazepam, sodium phenytoin, sodium methylprednisolone succinate, or ergotamine tartrate.

It has been reported that the glucosaline solution containing 3.3% glucose and 0.3% sodium chloride is incompatible with mitomycin due to the low pH of this solution. In addition, incompatibility has been observed in various glucosaline solutions with the following: sodium phenytoin, sodium heparin, haloperidol lactate, sodium imipenem-cilastatin, and meropenem. However, some of these drugs may be compatible with glucosaline solutions depending on various factors such as drug concentration in the solution (sodium heparin) or the time interval between reconstitution and administration (sodium imipenem-cilastatin and meropenem).

Moreover, incompatibility signs have been described when certain medications are diluted in glucose-containing solutions, 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, may be directly injected at the injection site while these infusion solutions are being administered.

Incompatibility signs have also been described when certain medications are diluted in chloride-containing solutions, including amsacrine and trimetrexate glucuronate.

Emergency treatment in case of hyperkalemia:

Treatment of hyperkalemia depends on its severity. Different regimens have been established, involving administration of calcium to counteract the adverse cardiac effects of hyperkalemia, use of insulin and glucose or sodium bicarbonate to promote the shift of extracellular potassium into cells, and/or use of diuretics, cation-exchange resins, or dialysis to enhance potassium excretion:

• If cardiac manifestations are present: intravenous administration of calcium salts (10–20 mL of 10% calcium gluconate). In some cases, a second dose may be required.

• To rapidly reduce plasma potassium levels: intravenous administration of insulin and glucose (e.g., 5–15 units of insulin together with 50 mL of 50% glucose). Alternatively or additionally, in acidotic patients, intravenous sodium bicarbonate (40–160 mEq administered over 5 minutes) may be given.

• To eliminate excess potassium from the body: use of diuretics, especially loop diuretics (furosemide), cation-exchange resins (sodium or calcium polystyrene sulfonate) administered orally or rectally, or hemodialysis or peritoneal dialysis in severe cases of renal failure and hypercatabolism.

A rapid decrease in plasma potassium levels in digitalized patients may lead to digitalis-related cardiac toxicity.

Preventive measures to avoid thrombophlebitis:

Prolonged administration may result in extravasation or thrombophlebitis. To prevent thrombophlebitis, it is recommended to rotate the catheter insertion site every 24–48 hours.