Potassium Grifols 0.04 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 0.04 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, because 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 adverse reactions, consult your doctor or nurse, even if they are not listed in this leaflet. See section 4.

Leaflet contents

1. What Potassium Grifols 0.04 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 0.04 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for infusion
3. How to use Potassium Grifols 0.04 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for infusion
4. Possible side effects
5. How to store Potassium Grifols 0.04 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for infusion
6. Contents of the pack and other information

1. What Potassium Grifols 0.04 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 the 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 supplementation of water, electrolytes and carbohydrates is required because dietary measures or oral medication are inadequate.

2. What you need to know before using Potassium Grifols 0.04 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% Solution for infusion

Do not use Potassium Grifols 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 to any of the other ingredients of this medicine (listed in section 6)

• if your blood potassium levels are high (hyperkalemia)

• if you have a 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 0.04 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 to detect early signs of excessive potassium levels (hyperkalemia), your doctor will monitor your heart using 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 glycosides, particularly when stopping potassium administration, as a rapid decrease in potassium levels may cause digitalis toxicity. In such cases, potassium treatment 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 solution without potassium.

• 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 such solutions may cause electrolyte disturbances such as hyponatremia (low blood sodium levels).

Hyponatremia:

If you have non-osmotic vasopressin release (antidiuretic hormone) (e.g., in critical conditions, 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 administration of 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 glycosides, administration of glucose-containing solutions is not recommended, as glucose may prevent potassium levels from rising as rapidly 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 hypertension 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 that may affect blood potassium levels.

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

Other medicines and Potassium Grifols 0.04 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 blood potassium levels to become too high 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, thus requiring higher potassium doses:

• 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, cyclophosphamide, desmopressin, oxytocin, vasopressin, terlipressin). These medicines reduce water excretion in urine and increase the risk of hospital-acquired hyponatremia after inadequately balanced intravenous infusion therapy (see previous subsection and sections 3 and 4)

• Diuretics in general and antiepileptic medicines 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 medicines.

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 its use 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 fetal hyperglycemia, hyperinsulinemia (high blood insulin levels), and acidosis, and thus may be harmful to the newborn.

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

Because this medicine contains sodium chloride, extreme caution should be exercised 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 0,04 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 decide 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 be treated.

Your fluid balance, serum glucose, serum sodium, and other electrolytes may need to be monitored before and during administration, particularly if you have non-osmotic release of vasopressin (syndrome of inappropriate antidiuretic hormone secretion, SIADH), or if you are simultaneously receiving medications with 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 daily. The recommended dose to meet maintenance requirements is 40–80 mEq per day.

Your doctor will determine the amount of fluid you should receive. However, in general, you should not be administered 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 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.

Oral administration of potassium supplements or intake 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 0.04 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, swelling, and circulatory and cardiac disturbances may also occur (see symptoms in section 4. Possible side effects).

In case of hyperkalemia, your doctor should 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 may cause adverse effects, although not everyone experiences them.

After administration of this medicine, overhydration (fluid retention), hyperglycemia, hyperchloremic acidosis (high blood chloride levels), 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 in 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), electrocardiogram abnormalities, cardiac rhythm disturbances, heart 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 disease, and patients treated with vasopressin agonists are at special risk of developing acute hyponatremia after administration of hypotonic solutions. Hospital-acquired hyponatremia may 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 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 occur in some people:

• Elevated levels of potassium and/or glucose in the blood, fluid retention, hyperchloremic acidosis
• Mental confusion, apathy
• Muscle weakness, itching or tingling in 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 intestinal muscle movement
• Cardiac rhythm abnormalities, heart block, cardiac arrest
• Low blood sodium levels (acquired during hospitalization)
• Cerebral edema
• 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
• Electrocardiogram abnormalities

Reporting of adverse effects

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

5. Storage of Potassium Grifols 0.04 mEq/ml in 3.3% Glucose and 0.3% Sodium Chloride 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. Any unused solution should be discarded.

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

6. Contents of the pack and other information

Composition of Potassium Grifols 0.04 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 0.298 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 0.04 mEq/ml in Glucose 3.3% and Sodium Chloride 0.3% is a solution for infusion. It is a clear, colourless aqueous solution.

This medicinal product is available in flexible polypropylene bags (Fleboflex) (in packs 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 medicine is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/)

This information is intended for healthcare professionals only:

Potassium Grifols 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 366 mOsm/L.

Given the potassium concentration of the solution (40 mEq/L), this medicine is suitable for administration via peripheral vein. If a central vein is used, the femoral vein is recommended and the jugular and subclavian veins should be avoided.

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

Dosage:

The dose and duration of treatment must be individualized for each patient depending on the severity of hypokalemia, 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 medications with vasopressin agonists, due to the risk of hyponatremia. Monitoring of serum sodium is especially important when physiologically hypotonic solutions are administered. Potassium Grifols 0.04 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 measurement 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 for each patient 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 hyperkalemia.

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

General recommendations for the administration of intravenous potassium solutions:

Precautions for preparation and handling:

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 otherwise.

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, as well as when adding medications to the solution, if necessary.

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

It is the user's responsibility to evaluate the incompatibility of any added drug with Potassium Grifols 0.04 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.

Prior to administration of 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 dilution was performed under controlled, validated aseptic conditions.

Incompatibilities:

No studies describing incompatibilities related to this medicinal product have been found, although some exist concerning the active substances in the solution.

Potassium chloride in intravenous mixtures has been shown to be incompatible with sodium amoxicillin, amphotericin B, dobutamine hydrochloride, and sodium penicillin G. Additionally, administration via Y-site is not recommended for the following drugs when potassium-containing mixtures are being administered: azithromycin, promethazine hydrochloride, diazepam, sodium phenytoin, sodium methylprednisolone succinate, or ergotamine tartrate.

The glucosaline solution containing 3.3% glucose and 0.3% sodium chloride has been reported to be incompatible with mitomycin due to the low pH of this solution. In addition, incompatibility has been observed in various glucosaline solutions with the following drugs: 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 elapsed between solution preparation and administration (sodium imipenem-cilastatin and meropenem).

Furthermore, signs of incompatibility have been described when certain drugs are diluted in solutions containing 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, may be directly injected into the injection site while these infusion solutions are being administered.

Signs of incompatibility have also been described when certain drugs are diluted in solutions containing chloride, including amsacrine and trimetrexate glucuronate.

Emergency treatment in case of hyperkalemia:

Treatment of hyperkalemia depends on its severity. Different regimens have been established, including 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:

• In the presence of cardiac manifestations: 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 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, particularly 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 precipitate cardiac toxicity due to digitalis.

Preventive measures to avoid thrombophlebitis:

If administration is prolonged, extravasation or thrombophlebitis may occur. To prevent thrombophlebitis, it is recommended to rotate the catheter insertion site every 24–48 hours.