DIGOXIN KERN PHARMA 0.25 mg/ml INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Digoxina Kern Pharma 0.25 mg/ml Solution for Injection

Contents of the Package Leaflet:

1. What is Digoxina Kern Pharma and what is it used for
2. What you need to know before you start using Digoxina Kern Pharma
3. How to use Digoxina Kern Pharma
4. Possible side effects
5. Storage of Digoxina Kern Pharma
6. Contents of the pack and further information

1. What is Digoxina Kern Pharma and what is it used for

Digoxina Kern Pharma belongs to a group of medicines called cardiac glycosides. Its active ingredient is digoxin, which increases the strength of the heart muscle's contraction by specifically inhibiting an enzyme called Na+/K+ dependent adenosine triphosphatase.

This medicine is indicated for the treatment of certain heart problems, such as:

• "Chronic heart failure" where the main problem is "systolic dysfunction" (alterations in the heart's contraction),
• when heart failure is accompanied by "atrial fibrillation" (abnormal heart rhythm or frequency that originates when the muscle of the heart's upper chambers (atria) does not contract uniformly),
• in the treatment of certain "supraventricular arrhythmias" (disorders of heart rate or rhythm that originate in the atria), especially atrial flutter (rapid heart rate) and atrial fibrillation (abnormal heart rhythm or frequency that originates when the muscle of the heart's upper chambers (atria) does not contract uniformly), with the main benefit being the reduction of ventricular rate (slower heart rate).

2. What you need to know before you start using Digoxina Kern Pharma

Do not use Digoxina Kern Pharma

• if you are allergic to digoxin, other digitalis glycosides, or any of the other ingredients of this medicine,
• if you have been told that you have any of the following heart problems:
• • intermittent cardiac block or second-degree atrioventricular block (alterations in the transmission of the electrical impulse between the heart's upper and lower chambers), especially if there is a history of a heart disease called Stokes-Adams syndrome,
  • certain types of "supraventricular arrhythmias", such as in the case of Wolff-Parkinson-White syndrome (a hereditary heart disease),
  • "ventricular tachycardia" (rapid heart rate that starts in the ventricles) or "ventricular fibrillation" (very abnormal heart rhythm that can be fatal),
  • "hypertrophic obstructive cardiomyopathy" (a disease in which there is excessive growth of the heart muscle),
• in case of arrhythmias caused by poisoning with other cardiac glycosides (heart medicines),
• if you know or suspect that you have an accessory pathway (abnormal electrical communication between the atrium and ventricle) and there is no history of previous supraventricular arrhythmias, this medicine is also contraindicated.

Warnings and precautions

This medicine must be used exclusively under medical supervision and control. Consult your doctor before starting to use this medicine in any of the following cases:

• if you have recently had a myocardial infarction, digoxin should be taken with caution,
• if you are being treated with diuretics and an ACE inhibitor (heart and hypertension medicines), or only diuretics, since when digoxin administration is discontinued, your disease may worsen,
• if you have taken cardiac glycosides (heart medicines) two weeks before starting treatment with digoxin, your doctor should consider reducing the initial dose,
• if administered to elderly patients or patients with decreased renal function, the doctor should consider reducing both the initial dose and the maintenance dose,
• when you are already being treated with digoxin, your doctor should periodically check your serum electrolytes and renal function (serum creatinine concentration). The frequency of checks will depend on the severity of the case,
• if you have severe respiratory disease, since the myocardium (heart muscle) may be more sensitive to digoxin,
• if you have low potassium levels in the blood, since this causes the myocardium (heart muscle) to be more sensitive to the actions of digoxin,
• if you have hypoxia (low oxygen levels in the blood), hypomagnesemia (low magnesium levels in the blood), and marked hypercalcemia (high calcium levels in the blood), since these increase the sensitivity of the myocardium (heart muscle) to digoxin,
• if you have thyroid disease, you should be cautious when using this medicine. The initial and maintenance doses of digoxin should be reduced when thyroid function is deficient. In the case of hyperthyroidism (high levels of thyroid hormone in the blood), there is a relative resistance to digoxin (lower activity of this medicine) and the dose may need to be increased. During treatment of thyrotoxicosis (excess of thyroid hormones), the dose should be reduced as the disease is controlled,
• patients with malabsorption syndrome (difficulty absorbing vitamins, minerals, and other nutrients from food) or gastrointestinal reconstructions may require higher doses of digoxin.

Using Digoxina Kern Pharma with other medicines

Tell your doctor or pharmacist if you are using or have recently used or may need to use any other medicines.

Agents that cause hypokalemia or intracellular potassium deficiency may increase sensitivity to Digoxina; these include some diuretics (medicines to facilitate fluid elimination), lithium salts, corticosteroids (anti-inflammatory medicines), and carbenoxolone (medicine for the treatment of mouth ulcers).

Digoxin blood levels may increase with the concomitant administration of the following medicines:

• Amiodarone, flecainide, prazosin, propafenone, quinidine, spironolactone (heart medicines).
• Calcium channel blockers and ACE inhibitors (hypertension medicines).
• Erythromycin, tetracycline, gentamicin, itraconazole, trimethoprim (antibiotic medicines).
• Quinine (medicine for the treatment of malaria).
• Alprazolam, lithium salts (medicine for depression).
• Diphenoxylate with atropine (combination of medicines used as an antidiarrheal).
• Indomethacin.
• Propantheline (medicine for the treatment of ulcers).

Digoxin blood levels may decrease with the concomitant administration of the following medicines:

• Antacids.
• Some laxatives.
• Kaolin-pectin (antidiarrheal medicine).
• Neomycin, penicillamine, rifampicin (antibiotic medicines).
• Some cytostatics (cancer treatment medicines).
• Metoclopramide (medicine for the treatment of vomiting).
• Sulfasalazine (anti-inflammatory medicine for the stomach).
• Adrenaline (a hormone).
• Salbutamol (medicine for the treatment of asthma).
• Colestyramine (medicine for the treatment of cholesterol).
• Phenytoin (medicine for the treatment of epilepsy).

Tell your doctor if you are taking a medicine that contains enzalutamide (for the treatment of prostate cancer). It may interfere with your digoxin tests.

Pregnancy, breastfeeding, and fertility

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

As with all medicines, the use of digoxin during pregnancy should only be considered when the expected clinical benefit to the mother outweighs any possible risk to the fetus.

Although digoxin passes into breast milk, the amounts are minimal.

Digoxina solution for injection contains ethanol, and this should be taken into account in the case of pregnant or breastfeeding women (see section 2 – "Digoxina Kern Pharma contains ethanol").

Driving and using machines

No data are available on how digoxin affects the ability to drive or use machines, so be careful not to perform tasks that require special attention until you know how you tolerate the medicine.

The propylene glycol contained in this medicine may produce effects similar to those produced by alcohol and increase the likelihood of these adverse effects. This may decrease the ability to drive or use machines.

Digoxina Kern Pharma contains ethanol

This medicine contains 83.86 mg of ethanol per ml. This amount is equivalent to less than 2.1 ml of beer or 0.9 ml of wine.

This small amount of alcohol in this medicine does not have noticeable effects.

Digoxina Kern Pharma contains propylene glycol (E-1520)

This medicine contains 830 mg of propylene glycol per 2 ml (1 ampoule).

Use this medicine only if your doctor has recommended it. Your doctor may perform additional checks while you are taking this medicine.

3. How to use Digoxina Kern Pharma

Follow exactly the administration instructions of this medicine indicated by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again.

The dose of digoxin for each patient must be established individually according to age, body weight, and renal function. The suggested doses are only intended to serve as an initial guide.

Your doctor should take into account the difference in effects between the administration of digoxin in oral and injectable forms when changing from one pharmaceutical form to another. For example, if a patient is switched from an oral formulation to an intravenous one, the dose should be reduced by at least 33%.

The normal dose is:

Adults and children over 10 years:

Parenteral emergency loading dose (in patients who have not received cardiac glycosides in the previous two weeks):

The loading dose of digoxin by parenteral route is 500 to 1000 micrograms (0.5 to 1.0 mg) depending on age, body weight, and renal function.

The loading dose should be administered in divided doses, with approximately half of the total dose given in the first dose and additional fractions of the total dose at intervals of 4 to 8 hours, evaluating the clinical response before administering each additional dose. Each dose should be administered by intravenous infusion (see Dilution) over 10-20 minutes.

Newborns, infants, and children under 10 years (if they have not received cardiac glycosides in the previous two weeks):

• Parenteral emergency loading dose:

The doses in children depend on their weight.

However, these doses are between 20 and 35 micrograms over 24 hours.

The loading dose should be administered in divided doses, with approximately half of the total dose given in the first dose and additional fractions of the total dose at intervals of 4 to 8 hours, evaluating the clinical response before administering each additional dose. Each dose should be administered by intravenous infusion (see Dilution) over 10-20 minutes.

• Maintenance dose:

Your doctor will indicate what the maintenance dose is, depending on the child's response to the initial treatment with this medicine.

On average, most patients will be maintained between 20% and 25% of the loading dose, administered every 24 hours.

If you use more Digoxina Kern Pharma than you should

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

If you forget to use Digoxina Kern Pharma

Do not use a double dose to make up for forgotten doses.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, digoxin can cause side effects, although not everybody gets them.

In general, adverse reactions to digoxin are dose-dependent and occur at doses higher than those required to achieve a therapeutic effect. Consequently, adverse reactions are less common when digoxin is used within the recommended dose range or within the therapeutic concentration range in serum and careful attention is paid to the conditions and medication administered concurrently.

Cardiac disorders:

Cardiac arrhythmias and alterations in the electrical conduction of the heart, including:

• Ventricular contractions that precede the normal heart rhythm and may evolve into bigeminism (alteration of the heart rhythm in which normal heartbeats alternate with premature beats) or even trigeminism (alteration of the heart rhythm in which two normal heartbeats alternate with a premature beat).
• Atrial tachycardias (disorder of heart rhythm, such as rapid heartbeats that originate in the heart's upper chambers). It is common for them to be accompanied by atrioventricular block (disorder in the electrical conduction between the atria and ventricles) and not always a rapid pulse (see section 2).
• Alterations in the electrocardiogram result.
• Sinus bradycardia (disorder that produces a decrease in the heart rate). Especially in children, it can be a sign of impending digoxin intoxication.

Gastrointestinal disorders:

Anorexia, nausea, and vomiting that disappear a few hours after taking the medicine. Diarrhea may also appear.

Digoxin administered orally has also been associated with intestinal ischemia (interruption of blood supply to the intestine) and, rarely, with intestinal necrosis (death of part of the intestine due to interruption of blood supply).

Reproductive system and breast disorders:

Gynecomastia (development of breast tissue in men) may occur with long-term administration.

Nervous system disorders:

Weakness, apathy, fatigue, malaise, headache, vision changes, depression, and even psychosis have been reported.

Skin and subcutaneous tissue disorders:

Urticaria-like (red, itchy rashes on the skin) or scarlatiform (generalized redness of the skin with small, raised lesions) skin rashes.

Blood and lymphatic system disorders:

Marked eosinophilia (increase in the number of white blood cells in the blood).

Thrombocytopenia (decrease in the number of platelets in the blood).

Pediatric population

The side effects of digoxin in infants and children differ from those observed in adults in several aspects. Although digoxin can cause anorexia, nausea, vomiting, diarrhea, and CNS alterations in young patients, these are rarely the initial symptoms of an overdose. Instead, the earliest and most frequent manifestation of excessive dosing with digoxin in infants and children is the appearance of cardiac arrhythmias, including sinus bradycardia.

In children, the use of digoxin can cause any type of arrhythmia. The most common are alterations in conduction or supraventricular tachyarrhythmias, such as atrial tachycardia (with or without block) and atrioventricular nodal tachycardia. Ventricular arrhythmias are less common.

Sinus bradycardia can be a sign of impending digoxin intoxication, especially in children, even in the absence of first-degree cardiac block. It should be assumed that any arrhythmia or conduction alteration that develops in a child taking digoxin is caused by digoxin, until a subsequent evaluation proves otherwise.

If you experience side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet.

5. Storage of Digoxina Kern Pharma

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

No special storage conditions are required.

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

Medicines should not be disposed of via wastewater or household waste. Place the packaging and any unused medicines in the pharmacy's SIGRE point. If you are unsure, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Container Content and Additional Information

Composition ofDigoxin Kern Pharma

• The active ingredient is digoxin.
• The other components are: ethanol, propylene glycol (E-1520), citric acid monohydrate, anhydrous sodium hydrogen phosphate, and water for injectable preparations.

Appearance of the Product and Container Content

Injectable solution.

Each container contains 5 ampoules of 2 ml.

Other Presentations

• Digoxin Kern Pharma 0.25 mg tablets. Containers containing 50 tablets.
• Digoxin 0.05 mg/ml pediatric oral solution marketed under the name Lanacordin Pediatric. 60 ml container with a dosing syringe.

Marketing Authorization Holder and Manufacturer

Kern Pharma, S.L.

Pol. Ind. Colón II, C/Venus, 72

08228 Terrassa (Barcelona)

Spain

Date of the Last Revision of this Prospectus:August 2025

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

This information is intended only for doctors or healthcare professionals:

The greatest therapeutic benefit of digoxin is obtained in patients with ventricular dilation.

METHOD OF ADMINISTRATION:

The intramuscular route is painful and is associated with muscle necrosis (death of cardiac muscle cells). This route cannot be recommended.

Rapid intravenous injection can cause vasoconstriction, producing hypertension and/or reduction of coronary flow. Therefore, slow injection speed is important in hypertensive heart failure and acute myocardial infarction.

Adults and Children Over 10 Years:

Parenteral Emergency Loading(in patients who have not received cardiac glycosides in the previous two weeks):

The loading dose of digoxin by parenteral route is 500 to 1000 micrograms (0.5 to 1.0 mg) depending on age, net body weight, and renal function.

The loading dose should be administered in divided doses, with approximately half of the total dose given in the first dose and additional fractions of the total dose at intervals of 4 to 8 hours, evaluating the clinical response before administering each additional dose. Each dose should be administered by intravenous infusion (see Dilution) for 10-20 minutes.

Newborns, Infants, and Children Under 10 Years (if they have not received cardiac glycosides in the preceding two weeks):

• Parenteral Emergency Loading:

The doses in children depend on their weight.

However, these doses are between 20 and 35 micrograms over 24 hours.

The loading dose should be administered in divided doses, with approximately half of the total dose given as the first dose and additional fractions of the total dose at intervals of 4 to 8 hours, evaluating the clinical response before administering each additional dose. Each dose should be administered by intravenous infusion (see Dilution) for 10-20 minutes.

• Maintenance:

Your doctor will indicate what the maintenance dose is, depending on the child's response to initial treatment with digoxin.

On average, most patients will be maintained between 20% and 25% of the loading dose, administered every 24 hours.

In newborns, especially premature infants, the renal clearance of digoxin is decreased, and appropriate dose reductions should be considered, above the general dosing instructions.

After the newborn phase, children generally require proportionally higher doses than adults based on weight or body surface area, as indicated in the following table. Children over 10 years require adult doses proportional to their body weight.

• Intravenous Loading Dosein the above groups:

This should be administered according to the following program:

The loading dose should be administered in divided doses, with approximately half of the total dose given as the first dose and additional fractions of the total dose at intervals of 4 to 8 hours, evaluating the clinical response before administering each additional dose. Each dose should be administered by intravenous infusion (see Dilution) for 10-20 minutes.

• Maintenance:

The maintenance dose should be administered according to the following program:

Preterm newborns:

• daily dose = 20% of the 24-hour loading dose (intravenous or oral).

Full-term newborns and children up to 10 years:

• daily dose = 25% of the 24-hour loading dose (intravenous or oral).

These dosing schemes are designed to be a guideline, and careful clinical observation and monitoring of digoxin serum levels (see Control) should be performed to adjust the dose in these pediatric patient groups.

If cardiac glycosides have been administered in the two weeks prior to the start of treatment with this medication, it should be anticipated that the optimal loading doses of digoxin will be lower than those recommended above.

Digitalis glycosides are a significant cause of accidental poisoning in children. The tolerance of newborns to digitalis glycosides is variable since the renal clearance of the medication is reduced. Premature and immature newborns are especially sensitive.

Elderly Patients:

The tendency to altered renal function and low net body mass in elderly patients influences the pharmacokinetics of digoxin such that elevated serum digoxin levels and associated toxicity may easily appear, unless lower doses of digoxin are used than those used in non-elderly patients. Digoxin serum levels should be regularly monitored, and hypokalemia should be avoided.

Dosing Recommendations in Specific Patient Groups:

See the "Warnings and Precautions" section.

Dilution of Digoxin Kern Pharma:

This medication can be administered undiluted or diluted with a diluent volume four times greater or more. The use of a volume less than four times the volume of the diluent could lead to the precipitation of digoxin.

It is known that this medication, when diluted in a 1:250 ratio (for example, one 2 ml ampoule with 500 micrograms added to 500 ml of infusion solution), is compatible with the following infusion solutions, remaining stable for up to 48 hours at room temperature (20 to 25°C):

• Intravenous Infusion of Sodium Chloride, B.P., 0.9% p/v.
• Intravenous Infusion of Sodium Chloride (0.18% p/v) and Glucose (4% p/v), B.P.
• Intravenous Infusion of Glucose, B.P., 5% p/v.

Dilution should be performed either under completely aseptic conditions or immediately before use. Any unused solution should be discarded.

Control:

Digoxin serum concentrations can be expressed in Conventional Units of ng/ml or in SI Units of nmol/l. To convert ng/ml to nmol/l, multiply ng/ml by 1.28.

The serum concentration of digoxin can be determined by radioimmunoassay. Blood should be drawn every 6 hours or more after the last dose of this medication. There are no strict guidelines on the interval of serum concentrations that are most effective, but most patients will benefit, with little risk of developing signs and symptoms of toxicity, with digoxin concentrations between 0.8 ng/ml (1.02 nmol/l) and 2.0 ng/ml (2.56 nmol/l). Above this interval, signs and symptoms of toxicity may be more frequent, and levels above 3.0 ng/ml (3.84 nmol/l) are likely to be toxic. However, to decide whether a patient's symptoms are due to digoxin, the clinical condition, along with the serum potassium level and thyroid function, are important factors to consider.

Other glycosides, including digoxin metabolites, may interfere with available assays, so caution should be exercised with values that do not seem to be in agreement with the patient's clinical condition.

SYMPTOMS OF OVERDOSAGE AND TREATMENT:

Adults:

In adults without heart disease, clinical observation indicates that a digoxin overdose of 10-15 mg was the dose that led to death in half of the patients. If an adult without heart disease ingested more than 25 mg of digoxin, it would result in death or progressive toxicity that would only respond to the administration of antibody fragments that bind to digoxin.

Children:

In children from 1 to 3 years without heart disease, clinical observation suggests that a digoxin overdose of 6 to 10 mg was the dose that led to death in half of the patients. If more than 10 mg of digoxin were ingested by a child from 1 to 3 years without heart disease, the result would invariably be fatal if antibody fragments were not administered.

After recent administration, either by accident or deliberate self-poisoning, the available load for absorption could be reduced by gastric lavage.

In cases of massive digitalis administration, patients should receive large doses of activated charcoal to prevent absorption and to bind digoxin in the intestine during enteroenteric recirculation.

If hypokalemia exists, it should be corrected with potassium supplements either orally or intravenously, depending on the urgency of the situation. In cases where a large amount of digoxin has been administered, hyperkalemia may occur due to the release of potassium from skeletal muscle. Before administering potassium in cases of digoxin overdose, the serum potassium level should be known.

Bradycardias may respond to atropine, but a temporary cardiac pacemaker may be required. Ventricular arrhythmias may respond to lignocaine (anesthesia medication) or phenytoin (epilepsy treatment medication).

Dialysis is not particularly effective for eliminating digoxin from the body in cases of life-threatening toxicity.

After the intravenous administration of specific digoxin antibody fragments (of ovine origin), there is a rapid reversal of the complications associated with severe digoxin poisoning, digitoxin, and related glycosides.