Digoxin Kern Pharma 0.25 mg/ml solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

Digoxin Kern Pharma 0.25 mg/ml solution for injection

Package leaflet:

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

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

Digoxina Kern Pharma belongs to a group of medicines known as cardiotonic glycosides. Its active substance is digoxin, which increases the force of contraction of the heart muscle by specifically inhibiting an enzyme called sodium-potassium adenosine triphosphatase (Na+/K+ ATPase).

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

• Chronic heart failure where the main problem is systolic dysfunction (impaired contraction of the heart),
• when heart failure is accompanied by atrial fibrillation (abnormal heart rhythm or rate originating from irregular contractions of the upper chambers of the heart (atria)),
• in the treatment of certain supraventricular arrhythmias (disorders of heart rate or rhythm originating in the atria), particularly atrial flutter (rapid heartbeat) and atrial fibrillation (abnormal heart rhythm or rate originating from irregular contractions of the upper chambers of the heart (atria)), with the main benefit being reduction of ventricular rate (slower heart rate).

2. What you need to know before starting to use Digoxin Kern Pharma

Do not use Digoxin Kern Pharma

• if you are allergic to digoxin, to other digitalis glycosides, or to any of the other ingredients of this medicine,
• if you have been told you have any of the following heart problems:
  • intermittent heart block or second-degree atrioventricular block (abnormalities in the transmission of electrical impulses between the upper and lower chambers of the heart), especially if you have a history of a heart condition called Stokes-Adams syndrome,
  • certain types of "supraventricular arrhythmias", such as Wolff-Parkinson-White syndrome (a hereditary heart disease),
  • "ventricular tachycardia" (a fast heartbeat originating in the ventricles) or "ventricular fibrillation" (a very abnormal heart rhythm (arrhythmia) that may be life-threatening),
  • "hypertrophic obstructive cardiomyopathy" (a disease characterized by excessive growth of heart muscle),
• if you have arrhythmias caused by intoxication with other cardiac glycosides (heart medications),
• if an accessory pathway (an abnormal electrical connection from atrium to ventricle) is known or suspected 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 (heart attack), digoxin should be used with caution,
• if you are being treated with diuretics and an ACE inhibitor (medications for heart disease and high blood pressure), or with diuretics alone, as discontinuation of digoxin may worsen your condition,
• if you have taken cardiac glycosides (heart medications) within the two weeks prior to starting digoxin treatment, your doctor should consider reducing the initial dose,
• if you are elderly or have impaired kidney function, your doctor should consider reducing both the initial and maintenance doses,
• once you are already on digoxin treatment, your doctor should periodically monitor your serum electrolytes and kidney function (serum creatinine enzyme concentration). The frequency of monitoring will depend on the severity of your condition,
• if you have severe respiratory disease, as the myocardium (heart muscle) may be more sensitive to digoxine,
• if you have low potassium levels in the blood, as this increases the sensitivity of the myocardium (heart muscle) to digoxin,
• if you have hypoxia (low blood oxygen levels), hypomagnesemia (low blood magnesium levels), or marked hypercalcemia (high blood calcium levels), as these conditions increase myocardial (heart muscle) sensitivity to digoxin,
• if you have thyroid disease, you should use this medicine with caution. The initial and maintenance doses of digoxin should be reduced when thyroid function is low. In cases of hyperthyroidism (high levels of thyroid hormone in the blood), there is relative resistance to digoxin (reduced drug activity), and the dose may need to be increased. During treatment of thyrotoxicosis (excess thyroid hormones), the dose should be reduced as the disease is brought under control,
• patients with malabsorption syndrome (difficulty in absorbing vitamins, minerals, and other nutrients from food) or gastrointestinal reconstructions may require higher doses of digoxin.

Use of Digoxin Kern Pharma with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Agents that cause hypokalemia or intracellular potassium deficiency may increase sensitivity to Digoxin; these include certain diuretics (medicines to promote fluid elimination), lithium salts, corticosteroids (anti-inflammatory medicines), and carbenoxolone (a medicine used to treat mouth ulcers).

Blood levels of digoxin may increase when taken together with the following medicines:

• Amiodarone, flecainide, prazosin, propafenone, quinidine, spironolactone (medicines for heart conditions).
• Calcium channel blockers and ACE inhibitors (medicines for high blood pressure).
• Erythromycin, tetracycline, gentamicin, itraconazole, trimethoprim (antibiotics).
• Quinine (a medicine used to treat malaria).
• Alprazolam, lithium salts (a medicine for depression).
• Diphenoxylate with atropine (a combination medicine used as an antidiarrheal).
• Indomethacin.
• Propantheline (a medicine used to treat ulcers).

Blood levels of digoxin may decrease when taken together with the following medicines:

• Antacids.
• Some laxatives.
• Kaolin-pectin (an antidiarrheal medicine).
• Neomycin, penicillamine, rifampicin (antibiotics).
• Some cytostatic agents (medicines for cancer treatment).
• Metoclopramide (a medicine used to treat vomiting).
• Sulfasalazine (an anti-inflammatory stomach medicine).
• Adrenaline (a hormone).
• Salbutamol (a medicine used to treat asthma).
• Cholestyramine (a medicine used to treat high cholesterol).
• Phenytoin (a medicine used to treat epilepsy).

Inform your doctor if you are taking a medicine containing enzalutamide (used to treat prostate cancer). It may interfere with your digoxin tests.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist 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.

Digoxin injectable solution contains ethanol, which should be taken into account in pregnant or breastfeeding women (see section 2 – “Digoxin Kern Pharma contains ethanol”).

Driving and using machines

There are no data available on how digoxin affects the ability to drive or operate machinery. Therefore, avoid performing tasks requiring special attention until you know how you tolerate the medicine.

The propylene glycol contained in this medicine may produce effects similar to those of alcohol consumption and may increase the likelihood of these adverse effects. This may reduce your ability to drive or operate machinery.

Digoxin 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 has no significant effects.

Digoxin Kern Pharma contains propylene glycol (E-1520)

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

Use this medicine only as prescribed by your doctor. Your doctor may perform additional monitoring while you are taking this medicine.

3. How to use Digoxin Kern Pharma

Follow exactly the administration instructions for this medicine given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

The digoxin dose for each patient must be individually determined based on age, lean body weight, and renal function. The suggested doses are intended only as an initial guide.

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

The usual dose is:

Adults and children over 10 years of age:

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

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

The loading dose should be administered in divided doses, with approximately half of the total dose given initially, followed by additional fractions of the total dose at intervals of 4 to 8 hours, assessing 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 of age (if they have not received cardiac glycosides in the preceding two weeks):

• Emergency parenteral loading dose:

Doses in children depend on their weight.

However, these doses range 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 initially, followed by additional fractions of the total dose at intervals of 4 to 8 hours, assessing 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 determine the maintenance dose based on the child's response to the initial treatment with this medicine.

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

If you use more Digoxin Kern Pharma than you should

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

If you forget to use Digoxin Kern Pharma

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

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

4. Possible adverse effects

Like all medicines, digoxin can cause adverse effects, although not everyone experiences 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 serum concentration range, and when careful attention is paid to concomitant conditions and medications.

Cardiac disorders:

Cardiac arrhythmias and disturbances in the heart's electrical conduction, including:

• Ventricular contractions occurring earlier than the heart's normal rhythm, which may progress to bigeminy (a cardiac rhythm disorder in which normal heartbeats alternate with premature beats) or even trigeminy (a cardiac rhythm disorder in which two normal heartbeats alternate with one premature beat).
• Atrial tachycardias (a heart rhythm disorder (pulse), such as excessively rapid heartbeats originating in the upper chambers of the heart). These are often accompanied by atrioventricular block (a disorder in electrical conduction between the atria (upper chambers) and ventricles (lower chambers) of the heart), and the pulse is not always rapid (see section 2.).
• Changes in electrocardiogram (ECG) findings.
• Sinus bradycardia (a disorder causing a reduced heart rate). Particularly in children, this may be a sign of digoxin toxicity.

Gastrointestinal disorders:

Anorexia, nausea, and vomiting that resolve within a few hours after taking the medicine. Diarrhea may also occur.

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

Reproductive system and breast disorders:

Gynecomastia (breast development in males) may occur with long-term administration.

Nervous system disorders:

Weakness, apathy, fatigue, malaise, headache, visual disturbances, depression, and even psychosis have been reported.

Skin and subcutaneous tissue disorders:

Skin rashes of urticarial type (red, itchy skin welts) or scarlatiniform type (generalized skin redness with small raised lesions).

Blood and lymphatic system disorders:

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

Thrombocytopenia (decreased number of platelets in the blood).

Paediatric population

The side effects of digoxin in infants and children differ from those observed in adults in several aspects. Although digoxin may cause anorexia, nausea, vomiting, diarrhea, and central nervous system (CNS) disturbances in young patients, these are rarely the initial symptoms of overdose. Instead, the earliest and most frequent manifestation of excessive digoxin dosing in infants and children is the development of cardiac arrhythmias, including sinus bradycardia.

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

Sinus bradycardia may be a sign of impending digoxin toxicity, especially in children, even in the absence of first-degree heart block. Any arrhythmia or disturbance in cardiac conduction that develops in a child taking digoxin should be assumed to be caused by digoxin until further evaluation proves otherwise.

If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet.

5. Storage of Digoxin 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 stated on the packaging after "EXP". The expiry date refers to the last day of the indicated month.

Medicines must not be disposed of via wastewater or household waste. Dispose of unused medicines and their containers at a SIGRE collection point at your pharmacy. If you are unsure, ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information

Composition of Digoxina Kern Pharma

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

Appearance of the medicinal product and contents of the pack

Injectable solution.

Each pack contains 5 ampoules of 2 ml.

Other presentations

• Digoxina Kern Pharma 0.25 mg tablets. Packs containing 50 tablets.
• Digoxina 0.05 mg/ml pediatric oral solution marketed under the name Lanacordin Pediátrico. 60 ml bottle supplied 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 latest review of this leaflet: August 2025

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

This information is intended for healthcare professionals only:

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

DIRECTIONS FOR USE:

Intramuscular administration is painful and associated with muscle necrosis (death of cardiac muscle cells). This route is not recommended.

Rapid intravenous injection may cause vasoconstriction leading to hypertension and/or reduced coronary flow. Therefore, slow injection rate is important in hypertensive heart failure and acute myocardial infarction.

Adults and children over 10 years of age:

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

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

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 administered at intervals of 4 to 8 hours, assessing clinical response before each additional dose. Each dose must be administered by intravenous infusion (see Dilution) over 10–20 minutes.

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

• Emergency parenteral loading dose:

Doses in children depend on body weight.

However, these doses range 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 administered at intervals of 4 to 8 hours, assessing clinical response before each additional dose. Each dose must be administered by intravenous infusion (see Dilution) over 10–20 minutes.

• Maintenance:

Your doctor will determine the maintenance dose based on the child's response to initial digoxin treatment.

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

In newborns, especially premature infants, renal clearance of digoxin is reduced, and appropriate dose reductions should be considered beyond general dosing guidelines.

After the newborn period, children generally require proportionally higher doses than adults relative to body weight or body surface area, as shown in the table below. Children over 10 years of age require adult doses proportional to their body weight.

• Intravenous loading dose in the above groups:

This should be administered according to the following regimen:

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

• Maintenance:

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

Preterm newborns:

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

Term newborns and children up to 10 years of age:

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

These dosing regimens are intended as guidelines, and careful clinical observation and monitoring of serum digoxin levels (see Monitoring) are required to adjust the dose in these pediatric patient groups.

If cardiac glycosides have been administered within the two weeks preceding the initiation of treatment with this medicinal product, lower optimal loading doses of digoxin than those recommended above should be anticipated.

Cardiac glycosides are a significant cause of accidental poisoning in children. Newborns’ tolerance to cardiac glycosides is variable due to reduced renal clearance of the drug. Premature and immature newborns are particularly sensitive.

Elderly Patients:

The tendency toward impaired renal function and reduced lean body mass in elderly patients influences the pharmacokinetics of digoxin such that elevated serum digoxin levels and associated toxicity may easily occur unless lower digoxin doses are used than those used in younger patients. Serum digoxin levels should be monitored regularly, and hypokalemia should be avoided.

Dose Recommendations in Specific Patient Groups:

See section “Warnings and precautions”.

Dilution of Digoxina Kern Pharma:

This medicinal product may be administered undiluted or diluted with a volume of diluent at least four times greater. Using a volume of diluent less than four times the volume of the product may lead to precipitation of digoxin.

It is known that when this medicinal product is diluted at a ratio of 1 to 250 (e.g., one 2 ml ampoule containing 500 micrograms added to 500 ml of infusion solution), it is compatible with the following infusion solutions and remains stable for up to 48 hours at room temperature (20 to 25°C):

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

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

Monitoring:

Serum digoxin concentrations may 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.

Serum digoxin concentration can be determined by radioimmunoassay. Blood should be drawn at least 6 hours or more after the last dose of this medicinal product. There are no strict guidelines regarding the serum concentration range that is most effective, but most patients benefit with minimal risk of developing signs and symptoms of toxicity when digoxin concentrations are between 0.8 ng/ml (1.02 nmol/l) and 2.0 ng/ml (2.56 nmol/l). Above this range, signs and symptoms of toxicity may become more frequent, and levels above 3.0 ng/ml (3.84 nmol/l) are very likely to be toxic. However, when determining whether a patient's symptoms are due to digoxin, clinical status along with serum potassium levels and thyroid function are important factors to consider.

Other glycosides, including digoxin metabolites, may interfere with available assays; therefore, caution should be exercised with values that do not appear consistent with the patient's clinical status.

SYMPTOMS OF OVERDOSE AND TREATMENT:

Adults:

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

Children:

In children aged 1 to 3 years without heart disease, clinical observation suggests that a digoxin overdose of 6 to 10 mg was the dose lethal to half of patients. If more than 10 mg of digoxin were ingested by a child aged 1 to 3 years without heart disease, the outcome would be invariably fatal unless antibody fragments were administered.

After recent accidental or deliberate self-poisoning, the amount available for absorption may be reduced by gastric lavage.

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

If hypokalemia is present, 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 release of potassium from skeletal muscle. Serum potassium levels must be known before administering potassium in cases of digoxin overdose.

Bradycardias may respond to atropine, but temporary cardiac pacing may be required. Ventricular arrhythmias may respond to lignocaine (anesthetic medication) or phenytoin (antiepileptic medication).

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

Following intravenous administration of specific digoxin antibody fragments (ovine origin), a rapid reversal of complications associated with severe poisoning by digoxin, digitoxin, and related glycosides occurs.