Label: Information for the User

Digoxina Kern Pharma 0.25 mg/ml Injectable Solution

Digoxina Kern Pharma belongs to the group of medications known as cardiac glycosides. Its active ingredient is digoxin, which increases the force of contraction of the heart muscle by specific inhibition of an enzyme called sodium/potassium-dependent adenosine triphosphatase.+K+

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

• “chronic heart failure” where the main problem is “systolic dysfunction” (alterations in heart contraction),
• when heart failure is accompanied by “atrial fibrillation” (abnormal heart rhythms or frequencies that originate when the upper chambers of the heart (auricles) do not contract uniformly),
• in the treatment of certain “supraventricular arrhythmias” (disorders of heart frequency or rhythm that originate in the auricles), especially atrial flutter (rapid heart rhythm) and atrial fibrillation (abnormal heart rhythms or frequencies that originate when the upper chambers of the heart (auricles) do not contract uniformly), the main benefit being the reduction of ventricular rhythm (slower heart rhythm).

No use Digoxina Kern Pharma

• if you are allergic to digoxin, other digitalis glycosides, or any of the other components of this medication,
• if your doctor has told you that you have any of the following heart problems:
• • intermittent heart block or second-degree atrioventricular block (abnormalities in the transmission of the electrical impulse 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 in the case of Wolff-Parkinson-White syndrome (a hereditary heart disease),
  • ventricular tachycardia (rapid heart rate originating in the ventricles) or in "ventricular fibrillation" (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 intoxication with other cardiac glycosides (heart medications),
• if you know or suspect the existence of an accessory pathway (abnormal electrical communication between the atrium and ventricle) and there are no previous records of supraventricular arrhythmias, this medication is equally contraindicated.

Warnings and precautions

This medication should be used exclusively under the supervision and control of a doctor. Consult your doctor before starting to use this medication 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 medications), or only diuretics, as when they stop administering digoxin, your condition may worsen,
• if you have taken cardiac glycosides (heart medications) two weeks before starting treatment with digoxin, your doctor should consider reducing the initial dosage,
• if you are being administered to elderly patients or patients with reduced renal function, your doctor should consider reducing both the initial and maintenance dosages,
• when you are already being treated with digoxin, your doctor should regularly monitor your serum electrolytes and renal function (concentration of a certain enzyme called serum creatinine). The frequency of controls will depend on the severity of the case,
• if you have severe respiratory disease, as the heart muscle may be more sensitive to digoxin,
• if you have low potassium levels in your blood, as this makes the heart muscle 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), as these increase the sensitivity of the heart muscle to digoxin,
• if you have a thyroid disease, you should exercise caution when using this medication. The initial and maintenance dosages 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 (less activity of this medication) and you may need to increase the dosage. During the treatment of hyperthyroidism, the dosage should be reduced as the disease is controlled,
• patients with malabsorption syndrome (difficulty for the body to absorb nutrients from food) or gastrointestinal reconstructions may require higher dosages of digoxin.

Use of Digoxina Kern Pharma with other medications

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

Agents that cause hypokalemia or intracellular potassium deficiency may increase sensitivity to digoxin; these include some diuretics (medications to facilitate the elimination of liquids), lithium salts, corticosteroids (anti-inflammatory medications), and carbenoxolone (medication for the treatment of mouth sores).

The levels of digoxin in the blood mayincreaseby the concurrent administration of the following medications:

• Amiodarone, flecainide, prazosin, propafenone, quinidine, spironolactone (heart medications).
• Calcium channel blockers and ACE inhibitors (hypertension medications).
• Erythromycin, tetracycline, gentamicin, itraconazole, trimethoprim (antibiotics).
• Quinine (medication for the treatment of malaria).
• Alprazolam, lithium salts (medication for depression).
• Difenoxilate with atropine (association of medications used as anti-diarrheal).
• Indomethacin.
• Propantelina (medication for the treatment of ulcers).

The levels of digoxin in the blood maydecreaseby the concurrent administration of the following medications:

• Antacids.
• Some laxatives.
• Caolín-pectin (anti-diarrheal medication).
• Neomycin, penicillamine, rifampicin (antibiotics).
• Some cytostatics (cancer medications).
• Metoclopramide (medication for the treatment of vomiting).
• Sulfasalazine (anti-inflammatory medication for the stomach).
• Adrenaline (a hormone).
• Salbutamol (medication for the treatment of asthma).
• Colestiramina (medication for the treatment of cholesterol).
• Fenitoin (medication for the treatment of epilepsy).

Pregnancy, lactation, and fertility

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

As with all medications, the use of digoxin during pregnancy should only be considered when the expected clinical benefit of treatment for 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 women or breastfeeding women (see section 2 – "Digoxina Kern Pharma contains ethanol").

Driving and operating machinery

No data are available on how digoxin affects driving or operating machinery, so try not to perform tasks that require special attention until you check how you tolerate the medication.

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

Digoxina Kern Pharma contains ethanol

This medication 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 medication has no notable effects.

Digoxina Kern Pharma contains propylene glycol (E-1520)

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

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

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The digoxin dose for each patient must be established individually according to age, net body weight, and renal function. The suggested doses only aim to serve as an initial guideline.

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

The normal dose is:

Adults and children over 10 years old:

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

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

The loading dose must be administered in divided doses, administering approximately half of the total dose 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 must be administered by intravenous infusion (seeDilution) for 10-20 minutes.

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

• Parenteral loading dose:

Doses in children depend on their weight.

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

The loading dose must be administered in divided doses, administering approximately half of the total dose 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 must be administered by intravenous infusion (seeDilution) for 10-20 minutes.

• Maintenance dose:

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

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 Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forgot to use Digoxina Kern Pharma

Do not use a double dose to compensate for the missed doses.

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

Like all medications, digoxin can produce adverse effects, although not all people will experience them.

Generally, digoxin adverse reactions depend on the dose and occur at higher doses 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 medications administered concurrently.

Cardiac disorders:

Cardiac arrhythmias and alterations in cardiac electrical conduction, including:

• Pre-excitation ventricular contractions that may evolve into bigeminism (an alteration of the heart rhythm in which normal heartbeats alternate with premature beats) or even trigeminism (an alteration of the heart rhythm in which two normal heartbeats alternate with a premature beat).
• Atrial tachycardias (abnormal heart rhythm, such as rapid heartbeats originating in the upper chambers of the heart). They are often accompanied by atrioventricular block (abnormal conduction between the upper and lower chambers of the heart) and the pulse is not always rapid (see section 2).
• Alterations in the electrocardiogram result.
• Sinus bradycardia (a disorder that produces a decrease in the heart rate). It is especially a sign of digoxin intoxication in children.

Gastrointestinal disorders:

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

Oral digoxin administration 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 (breast development in a man) may occur with long-term administration.

Nervous system disorders:

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

Skin and subcutaneous tissue disorders:

Urticarial (hives) or scarlatiform (generalized redness of the skin with small raised lesions) skin eruptions.

Blood and lymphatic system disorders:

Pronounced 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 adverse effects of digoxin in infants and children differ from those observed in adults in several aspects. Although digoxin may produce anorexia, nausea, vomiting, diarrhea, and central nervous system alterations in young patients, these are rarely the initial symptoms of an overdose. Instead, the most common and early manifestation of excessive digoxin dosing in infants and children is the development of cardiac arrhythmias, including sinus bradycardia.

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

Sinus bradycardia may be a sign of impending digoxin intoxication, especially in children, even in the absence of first-degree heart 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 adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospectus.

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

No special storage conditions are required.

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

Medications should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition ofDigoxin Kern Pharma

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

Aspect of the product and content of the package

Injectable solution.

Each package contains 5 ampoules of 2 ml.

Other presentations

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

Holder of the marketing authorization and responsible for manufacturing

Kern Pharma, S.L.

Pol. Ind. Colón II, C/Venus, 72

08228 Terrassa (Barcelona)

Spain

Last review date of this leaflet: April 2020

The detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

This information is intended solely for doctors or healthcare professionals:

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

MODE OF ADMINISTRATION:

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

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

Adults and children over 10 years:

Emergency parenteral loading dose(in patients who have not received cardiac glycosides in the past 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, administering approximately half of the total dose in the first dose and additional fractions of the total dose at intervals of 4 to 8 hours, evaluating clinical response before administering each additional dose. Each dose should be administered by intravenous infusion (seeDilution) for 10-20 minutes.

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

• Emergency parenteral loading dose:

Doses in children depend on their weight.

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

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

• Maintenance:

Your doctor will indicate which is the maintenance dose, depending on the child's response to the 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 reduced and appropriate dose reductions should be considered, above the general posological instructions.

After the newborn phase, children generally require doses proportionally larger 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.

• Loading dose by intravenous routein the above groups:

This should be administered according to the following program:

The loading dose should be administered in divided doses, administering approximately half of the total dose as the first dose and additional fractions of the total dose at intervals of 4 to 8 hours, evaluating clinical response before administering each additional dose. Each dose should be administered by intravenous infusion (seeDilution) 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 dose schemes are designed to be a guideline, and a careful clinical observation and control of digoxin serum levels (seeControl) should be performed to adjust the dose in these pediatric patient groups.

If cardiac glycosides have been administered in the past two weeks before starting treatment with this medication, the optimal loading doses of digoxin should be lower than those recommended above.

Cardiac glycosides are an important cause of accidental poisoning in children. The tolerance of newborns to cardiac glycosides is variable since the renal clearance of the medication is reduced. Premature and immature newborns are especially sensitive.

Older patients:

The tendency to alter renal function and the low net body weight in older patients affect the pharmacokinetics of digoxin, making it easy to appear with elevated serum digoxin levels and associated toxicity, unless lower doses of digoxin are used than those used in non-elderly patients. Serum digoxin levels should be regularly monitored, and hypokalemia should be avoided.

Recommendations for Doses in Specific Patient Groups:

See "Warnings and Precautions" section.

Dilution of Digoxin Kern Pharma:

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

It is known that this medication, when diluted in a ratio of 1 to 250 (for example, a 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):

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

The dilution should be performed in 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.

Digoxin serum concentration 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 if a patient's symptoms are due to digoxin, the clinical status, 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 when values do not appear to be in agreement 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 that led to death in half of the patients. If an adult without heart disease ingested more than 25 mg of digoxin, death or progressive toxicity would occur, which would only respond to the administration of specific fragments of antibodies that bind to 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 that led to death in half of the patients. If more than 10 mg of digoxin were ingested by a child aged 1 to 3 years without heart disease, the result would be invariably fatal unless fragments of antibodies were 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 digital administration, patients should receive large doses of activated charcoal to prevent absorption and to bind to digoxin in the intestine during enterohepatic 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 appear 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 pacemaker may be required. Ventricular arrhythmias may respond to lignocaine (anesthetic medication) or phenytoin (epilepsy medication).

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

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