Package Insert: Information for the User

Lanacordin Pediatric 0.05 mg/ml Oral Solution

Digoxin

Read this entire package insert carefully before starting to use the medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert.

Lanacordin Pediátrico 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+

Lanacordin Pediátrico 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 Lanacordin Pediátrico

• if you are allergic (hypersensitive) to digoxin, to other digitalis glycosides, or to any of the other components of Lanacordin Pediátrico,
• if your doctor has told you that you have any of the following heart problems:
• • intermittent heart block or second-degree atrioventricular block (alterations 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 disease called Stokes-Adams syndrome,
  • a certain type of "supraventricular arrhythmias", such as in the case of Wolff-Parkinson-White syndrome (a hereditary heart disease),
  • "ventricular tachycardia" (rapid heart rate that originates in the ventricles) or in "ventricular fibrillation" (very abnormal heart rhythm (arrhythmia) 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, Lanacordin Pediátrico is equally contraindicated.

Warnings and Precautions

This medication should be used exclusively under the supervision and control of a doctor. Consult your doctor before using this medication in any of the following cases:

• if you have recently had a myocardial infarction, digoxin should be taken with caution, although it is not contraindicated in the immediate period after the infarction,
• if you are being treated with diuretics and an ACE inhibitor (heart and hypertension medications), or only diuretics, as when they stop administering digoxin, it could lead to a worsening of your disease,
• 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 administered to elderly patients or in patients with decreased renal function, the doctor should think about reducing both the initial and maintenance doses.
• when you are already being treated with digoxin, your doctor should periodically monitor your serum electrolytes and renal function (concentration of an enzyme called serum creatinine). The frequency of the 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 the 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 thyroid disease, you should exercise caution when using Lanacordin Pediátrico. The initial and maintenance doses of Lanacordin Pediátrico 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 dose. During the treatment of thyrotoxicosis (excess of thyroid hormones), the dose should be reduced as the disease is controlled.
• patients with malabsorption syndrome (difficulty of the body to absorb correctly the vitamins, minerals, and other nutrients that come from food) or gastrointestinal reconstructions may require higher doses of digoxin.

Use of Lanacordin Pediátrico with other medications

Inform your doctor or pharmacist if you are using or have recently used other medications, even those purchased without a prescription.

The levels of digoxin in the blood may increase with the concurrent administration of the following medications:

• Amiodarone, flecainide, prazosin, propafenone, quinidine, spironolactone (heart medications).
• Diuretics (medications to facilitate the elimination of liquids).
• 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).
• Difenoxin with atropine (association of medications used as anti-diarrheal).
• Indomethacin, corticosteroids (anti-inflammatory medications).
• Propantelina (medication for the treatment of ulcers).
• Carbenoxolone (medication for the treatment of mouth sores).

The levels of digoxin in the blood may decrease with the concurrent administration of the following medications:

• Antacids.
• Some laxatives.
• Caolín-pectina (anti-diarrheal medication).
• Neomycin, penicillamine, rifampicin (antibiotics).
• Some cytostatics (cancer medications).
• Metoclopramide (medication for the treatment of vomiting).
• Sulfasalazine (anti-inflammatory medication of 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 and lactation

Consult your doctor or pharmacist before using any medication.

Digoxin is not contraindicated in pregnancy, although, as with all medications, its use 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, and breastfeeding is not contraindicated.

Driving and operating machinery

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

Lanacordin Pediátrico contains saccharose

This medication contains saccharose. If your doctor has told you that you have an intolerance to certain sugars, consult with him before taking this medication.

Patients with diabetes mellitus should note that this medication contains 0.16 g of glucose per ml. It may cause tooth decay.

Lanacordin Pediátrico contains ethanol (alcohol)

This medication contains 10% ethanol (alcohol), which corresponds to 0.1 mg per ml, equivalent to 2 ml of beer and 0.8 ml of wine.

This medication is harmful to people with alcoholism.

The alcohol content should be taken into account in the case of pregnant women or breastfeeding women, children, and high-risk groups, such as patients with liver disease or epilepsy.

Lanacordin Pediátrico contains tartrazine

This medication may cause allergic reactions because it contains Tartrazine (E-102). It may cause asthma, especially in patients allergic to acetylsalicylic acid.

Follow exactly the administration instructions for Lanacordin Pediátrico as indicated by your doctor. Consult your doctor or pharmacist if you have any doubts.

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

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

Lanacordin Pediátrico is supplied with a graduated pipette that must be used to measure all doses.

The normal dose is:

Adults and children over 10 years old:

Initial dose (loading dose):

• Fast oral administration:

750 to 1500 micrograms (0.75 to 1.5 mg) as a single dose.

• Slow oral administration:

250 to 750 micrograms (0.25 to 0.75 mg) should be administered daily for 1 week.

Maintenance dose:

Your doctor will indicate your maintenance dose, depending on your response to the initial treatment with Lanacordin Pediátrico.

On average, most patients will be maintained on 125 to 750 micrograms (0.125 to 0.75 mg) of digoxin per day. However, in those who show greater sensitivity to digoxin adverse reactions, a dose of 62.5 micrograms (0.0625 mg) per day or less may be sufficient.

Newborns, infants, and children under 10 years old (if they have not received cardiac glycosides in the preceding 2 weeks):

• Initial dose by oral administration:

Doses in children depend on their weight.

However, these doses range from 25 to 45 micrograms over 24 hours.

The initial 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, with clinical response evaluated before each additional dose.

• Maintenance dose:

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

On average, most patients will be maintained at 20% to 25% of the initial dose, administered every 24 hours.

If you use more Lanacordin Pediátrico than you should:

If you have used Lanacordin Pediatrico more than you should, consult your doctor, pharmacist, or call the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount taken.

If you forgot to use Lanacordin Pediátrico:

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

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

Like all medications, Lanacordin Pediatric can produce adverse effects, although not everyone 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 medication administered concurrently.

Cardiac disorders:

Cardiac arrhythmias and alterations in heart conduction, including:

• Pre-excitation ventricular contractions that may evolve into bigeminism (a heart rhythm alteration in which normal heartbeats alternate with premature beats) or even trigeminism (a heart rhythm alteration in which two normal heartbeats alternate with a premature beat).
• Atrial tachycardias (a heart rhythm disorder characterized by rapid heartbeats originating in the upper chambers of the heart). They are often accompanied by atrioventricular block (a conduction disorder between the upper and lower chambers of the heart) and the pulse is not always rapid (see section 2. What you need to know before using Lanacordin Pediatric).
• Alterations in the electrocardiogram result.
• Sinus bradycardia (a disorder that produces a decrease in heart rate). In children, it may be a sign of digoxin intoxication.
• In children, digoxin use can produce any type of arrhythmia. The most common are conduction alterations or supraventricular tachyarrhythmias (heart rhythm disorders not originating in the ventricles).

Gastrointestinal disorders:

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

Oral digoxin 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)

If you experience adverse effects, consult your doctor or pharmacist, even if they do not appear in this prospectus.

Keep out of sight and reach of children.

Store below 30°C.

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

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

Composition of Lanacordin Pediatric

• The active ingredient is digoxin. Lanacordin Pediatric contains 0.05 mg of digoxin per ml of solution.
• The other components are sucrose, ethanol, tartrazine, anhydrous sodium phosphate, citric acid, methyl hydroxybenzoate, lime essential oil, propylene glycol, and purified water.

Appearance of the product and contents of the package

Oral solution. Package of 60 ml provided with a dosing syringe.

Holder of the marketing authorization and responsible for manufacturing

Kern Pharma, S.L.

Polígono Ind. Colón II

Venus, 72

08228 Terrassa (Barcelona)

Spain

Last review date of this leaflet: November 2021

The detailed and updated information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (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.

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 heart failure with hypertension and acute myocardial infarction.

Adults and children over 10 years:

Initial dose (loading dose):

• Fast oral administration:

750 to 1500 micrograms (0.75 to 1.5 mg) as a single dose.

In less urgent cases, or when there is a higher risk of toxicity, for example in elderly patients, the initial oral dose should be administered in divided doses every 6 hours, administering approximately half of the total dose in the first dose. The clinical response should be evaluated before administering each additional dose (see section 2 "What you need to know before starting to use...").

• Slow oral administration:

250 to 750 micrograms (0.25 to 0.75 mg) should be administered daily for 1 week, followed by an appropriate maintenance dose. Clinical response should be observed within a week.

NOTE: The choice between a slow or fast oral digitalization protocol will depend on the patient's clinical condition and the urgency of the clinical indication.

Maintenance dose:

Your doctor will indicate your maintenance dose, depending on your response to the initial treatment with Lanacordin Pediatric.

On average, most patients will be maintained on 125 to 750 micrograms (0.125 to 0.75 mg) of digoxin per day. However, in those who show greater sensitivity to digoxin side effects, a dose of 62.5 micrograms (0.0625 mg) per day or less may be sufficient.

The maintenance dose should be based on the percentage of body reserves lost daily through elimination. The following formula has had extensive clinical use:

Maintenance dose = Maximum body reserves xdaily loss (percentage)

100

Where:

• Maximum body reserves = loading dose

Daily loss (percentage) = 14 + creatinine clearance (Ccr) / 5

• Ccr is the creatinine clearance corrected for a body weight of 70 kg or 1.73 m2of body surface area. If only serum creatinine concentrations are available, an estimated Ccr (corrected for a body weight of 70 kg) in men is:

Ccr =(140 - age)

Scr (in mg/100 ml)

NOTE: When serum creatinine values are obtained in micromol/l, these can be converted to mg/100 ml (mg%) as indicated below:

Scr (mg/100 ml)= Scr (micromol/l) x 113.12

10,000

=Scr (micromol/l)

88.4

• Where 113.12 is the molecular weight of creatinine.
• In women, this result should be multiplied by 0.85.
• These formulas cannot be used for creatinine clearance in children.

In practice, most patients will be maintained on 125 to 750 micrograms (0.125 to 0.75 mg) of digoxin per day. However, in those who show greater sensitivity to digoxin side effects, a dose of 62.5 micrograms (0.0625 mg) per day or less may be sufficient.

Newborns, infants, and children under 10 years (if they have not received cardiac glycosides in the past 2 weeks):

• Loading dose by oral administration:

Doses in children depend on their weight.

However, these doses range from 25 to 45 micrograms per 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 the clinical response before administering each additional dose.

• Maintenance:

Your doctor will indicate your maintenance dose, depending on your response to the initial treatment with Lanacordin Pediatric.

On average, most patients will be maintained on 20% to 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, above general dosing instructions.

After the newborn phase, children generally require doses proportionally greater 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 oral administration:

This should be administered according to the following program:

Newborns premature <1.5 kg25 micrograms/kg per 24 hours.

Newborns premature 1.5 kg - 2.5 kg30 micrograms/kg per 24 hours.

Newborns at term up to 2 years45 micrograms/kg per 24 hours.

2 to 5 years35 micrograms/kg per 24 hours.

5 to 10 years25 micrograms/kg per 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 the clinical response before administering each additional dose.

• Maintenance:

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

Newborns premature:

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

Newborns at term 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 control of serum digoxin levels (see Control) should be performed to adjust the dose in these pediatric patient groups.

If cardiac glycosides have been administered in the past 2 weeks before starting treatment with Lanacordin Pediatric, the optimal loading doses of Lanacordin will 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 renal clearance of the medication is reduced. Premature and immature newborns are especially sensitive.

Older adults:

The tendency to alter renal function and the low net body mass in older adults affects the pharmacokinetics of Lanacordin Pediatric in such a way that elevated serum digoxin levels and associated toxicity can easily occur, unless lower doses of Lanacordin are used than those used in non-elderly patients. Serum digoxin levels should be regularly monitored, and hypokalemia should be avoided.

Recommendations for Dosage in Specific Patient Groups:

See "Warnings and precautions" section.

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 Lanacordin Pediatric. 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, 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 consistent with the patient's clinical condition.

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 outcome would be invariably fatal if fragments of antibodies were not administered.

After recent ingestion, either accidentally or intentionally, the amount available for absorption could be reduced by gastric lavage.

Patients who have ingested a large amount of digitalis 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 Lanacordin Pediatric has been ingested, 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 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), rapid reversal of complications associated with severe digoxin poisoning occurs.