LANIRAPID 0.1 mg TABLETS

Introduction

Package Leaflet: Information for the User

Lanirapid 0.1 mg tablets

β-Methyldigoxin

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

1. What is Lanirapid and what is it used for
2. What you need to know before you take Lanirapid
3. How to take Lanirapid
4. Possible side effects
5. Storage of Lanirapid
6. Contents of the pack and other information

1. What is Lanirapid and what is it used for

Lanirapid belongs to a group of medicines called cardiac glycosides (digitalis). Its active substance is β-Methyldigoxin, which acts on heart cells by increasing the strength and speed of contraction, delaying the conduction of the stimulus, and increasing the ventricular stimulus response.

This medicine is indicated for the treatment of:

• Congestive heart failure (when the heart does not pump enough blood and fluid accumulates in the lungs).
• Cardiac rhythm disorders (heart rhythm): atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia (problems with the speed and rhythm of heartbeats).

2. What you need to know before you take Lanirapid

Do not take Lanirapid

• if you are allergic to β-Methyldigoxin or any of the other components of this medicine (listed in section 6);
• if you have carotid sinus syndrome (sudden episodes of dizziness and loss of consciousness) and thoracic aortic aneurysm (dilation of the aorta at the level of the thorax);
• if you have hypertrophic obstructive cardiomyopathy (a type of heart disorder);
• if you have Wolff-Parkinson-White syndrome (a type of heart disease) or any other evidence of an accessory pathway;
• if you have tachycardia (fast or irregular heart rhythm) or ventricular fibrillation (very abnormal heart rhythm that can be fatal).

Warnings and precautions

Consult your doctor or pharmacist before starting to take this medicine in any of the following cases:

• If you have taken another digitalis medicine during the 2 weeks prior to using this medicine, as your doctor will consider reducing the initial dose.
• If you have hypokalemia (low potassium levels in the blood), as it could increase the action of this medicine. It should be kept in mind the need to monitor potassium levels in the blood, especially when using diuretic medicines at the same time.
• If you have hypomagnesemia (low magnesium levels in the blood), as it could increase the action of this medicine, and it may be necessary to reduce the dose.
• If you have hypercalcemia (high calcium levels in the blood), as it could increase the action of this medicine, and it may be necessary to reduce the dose.
• If you have hypoxia (lack of oxygen in the body's tissues), as it could increase the action of this medicine, and it may be necessary to reduce the dose.
• If you have thyroid gland function disorders: In the case of hypothyroidism (decreased production of thyroid hormones), the action of this medicine may increase, and it may be necessary to reduce the dose. On the other hand, in the case of hyperthyroidism (increased production of thyroid hormones), higher doses of β-Methyldigoxin may be required. In these patients, it will also be taken into account that any modification in the state of thyroid gland function may affect the response to the established dose (see section 3).
• If you have recently had a myocardial infarction (heart attack), have advanced respiratory failure (decreased respiratory function), or have rheumatic carditis (inflammation of the heart), as it usually increases sensitivity to digitalis. In these cases, the dose will be adjusted with due precautions.
• If you have kidney failure, as it can cause accumulation of the medicine, and the dose should be adjusted according to the degree of failure (see section 3).
• If you take natural products or plant extracts that contain Hypericum perforatum, as it could decrease the effect of this medicine.

You should be well aware that heart rhythm disorders caused by an increase in digitalis dose are very similar to certain clinical conditions where digitalis is indicated. The medicine will be used with maximum caution in cases where it cannot be totally excluded that the condition being treated is caused by digitalis intoxication.

Similarly, it is recommended to have special precautions in case of alterations in the formation or conduction of the stimulus with bradycardia, as well as before cardioversion. It will be used in case of absolute necessity and with maximum precautions in case of complete conduction block (AV block grades II and III), Adams-Stokes syndrome, subaortic stenosis, or glomerular kidney disease (glomerulonephritis).

Children and adolescents

Sensitivity to β-Methyldigoxin may increase in the pediatric population (children and adolescents).

Taking Lanirapid with other medicines

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

The combination of this medicine with other medicines can cause an increase or decrease in the effects of β-Methyldigoxin.

The medicines that can increase the action of β-Methyldigoxin are:

• Calcium
• Diuretics and laxatives
• Penicillins (antibiotic medicines)
• Amphotericin B (a medicine that prevents the growth of certain fungi)
• Carbenoxolone (a medicine used to relieve ulcers)
• Corticosteroid medicines
• ACTH (a type of hormone)
• Salicylates (a type of medicine that relieves pain and reduces fever)
• Verapamil, diltiazem, and captopril (medicines used to treat hypertension)
• Antiarrhythmic medicines (heart medicines), such as quinidine, amiodarone, procainamide, and propafenone
• Tetracyclines and erythromycin (antibiotic medicines)
• Reserpine and Rauwolfia alkaloids (medicines for the treatment of hypertension)
• Beta-blocker agents (heart medicines)
• Suxamethonium chloride, pancuronium, succinylcholine (muscle relaxants)
• Tricyclic antidepressants (medicines for depression)
• Sympathomimetic substances (such as ephedrine and adrenergic agents)
• Theophylline (a medicine to facilitate breathing)
• Epinephrine (heart stimulant)
• Medicines for the thyroid gland

The medicines that can decrease the action of β-Methyldigoxin are:

• Potassium ions
• Antidiarrheal medicines of the intestinal absorbent type (such as activated charcoal or pectins)
• Ion exchange resins (such as cholestyramine, colestipol)
• Antacids
• Neomycin, para-aminosalicylic acid (antibiotic medicines)
• Cytostatic medicines (medicines to treat cancer)
• Phenytoin (a medicine used to treat epilepsy).

Similarly, special attention should be paid if this medicine is combined with medicines that increase heart function or with medicines that induce hypokalemia and hypomagnesemia.

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 taking this medicine.

Pregnancy:

Your doctor will decide whether you can take this medicine during pregnancy, as it should only be used if the expected benefit to the mother outweighs the possible risk to the fetus.

Breastfeeding:

β-Methyldigoxin is excreted in breast milk.

This medicine should only be used when strictly necessary, under medical supervision, and the heart rate of breastfed infants should be monitored.

Driving and using machines

No data are available on how β-Methyldigoxin affects the ability to drive or use machines. Therefore, do not perform tasks that require special attention until you know how you tolerate the medicine.

Lanirapid contains lactose

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Lanirapid

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

Both the initial dose and the maintenance dose must be established individually for each patient, according to the plasma concentration.

The dose depends on the needs of cardiac glycosides and the elimination rate. The necessary amount will change if you have thyroid gland function disorders, have kidney failure, or are an elderly person (see "Use in special populations").

As a maintenance dose, most patients need 2 to 3 tablets per day (i.e., between 0.2 and 0.3 mg of β-methyldigoxin per day). In isolated cases, 1 tablet per day (0.1 mg of β-methyldigoxin per day) is sufficient. Only in patients with high glycoside needs is a daily maintenance dose of 0.4 mg of β-methyldigoxin (4 tablets per day) indicated.

The following table can serve as a guide for both initial and maintenance treatment with doses of 2 and 3 tablets per day (i.e., 0.2 and 0.3 mg of β-methyldigoxin per day):

In cases of severe heart failure (severe heart failure) and according to glycoside needs, your doctor may consider it appropriate to perform a faster initial treatment. For example, and for guidance, an administration of 0.6 mg of β-methyldigoxin per day (i.e., 2 Lanirapid tablets 3 times a day) for 2 to 4 days would be equivalent to a maintenance dose of 2 to 4 tablets per day.

Method of administration

The tablets should be swallowed without chewing, preferably after meals and with a little liquid.

The tablet can be divided into equal doses.

Use in special populations

Patients with kidney failure:

In patients with renal insufficiency, the dose of methyldigoxin should be adjusted according to creatinine clearance.

Elderly patients:

In elderly patients, the dose of methyldigoxin should be adapted according to renal function. The decrease in renal function in this group of patients should be determined by calculating creatinine clearance.

Patients with thyroid gland function disorders:

In patients with hypothyroidism, it may be necessary to reduce the dose of methyldigoxin. On the other hand, patients with hyperthyroidism may require higher doses of methyldigoxin, depending on the serum concentration of thyroid hormones.

Use in children and adolescents

There is no specific recommendation for the use of this medicine in the pediatric population. There are no data on the dose in the pediatric population, so its use is not recommended in this population.

If you take more Lanirapid 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 taken.

If you forget to take Lanirapid

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

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

4. Possible side effects

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

Most of the side effects attributed to digitalis are manifestations of overdose.

Blood and lymphatic system disorders

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

Immune system disorders

Immunological reactions (such as lupus erythematosus) and eosinophilia.

Metabolism and nutrition disorders

Anorexia

Nervous system disorders

Central nervous system alterations (such as headaches, facial pain, dizziness, fatigue, somnolence, insomnia, psychic alterations, disorientation, depression, apathy, hallucinations, delirium, and acute psychosis).

Eye disorders

Visual disturbances (colored or halo vision, yellow vision, blurred vision, decreased visual acuity, or double vision).

Cardiac disorders

Bradycardia and arrhythmias, tachycardia, and AV block grade II and III.

In case of overdose with β-methyldigoxin, cardiac arrhythmias (heart rhythm disorders) can increase to the point of producing life-threatening cardiac rhythm disorders in the case of severe intoxication.

Gastrointestinal disorders

Hypersalivation, loss of appetite, diarrhea, nausea, vomiting, abdominal pain, mesenteric infarction.

Skin and subcutaneous tissue disorders

Allergic reactions (such as erythema).

Musculoskeletal and connective tissue disorders

Muscle weakness.

Reproductive system and breast disorders

Gynecomastia (enlargement of male breasts).

Other side effects in children and adolescents

Cardiac arrhythmias are usually the first symptom of overdose in children and are mainly of nodal or atrial origin.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Lanirapid

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 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 medicine in the SIGRE collection point at your pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Container Content and Additional Information

Lanirapid Composition

• The active ingredient is β-Methyldigoxin. Each tablet contains 0.1 mg of β-Methyldigoxin.
• The other components are lactose, microcrystalline cellulose (E-460(i)), potato starch carboxymethylamide, anhydrous colloidal silica, magnesium stearate, and povidone.

Product Appearance and Container Content

White, round, and scored tablet. The tablet can be divided into equal doses.

It is presented in standard containers of 50 tablets, packaged in PVC/Aluminum blisters.

Marketing Authorization Holder and Manufacturer

Kern Pharma, S.L.

Pol. Ind. Colón II, C/ Venus 72

08228 Terrassa (Barcelona)

Spain

Date of Last Revision of this Prospectus: November 2013.

Detailed and updated information about 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:

MODE OF USE:

Posology and Administration

Both the initial dose and the maintenance dose must be established individually for each patient, monitoring the plasma concentration.

The tablets of this medication should be taken without chewing, preferably after meals and with a little liquid.

The dose depends on the needs of cardiac glycosides and the elimination rate. The necessary amount will vary in case of patients with renal insufficiency, elderly people, and patients with thyroid function disorders (see section "Special Populations").

As a maintenance dose, most patients need 2 to 3 tablets a day (i.e., between 0.2 and 0.3 mg of β-methyldigoxin per day). In isolated cases, one tablet a day (0.1 mg of β-methyldigoxin per day) is sufficient. Only in patients with high glycoside needs is a daily maintenance dose of 0.4 mg of β-methyldigoxin (4 tablets per day) indicated.

The following table can serve as a guide for semi-rapid initiation treatment and for maintenance therapy with doses of 0.2 and 0.3 mg of β-methyldigoxin per day.

In severe cases of heart failure, and according to the individual's glycoside needs, a faster initiation treatment may be performed. For example, and in an orientative way, if it is determined that a person needs 0.6 mg of β-methyldigoxin per day (2 Lanirapid tablets 3 times a day) for 2 to 4 days, the effect level thus achieved would correspond to a daily maintenance dose of 0.2-0.4 mg of β-methyldigoxin.

Pediatric Population

There is no specific recommendation for the use of this medication in the pediatric population.

Special Populations

Patients with Renal Insufficiency:

In patients with renal insufficiency, the dose of methyldigoxin should be adjusted according to creatinine clearance. As a guide:

Creatinine clearance can be calculated using the Cockroft and Gault equation (only applicable to adults):

(140 – age [years] x weight [kg])

Men: Clcr [ml/min] = ———————————————

72 x Ccr [mg/dl]

CLcr = Creatinine clearance

Ccr = Serum creatinine concentration

Women: For women, creatinine clearance corresponds to 85% of the value obtained with this equation.

Elderly Patients:

In elderly patients, the dose of methyldigoxin should be adapted according to renal function. The decrease in renal function in this group of patients should be determined by calculating creatinine clearance.

Patients with Thyroid Function Disorders:

The dose of methyldigoxin should be adjusted according to the serum concentration of thyroid hormones. In patients with hypothyroidism, it may be necessary to reduce the dose of methyldigoxin. On the other hand, patients with hyperthyroidism may need higher doses of methyldigoxin.

OVERDOSE SYMPTOMS AND TREATMENT:

The therapeutic margin of digitalis glycosides is narrow.

Depending on cardiac sensitivity and glycoside needs, the therapeutic serum concentration of glycosides with this medication is approximately 1 ng/ml, while signs of glycoside intoxication can appear with values above 2 ng/ml.

Intoxication Symptoms

The clinical symptoms correspond to those of digitalis intoxication; there is no typical sequence in which they appear.

Cardiac symptoms (worsening of heart failure, ventricular or supraventricular arrhythmias, and conduction defects) and extracardiac symptoms (anorexia, hypersalivation, nausea, vomiting, diarrhea, abdominal pain, facial pain, headache, muscle weakness, dizziness, somnolence, disorientation, nightmares, apathy, depression, visual disturbances, and in very rare cases delirium, acute psychosis, and hallucinations) can appear simultaneously or consecutively. The cardiac signs of glycoside intoxication are much more severe than the extracardiac ones.

Digitoxin intoxications with a fatal outcome are a consequence of the cardiotoxic action of glycosides. Rhythm disturbances are especially important, such as polymorphic ventricular extrasystoles, ventricular flutter, ventricular fibrillation, and asystole. Beyond the glycoside dose, the severity of the intoxication symptoms depends on the potassium content of the extravascular and intracellular compartment.

Intoxication Treatment

If it has not been more than 4 hours since the ingestion of the tablets, immediate gastric lavage should be performed. The prior injection of atropine (0.5-1.0 mg subcutaneously) is highly recommended, especially in cases of bradycardic alterations. In all other cases, activated charcoal should be administered.

All treatment should be performed with ECG monitoring.

• Causal treatment, antidotes

A fragment of digoxin antibody has been developed for cases with a risk of death due to digitalis intoxication in which severe cardiac rhythm disturbances occur, or when disturbances that pose a risk of death due to accidental ingestion or after a suicide attempt are foreseen. The digitalis antidote is linked to digoxin, digoxin derivatives, and digitoxin in inactive antibody-glycoside complexes, rapidly inducing the causal elimination of the intoxication symptoms.

Forced diuresis, hemodialysis, and peritoneal dialysis have a slight influence on glycoside excretion. These techniques are, therefore, inappropriate for the treatment of digitalis intoxication.

• Symptomatic treatment

Mild toxicity manifestations are treated by temporarily suspending the medication, and if necessary, adding an oral potassium supplement (4 to 6 g/day in several doses, for adults with normal renal function).

Severe cases may require the administration of potassium intravenously (infusion of 20 mEq/hour up to a total of 40-100 mEq), for adults. In children, 0.5 mEq/kg/hour up to a maximum of 2 mEq/kg), under electrocardiogram control, and should be avoided in cases of advanced atrioventricular block or total block, due to digitalis and not related to tachycardia. Potassium administration is contraindicated in evident conduction disorders.

For convenience, a distinction is established in symptomatic treatment between tachycardic and bradycardic rhythm disturbances. However, a change to causal treatment with antibody fragments should always be considered at the right time:

• In bradycardic rhythm disturbances (heart rate below 60 ppm): it is recommended to administer atropine intravenously, 0.5 mg in adults and 0.02 mg/kg in children, repeatable every 5 minutes and up to a maximum of 4 times. If good results are not obtained with this, it may be necessary to install a pacemaker (provisional).

• For the treatment of tachycardias:
• • Supraventricular with signs of low output: Phenytoin (100 mg intravenously, repeatable at 5 minutes) can be used. In very specific cases where the patient does not respond to phenytoin, esmolol (0.5 mg/kg/intravenously in 1 minute, followed by continuous infusion of 0.05 mg/kg/min) can be tried. If there is no response to the previous drugs and these rhythm disturbances have hemodynamic repercussions, it will be necessary to resort to antibodies.
  • Ventricular arrhythmias: It is advised to use phenytoin or lidocaine. Phenytoin intravenously in a bolus of 50 mg per minute or through 100 mg every 5 minutes, until the arrhythmia is controlled or up to a maximum of 1 g in the adult or 20 mg/kg in the child. Lidocaine would be used in a bolus of 1.5 mg/kg intravenously followed by a continuous infusion of 2.5-4 mg/min in the adult and 50 micrograms/kg/min in the child.

• In the case of ventricular tachycardias without pulse, the initial treatment of choice is defibrillation.

Other agents used in the treatment of digitalis intoxication include calcium ion chelators, quinidine, procainamide, or beta-blockers. The latter three should also be used with caution in advanced cases of atrioventricular block.

The possibility of using cardioversion should be considered in case the causal treatment cannot be administered at the right time and if this symptomatic treatment does not yield good results.