1. Name of the medicinal product

Amiodarone Hydrochloride for Injection USP 150mg/3ml Taj Pharma
Amiodarone Hydrochloride for Injection USP 450mg/9ml Taj Pharma
Amiodarone Hydrochloride for Injection USP 900mg/18ml Taj Pharma

  1. Qualitative and quantitative composition

a) Amiodarone Hydrochloride for Injection USP 150mg/3ml Taj Pharma
Each 3ml ampoule contains:
Amiodarone Hydrochloride USP 150mg
Excipients: Q.S.

b) Amiodarone Hydrochloride for Injection USP 450mg/9ml Taj Pharma
Each 9ml ampoule contains:
Amiodarone Hydrochloride USP 450mg
Excipients: Q.S.

c) Amiodarone Hydrochloride for Injection USP 900mg/18ml Taj Pharma
Each 18ml ampoule contains:
Amiodarone Hydrochloride USP 900mg
Excipients: Q.S.

Excipient with known effect: benzyl alcohol

For the full list of excipients, see section 6.1.

  1. Pharmaceutical form

Concentrate for Solution for Injection/Infusion.

  1. Clinical particulars
    • Therapeutic indications

Treatment should be initiated and normally monitored only under hospital or specialist supervision.

Amiodarone Taj Pharma is indicated only for the treatment of severe rhythm disorders not responding to other therapies or when other treatments cannot be used:

  • tachyarrhythmias associated with Wolff-Parkinson-White syndrome
  • life-threatening ventricular arrhythmias, including persistent or non-persistent ventricular tachycardia or episodes of ventricular fibrillation, cardiopulmonary resuscitation in case of cardiac arrest related to ventricular fibrillation resistant to defibrillation; when other active substances cannot be used
  • all other types of tachyarrhythmias including supraventricular, nodal and ventricular tachycardias; atrial flutter and fibrillation.

Amiodarone Taj Pharma can be used where a rapid response is required or where oral administration is not possible.

  • Posology and method of administration

Amiodarone Taj Pharma should only be used when facilities exist for cardiac monitoring, defibrillation, and cardiac pacing. See section 6.6. Amiodarone Taj Pharma may be used prior to direct current (DC) cardioversion.

Posology

Adults

Infusion

Loading dose:

The standard recommended dose is 5mg/kg bodyweight given by intravenous infusion over a period of 20 minutes to 2 hours. This should be administered as a dilute solution in 250ml 5% dextrose. This may be followed by repeat infusion up to 1200mg (approximately 15mg/kg bodyweight) in up to 500ml 5% dextrose per 24 hours, the rate of infusion being adjusted on the basis of clinical response (see section 4.4).

The therapeutic effect is visible in the first minutes, then decreased gradually, and should be followed by a maintenance infusion.

Maintenance dose:

10 – 20mg per kg bw in physiological glucose solution every 24 hours (on average 600 to 800mg/ 24 hours up to a maximum of 1200mg/ 24 hours accordingly 4-5 ampoules, maximum 8 ampoules) for a few days. On account of the stability of the solution, do not use concentrations below 300mg per 500ml and do not add other medicinal products to the infusion fluid.

To prevent local reactions (phlebitis), do not use concentrations exceeding 3mg/ml.

Repeated or continuous infusions via peripheral veins may lead to local reactions (inflammation).

Whenever repeated or continuous infusions are intended, administration via a central line is recommended.

Injection

In extreme clinical emergency, Amiodarone Taj Pharma may at the discretion of the clinician, be given as a slow injection of 150-300mg (or 2.5 – 5mg/kg) in 10-20ml 5% glucose over a minimum of 3 minutes. This should not be repeated for at least 15 minutes. Patients treated in this way with Amiodarone Taj Pharma must be closely monitored, e.g. in an intensive care unit (see section 4.4).

Method of administration

Amiodarone Taj Pharma should be administered by a central venous route, except for cardiopulmonary resuscitation in case of cardiac arrest related to ventricular fibrillation resistant to defibrillation, where peripheral venous route could be used (see section 4.4).

Changeover from intravenous to oral use

As soon as an adequate response has been obtained (if possible, commence oral maintenance dose on the first day of the infusion), oral therapy should be initiated concomitantly at the usual loading dose (i.e. 200mg three times a day). Amiodarone Taj Pharma should then be phased out gradually.

In patients taking Amiodarone Taj Pharma concomitantly with simvastatin, the dose of simvastatin should not exceed 20mg/day (see sections 4.4, 4.5).

Paediatric population

The safety and efficacy of Amiodarone Taj Pharma in children has not been established.

Currently available data are described in sections 5.1 and 5.2.

Due to the presence of benzyl alcohol, Amiodarone Taj Pharma intravenous administration is contraindicated in neonates, infants and children up to 3 years old.

Elderly

As with all patients it is important that the minimum effective dose is used. Whilst there is no evidence that dosage requirements are different for this group of patients they may be more susceptible to bradycardia and conduction defects if too high a dose is employed. Particular attention should be paid to monitoring thyroid function (see sections 4.3, 4.4 and 4.8).

Cardiopulmonary resuscitation

Administration by a central venous catheter is recommended when it is immediately available. If not, the administration must be done by a peripheral venous route, using a large peripheral vein and with a flow as important as possible, or possibly, by a slow injection over a minimum of 3 minutes, followed by administration of 200ml of infusion fluid. Do not give other medicinal substances in the same syringe with Amiodarone Taj Pharma. Amiodarone Taj Pharma can cause severe irritation of the vein, therefore adequate rinsing after bolus injection must be ensured. In treatment of prolonged, refractory ventricular fibrillation, after administration of adrenaline and defibrillation, 300mg as bolus injection and repeated, if necessary, with 150mg bolus injection.

The recommended dose for ventricular fibrillations/pulseless ventricular tachycardia resistant to defibrillation is 300mg (or 5mg/kg body-weight) diluted in 20ml 5% dextrose and rapidly injected. An additional 150mg (or 2.5mg/kg body-weight) IV dose may be considered if ventricular fibrillation persists.

Patients with liver and kidney problems

Although no dosage adjustment for patients with kidney or liver abnormalities has been defined during chronic treatment with oral Amiodarone Taj Pharma, close clinical monitoring is prudent for elderly patients.

For instructions on dilution of the sterile concentrate before administration, see section 6.6.

See section 6.2 for information on incompatibilities

  • Contraindications
  • Hypersensitivity to iodine or to Amiodarone Taj Pharma, or to any of the excipients listed in section 6.1 (one ampoule contains approximately 56mg iodine).
  • Sinus bradycardia, sino-atrial heart block. In patients with severe conduction disturbances (high grade AV block, bifascicular or trifascicular block) or sinus node disease, Amiodarone Taj Pharma should be used only in conjunction with a pacemaker.
  • Combination of Amiodarone Taj Pharma with drugs which may induce torsades de pointes (see section 4.5).
  • Severe respiratory failure, circulatory collapse, or severe arterial hypotension; hypotension, heart failure and cardiomyopathy are also contraindications when using Amiodarone Taj Pharma as a bolus injection. However, these contraindications are not absolute and the use is allowed only under strict supervision with the greatest caution possible.
  • Evidence or history of thyroid dysfunction. Thyroid function tests should be performed where appropriate prior to therapy in all patients.
  • Due to the presence of benzyl alcohol, Amiodarone Taj Pharma is contraindicated in neonates, infants and children up to 3 years old.
  • Pregnancy and lactation. The use is allowed only in special life-threatening circumstances as specified in the second indication (see sections 4.1, 4.4 and 4.6).

Not all these above contra-indications apply to the use of Amiodarone Taj Pharma for cardiopulmonary resuscitation of shock resistant ventricular fibrillation.

  • Special warnings and precautions for use

Data of the SEARCH Study verify an increased risk of myopathy/rhabdomyolysis in combined use of Amiodarone Taj Pharma and simvastatin, which varies with the daily dose of simvastatin. The pharmacological mechanism on which this interaction is based is not known.

The indication for concomitant therapy of Amiodarone Taj Pharma with a statin should therefore be made with special caution. As no risk of myopathy/rhabdomyolysis is assumed only in case of a combined daily dose of Amiodarone Taj Pharma with simvastatin at low daily dose ≤ 20mg, this simvastatin dose should not be exceeded. Other statins than simvastatin should be used at low dosage in concomitant therapy with Amiodarone Taj Pharma (see sections 4.2, 4.5).

Amiodarone Taj Pharma may only be prescribed by competent specialists. Only to be used when other antiarrhythmics have shown insufficient effect. The patients must be monitored closely during treatment for radiological lungs examination, thyroid gland function and liver function test and ECG.

Amiodarone Taj Pharma should only be used in a special care unit under continuous monitoring (ECG and blood pressure).

Administration of direct i.v. injections (bolus injections) is discouraged due to the risk of haemodynamic effects, such as serious hypotension and cardiovascular collapse. Such injections should only be used in an emergency – within a coronary intensive care unit and under ECG monitoring – when therapeutic alternatives have failed. Circulatory collapse may be precipitated by too rapid administration or overdosage (atropine has been used successfully in such patients presenting with bradycardia).

Its use should proceed with extreme caution – with haemodynamic monitoring – in patients with severe pulmonary impairment, arterial hypotension or stable congestive heart failure. Such patients should not be given a bolus injection (risk of exacerbation).

The proposed dose of 5mg per kg, given as a direct injection, must not be exceeded.

If the effect of this product is too strong (e.g. severe bradycardia), appropriate measures should be taken, i.e. use of a pacemaker or beta stimulation.

The undiluted solution has not been adequately assessed for safety therefore, it is recommended not to use the solution for injection without prior dilution.

Repeated or continuous infusion via peripheral veins may lead to injection site reactions (see section 4.8). When repeated or continuous infusion is anticipated, administration by a central venous catheter is recommended.

When given by infusion Amiodarone Taj Pharma may reduce drop size and, if appropriate, adjustments should be made to the rate of infusion.

Anaesthesia (see section 4.5): Before surgery, the anaesthetist should be informed that the patient is taking Amiodarone Taj Pharma.

Cardiac disorders:

Caution should be exercised in patients with hypotension and decompensated cardiomyopathy and severe heart failure (also see section 4.3).

Amiodarone Taj Pharma has a low pro-arrhythmic effect. Onsets of new arrhythmias or worsening of treated arrhythmias, sometimes fatal, have been reported. It is important, but difficult to differentiate a lack of efficacy of the drug from a proarrhythmic effect, whether or not this is associated with a worsening of the cardiac condition. Proarrhythmic effects with Amiodarone Taj Pharma are rarely referred comparing with other anti-rhythmic agents and generally occur in the context of drug interactions and/or electrolytic disorders (see sections 4.5 and 4.8).

Too high a dosage may lead to severe bradycardia and to conduction disturbances with the appearance of an idioventricular rhythm, particularly in elderly patients or during digitalis therapy. In these circumstances, Amiodarone Taj Pharma treatment should be withdrawn. If necessary, beta-adrenostimulants or glucagon may be given. Because of the long half-life of Amiodarone Taj Pharma, if bradycardia is severe and symptomatic the insertion of a pacemaker should be considered. The pharmacological action of Amiodarone Taj Pharma induces ECG changes: QT prolongation (related to prolonged repolarisation) with the possible development of U-waves and deformed T-waves; these changes do not reflect toxicity. As with some other anti-arrhythmic agents, this phenomenon can lead to atypical ventricular tachycardias (“torsade de pointes”) in exceptional cases.

Respiratory, thoracic and mediastinal disorders (see section 4.8):

Very rare cases of interstitial pneumonitis have been reported with intravenous Amiodarone Taj Pharma. When the diagnosis is suspected, a chest X-ray should be performed. Amiodarone Taj Pharma therapy should be re-evaluated since interstitial pneumonitis is generally reversible and resolve rapidly following early withdrawal of Amiodarone Taj Pharma, and corticosteroid therapy should be considered (see section 4.8). Clinical symptoms often resolve within a few weeks followed by slower radiological and lung function improvement. Some patients can deteriorate despite discontinuing Amiodarone Taj Pharma. Fatal cases of pulmonary toxicity have been reported.

Very rare cases of severe respiratory complications, sometimes fatal, have been observed usually in the period immediately following surgery (adult acute respiratory distress syndrome); a possible interaction with a high oxygen concentration may be implicated (see sections 4.5 and 4.8).

Hepato-biliary disorders (see section 4.8)

It is recommended to monitor hepatic function (transaminases) after initiation and during treatment with Amiodarone Taj Pharma.

Acute hepatic dysfunctions (including severe hepatocellular insufficiency or hepatic impairment, sometimes fatal) may occur, and also chronic hepatic dysfunctions, with the intravenous administration forms, within the first 24 hours of IV Amiodarone Taj Pharma, and may sometimes be fatal. Close monitoring of transaminases is therefore recommended as soon as Amiodarone Taj Pharma is started.

There may be clinical and biological signs of liver abnormalities due to chronic oral administration of Amiodarone Taj Pharma, which may be minimal (hepatomegaly, elevated transaminases 5 times above normal values) and reversible after discontinuation of treatment. However fatal cases were reported. Consequently, the Amiodarone Taj Pharma dose should be reduced or treatment discontinued if the transaminases increase exceeds three times the normal values.

Eye disorders (see section 4.8)

During treatment with Amiodarone Taj Pharma hydrochloride, regular ophthalmic examinations are indicated – including funduscopy and examinations by means of a slit-lamp.

Skin and subcutaneous tissue disorder (see section 4.8)

Exposure to sunlight should be avoided during therapy with Amiodarone Taj Pharma hydrochloride; this also applies to UV light applications and solaria. If this is not possible, uncovered skin parts, particularly the face, are to be protected by application of an ointment with a high protection factor. Even after withdrawal of Amiodarone Taj Pharma hydrochloride, a light protector is necessary for some more time.

Endocrine disorders (see section 4.8)

Due to the risk of developing a thyroid dysfunction (hyperthyroidism or hypothyroidism) during treatment with Amiodarone Taj Pharma hydrochloride, thyroid function should be examined prior to the onset of treatment. During therapy and up to one year after its withdrawal, these examinations should be repeated at regular intervals and the patients examined for clinical symptoms of hyperthyroidism or hypothyroidism.

Amiodarone Taj Pharma hydrochloride inhibits the conversion of thyroxine (T4) into triiodothyronine (T3) and may lead to increased T4 values as well as to decreased T3 values in (euthyroid) patients without clinical symptoms. This findings constellation alone should not result in discontinuing therapy.

The clinical diagnosis of hypothyroidism is confirmed by proof of considerably increased ultrasensitive TSH value as well as decreased T4 value. By proof of hypothyroidism, the Amiodarone Taj Pharma hydrochloride dosage should be reduced – if possible – and/or substitution with L-thyroxine started. In isolated cases, discontinuation of Amiodarone Taj Pharma hydrochloride may be required.

The clinical diagnosis of hyperthyroidism is confirmed by proof of considerably decreased ultrasensitive TSH as well as increased T3 and T4 values. By proof of hyperthyroidism, the dosage should be reduced – if possible – or Amiodarone Taj Pharma hydrochloride discontinued; in severe cases, treatment with thyroid depressants, beta-adrenergic blocking agents and/or corticosteroids should be initiated.

On account of its iodine content, Amiodarone Taj Pharma hydrochloride falsifies classic thyroid tests (iodine binding test).

Nervous system disorders (see section 4.8):

Amiodarone Taj Pharma may induce peripheral sensorimotor neuropathy and/or myopathy. Both these conditions may be severe, although recovery usually occurs within several months after Amiodarone Taj Pharma withdrawal, but may sometimes be incomplete.

Interactions with other medicinal products (see section 4.5)

Concomitant use of Amiodarone Taj Pharma with the following drugs is not recommended: beta-blockers, heart rate lowering calcium channel inhibitors (verapamil, diltiazem), stimulant laxative agents which may cause hypokalaemia.

Increased plasma levels of flecainide have been reported with co-administration of Amiodarone Taj Pharma. The flecainide dose should be reduced accordingly and the patient closely monitored.

After ending of the therapy there might be a still effective concentration of Amiodarone Taj Pharma in the blood serum for some weeks in case of a repeated intravenous administration because of the long half-life of Amiodarone Taj Pharma. After further subsidence of the Amiodarone Taj Pharma-level, arrhythmias can recur. Patients should be monitored regularly after ending of the therapy.

Paediatric population

Safety and efficacy of Amiodarone Taj Pharma hydrochloride in paediatric patients have not been established. Therefore its use in paediatric patients is not recommended, but if essential, the use is to be under the supervision of a paediatric cardiologist. No controlled paediatric studies have been undertaken. In published uncontrolled studies effective doses for children were identified see (see section 4.2).

Amiodarone Taj Pharma injection contains benzyl alcohol (20mg/ml).

Benzyl alcohol may cause toxic reactions and allergic reactions in infants and children up to 3 years old.

  • Interaction with other medicinal products and other forms of interaction

In view of the long and variable half-life of Amiodarone Taj Pharma (approximately 50 days), potential for interactions with other medicinal products exists not only with concomitant medication but also with medicinal products administered after discontinuation of Amiodarone Taj Pharma.

Some of the more important active substances that interact with Amiodarone Taj Pharma include oral anticoagulants (warfarin), digoxin, phenytoin and any active substances which prolongs the QT interval.

Amiodarone Taj Pharma raises the plasma concentrations of oral anticoagulants (warfarin) by inhibition of CYP 2C9. The dose of anticoagulants (warfarin) should be reduced accordingly. More frequent monitoring of prothrombin time both during and after Amiodarone Taj Pharma treatment is recommended.

Similar to anticoagulants, by inhibition of CYP 2C9, Amiodarone Taj Pharma also interacts with phenytoin. Phenytoin dosage should be reduced if signs of overdosage appear, and plasma levels may be measured.

Administration of Amiodarone Taj Pharma to a patient already receiving digoxin will bring about an increase in the plasma digoxin concentration and thus precipitate symptoms and signs associated with high digoxin levels. Clinical, ECG and biological monitoring is recommended and digoxin dosage should be halved. A synergistic effect on heart rate and atrioventricular conduction is also possible.

Combined therapy with the following drugs which prolong the QT interval is contra-indicated (see section 4.3) due to the increased risk of torsades de pointes; for example:

  • Class Ia anti-arrhythmic drugs e.g. quinidine, procainamide, disopyramide
  • Class III anti-arrhythmic drugs e.g. sotalol, bretylium, dofetilide and ibutilide
  • intravenous erythromycin, co-trimoxazole (trimethoprim-sulfamethoxazole) or pentamidine injection
  • some anti-psychotics e.g. chlorpromazine, thioridazine, fluphenazine, pimozide, haloperidol, amisulpride and sertindole
  • lithium and tricyclic anti-depressants e.g. doxepin, maprotiline, amitriptyline
  • certain antihistamines e.g. terfenadine, astemizole, mizolastine
  • anti-malarials e.g. quinine, mefloquine, chloroquine, halofantrine, lumefantrine
  • gastrointestinal agents e.g. cisapride, droperidol.
  • Combined therapy with the following active substances is not recommended:
  • bradycardic active substances such as beta blockers, anticholinesterases (e.g. neostigmine) and certain calcium channel inhibitors (diltiazem, verapamil); potentiation of negative chronotropic properties and conduction slowing effects may occur.
  • Hypokalaemic active substances such as stimulant laxatives, diuretics, systemic corticosteroids, tetracosactide, intravenous amphotericin which may cause hypokalaemia and/or hypomagnesaemia thus increasing the risk of torsades de pointes; other types of laxatives should be used.

In cases of hypokalaemia, corrective action should be taken and QT interval monitored. In case of torsades de pointes antiarrhythmic agents should not be given; pacing may be instituted and IV magnesium may be used.

Caution is advised in patients undergoing general anaesthesia, or receiving high dose oxygen therapy. Potentially severe complications have been reported in patients taking Amiodarone Taj Pharma undergoing general anaesthesia: bradycardia unresponsive to atropine, hypotension, disturbances of conduction, decreased cardiac output. A few cases of adult respiratory distress syndrome, most often in the period immediately after surgery, have been observed. A possible interaction with a high oxygen concentration may be implicated.

Grapefruit juice also inhibits cytochrome P450 3A4 and may increase the plasma concentration of Amiodarone Taj Pharma. Grapefruit juice should be avoided during treatment with Amiodarone Taj Pharma.

Active substances metabolised by cytochrome P450 3A4

When such medicinal products are co-administered with Amiodarone Taj Pharma, an inhibitor of CYP 3A4, this may result in a higher level of their plasma concentrations, which may lead to a possible increase in their toxicity:

  • Ciclosporin: plasma levels of ciclosporin may increase as much as 2-fold when used in combination. A reduction in the dose of ciclosporin may be necessary to maintain the plasma concentration within the therapeutic range.
  • Other active substances metabolised by cytochrome P450 3A4 are: the statins, lidocaine, tacrolimus, sildenafil, fentanyl, midazolam and ergotamine.
  • Simvastatin (at doses higher than 20mg/day) in combination with amiodaron has been associated with an increased risk of myopathy/rhabdomyolysis (see sections 4.2, 4.4).

Flecainide

Given that flecainide is mainly metabolised by CYP 2D6, by inhibiting this isoenzyme, Amiodarone Taj Pharma may increase flecainide plasma levels; it is advised to reduce the flecainide dose by 50% and to monitor the patient closely for adverse effects. Monitoring of flecainide plasma levels is strongly recommended in such circumstances.

Interaction with substrates of other CYP 450 isoenzymes

In vitro studies show that Amiodarone Taj Pharma also has the potential to inhibit CYP 1A2, CYP 2C19 and CYP 2D6 through its main metabolite. When co-administered, Amiodarone Taj Pharma would be expected to increase the plasma concentration of drugs whose metabolism is dependent upon CYP 1A2, CYP 2C19 and CYP 2D6.

  • Fertility, pregnancy and lactation

Pregnancy

Data on a limited number of exposed pregnancies are available. Amiodarone Taj Pharma and N-desmethylAmiodarone Taj Pharma cross the placental barrier and achieve 10-25% of the maternal plasma concentrations in the infant. Most frequent complications include impaired growth, preterm birth and impaired function of the thyroid gland in newborn babies. Hypothyroidism, bradycardia and prolonged QT intervals were observed in approximately 10 % of the newborn babies. In isolated cases an increased thyroid gland or cardiac murmurs were found. The malformation rate does not appear to be increased. However, the possibility of cardiac defects should be kept in mind. Therefore, Amiodarone Taj Pharma must not be used during pregnancy unless clearly necessary and the real risk of reoccurrence of life threatening arrhythmias should be weighed against the possible hazard for the fetus. Given the long half-life of Amiodarone Taj Pharma, women of child-bearing age would need to plan for a pregnancy starting at least half a year after finishing therapy, in order to avoid exposure of the embryo/fetus during early pregnancy.

Breastfeeding

The passage into mother’s milk is proven for the active ingredient and for the active metabolite. If therapy is required during the lactation period, or if Amiodarone Taj Pharma was taken during pregnancy, breast-feeding should be stopped.

Fertility

Elevated serum levels of LH and FSH were found in male patients after long-term treatment indicating testicular dysfunctions.

  • Effects on ability to drive and use machines

There are no known data available. As blurred and/or reduced vision may occur, a possible effect on the ability to drive and use machines should be considered.

  • Undesirable effects

The following adverse reactions are classified by system organ class and ranked under heading of MedDRA frequency convention: very common ≥1/10), common≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000), very rare (<1/10000); Not known (cannot be estimated from available data).

Endocrine disorders (see section 4.4):

Common:

  • hypothyroidism
  • hyperthyroidism, sometimes fatal

Very rare:

  • syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Eye disorders (see section 4.4):

Very common:

  • micro-deposits at the anterior surface of the cornea are found in almost every patient, which are usually limited to the area below the pupil. They may be associated with colored halos in dazzling light or blurred vision. They usually regress 6-12 months after discontinuation of Amiodarone Taj Pharma hydrochloride

Very rare:

  • optic neuropathy/neuritis that may progress to blindness

Cardiac disorders:

Common:

  • bradycardia, generally moderate

Very rare:

  • marked bradycardia, sinus arrest requiring discontinuation of Amiodarone Taj Pharma, especially in patients with sinus node dysfunction and/or in elderly patients
  • onset of worsening of arrhythmia, sometimes followed by cardiac arrest (see sections 4.4 and 4.5)

Gastrointestinal disorders:

Very rare:

  • nausea

Unknown:

  • pancreatitis (acute)

General disorders and administration site conditions:

Common:

  • injection site reactions such as pain, erythema, oedema, necrosis, extravasation, infiltration, inflammation, induration, thrombophlebitis, phlebitis, cellulitis, infection, pigmentation changes

Hepato-biliary disorders:

Very rare:

  • isolated increase in serum transaminases, which is usually moderate (1.5 to 3 times normal range) at the beginning of therapy. They may return to normal with dose reduction or even spontaneously
  • acute liver disorders with high serum transaminases and/or jaundice, including hepatic failure, sometimes fatal (see section 4.4)

Immune system disorders:

Rare:

  • the excipients benzyl alcohol may cause hypersensitivity reactions

Very rare:

  • anaphylactic shock

Nervous system disorders:

Common:

  • extrapyramidal tremor, for which regression usually occurs after reduction of dose or withdrawal

Uncommon:

  • peripheral sensorimotor neuropathy and/or myopathy, usually reversible on withdrawal of the drug (see section 4.4)
  • dizziness

Very rare:

  • cerebellar ataxia, for which regression usually occurs after reduction of dose or withdrawal
  • benign intracranial hypertension (pseudo-tumor cerebri)
  • headache
  • vertigo

Psychiatric disorders:

Common:

  • nightmares
  • sleep disorders
  • Not known:
  • hallucinations
  • delirium (including confusion)

Musculoskeletal and connective tissue disorders:

Common:

  • muscle weakness

Respiratory, thoracic and mediastinal disorders:

Very rare:

  • interstitial pneumonitis (see section 4.4)
  • severe respiratory complications (adult acute respiratory distress syndrome), sometimes fatal (see sections 4.4 and 4.5)
  • bronchospasm and/or apnoea in case of severe respiratory failure, and especially in asthmatic patients.

Skin and subcutaneous tissue disorders:

Very common:

  • photosensitivity (see section 4.4).

Common:

  • eczema
  • slate grey or bluish pigmentations of light-exposed skin, particularly the face, in case of prolonged treatment with high daily dosages; such pigmentations slowly disappear following treatment discontinuation.

Very rare:

  • sweating
  • erythema during the course of radiotherapy
  • skin rashes, usually non-specific
  • exfoliative dermatitis.

Unknown:

  • severe skin reaction as toxic epidermal necrolysis (TEN)/Stevens- Johnson syndrome (SJS), bullous dermatitis and Drug reaction with eosinophilia and systematic symptoms (DRESS).

Vascular disorders:

Common:

  • decrease in blood pressure, usually moderate and transient. Cases of hypotension or collapse have been reported following overdosage or a too rapid injection.

Very rare:

  • hot flushes

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

Overdose

There is no information regarding overdosage with intravenous Amiodarone Taj Pharma.

Little information is available regarding acute overdosage with oral Amiodarone Taj Pharma. Few cases of sinus bradycardia, heart block, attacks of ventricular tachycardia, torsades de pointes, circulatory failure and hepatic injury have been reported.

In the event of overdose, treatment should be symptomatic, in addition to general supportive measures.

The patient should be monitored and if bradycardia occurs beta-adrenostimulants or glucagon may be given.

Spontaneously resolving attacks of ventricular tachycardia may also occur. Due to the pharmacokinetics of Amiodarone Taj Pharma, adequate and prolonged surveillance of the patient, particularly cardiac status, is recommended.

Neither Amiodarone Taj Pharma nor its metabolites are dialyzable.

  1. Pharmacological properties
  • Pharmacodynamic properties

Pharmacotherapeutic group: 3.2.3. Cardiovascular apparatus. Antiarrhythmic, Repolarization lengtheners (Class III);

Amiodarone Taj Pharma is a di-iodinated benzofuran derivative and is classified as a class III antiarrhythmic agent owing to its ability to increase the cardiac action potential duration in both atrial and ventricular myocytes via block of cardiac K+ channels (mainly of the rapid component of the delayed rectifier K+ current, IKr). Thus, it prolongs the refractory period of the action potential leading to depression of ectopies and re-entry-arrhythmias and to prolongation of the QTc interval in the ECG. Furthermore, Amiodarone Taj Pharma also blocks cardiac Na+ currents (class I effect) and Ca2+ currents (class IV effect). The latter may lead to slowing of conduction through the sinoatrial and atrioventricular nodes. During long-term administration, Amiodarone Taj Pharma also seems to inhibit the trafficking of ion channels from the endoplasmic reticulum to the plasma membrane in cardiac myocytes, and these effects may contribute to the cardiac electrophysiological actions of Amiodarone Taj Pharma under chronic administration. Furthermore, Amiodarone Taj Pharma is a non-competitive antagonist at both ß- and α-adrenoceptors and, therefore, has haemodynamic effects: dilatation of coronary arteries and peripheral vasodilation leading to a reduction of systemic blood pressure. Negative inotropic, negative chronotropic and negative dromotropic effects seem to be induced by the ß-adrenergic antagonistic effects induced by Amiodarone Taj Pharma. Some effects of Amiodarone Taj Pharma are comparable with hypothyroidism, which might be due to inhibition of thyroid hormone synthesis. Amiodarone Taj Pharma is a potent inhibitor of iodothyronine-5´-monodeiodinase activity (the main T4-T3 converting enzyme). In rats, increases in serum thyroid-stimulating hormone (TSH), thyroxine (T4) and reverse triiodothyronine (rT3), and decreases in serum triiodothyronine (T3) as a result of inhibition of deiodination of T4 to T3 have been observed. These antithyroid actions of Amiodarone Taj Pharma might contribute to its cardiac electrophysiological effects.

The main metabolite N-desethylAmiodarone Taj Pharma has effects on cardiac electrophysiology similar to those of the parent compound

Cardiopulmonary resuscitation in case of cardiac arrest related to ventricular fibrillation resistant to defibrillation

The safety and efficacy of IV Amiodarone Taj Pharma in patients with cardiac arrest, in hospital, due to ventricular fibrillation resistant to defibrillation were evaluated in two double blinded clinical trials: the ARREST study, that compares Amiodarone Taj Pharma with placebo, and the ALIVE study, that compares Amiodarone Taj Pharma with lidocaine. The primary endpoint of both trials was the survival after hospital admission.

In the ARREST study, there were randomized 504 patients with cardiac arrest in hospital due to ventricular fibrillations/pulseless ventricular tachycardia resistant to three or more defibrillation and adrenaline, of which 246 patients received 300mg of Amiodarone Taj Pharma diluted in 20ml 5% dextrose by bolus injection in peripheral vein, and 258 patients with placebo. From the 197 patients that survived (39%), Amiodarone Taj Pharma increased significantly the resuscitation scenario and inpatient hospital: 44% in the group of Amiodarone Taj Pharma and 34% in the group of placebo, respectively (p=0.03). After amendment of other outcome predictors, the adjusted ratio of the likelihood of survival at hospital admission in the group of Amiodarone Taj Pharma compared to the placebo group was 1.6 (95% confidence interval, 1.1 to 2.4; p=0.02). There were more patients with hypotension in the group treated with Amiodarone Taj Pharma than in placebo’s group (59% vs 25%, p=0.04) or with bradycardia (41% vs 25%, p=0.004).

In the ALIVE study, there were randomized 347 patients with ventricular fibrillation resistant to three electric defibrillations, adrenaline and another electric defibrillation, or with recurrent ventricular fibrillation after successful initial defibrillation, some with Amiodarone Taj Pharma (5mg/kg at a 10mg/ml concentration) and placebo corresponding to lidocaine, or with lidocaine (1.5mg/kg at a 10mg/ml concentration) and placebo corresponding to Amiodarone Taj Pharma with the same diluent (polysorbate 80). From the 347 patients included, it was established that Amiodarone Taj Pharma increased the resuscitation scenario and inpatient hospital: 22.8% in the Amiodarone Taj Pharma’s group (41 patients from 180) and 12% in the lidocaine group (20 patients from 167), p=0.009. After adjustment to other factors that may affect the likelihood of survival, the adjusted ratio of the survival likelihood to hospital admission in the group of Amiodarone Taj Pharma, when compared with the group of lidocaine was 2.49 (95% confidence interval, 1.28 to 4.85; p=0.007). There were no differences between the two groups concerning the percentage of patients who needed medication for bradycardia, with atropine or vasoconstrictor treatment with dopamine, not either concerning the percentage of patients receiving open lidocaine. The percentage of patients that had asystole as a consequence of the defibrillation after the administration of the initial treatment was significantly higher in the group of lidocaine (28,9%) than in the group of Amiodarone Taj Pharma (18.4%), p=0.04.

The proportion of patients in whom asystole occurred following defibrillation shock after administration of the initial study drug was significantly higher in the lidocaine group (28.9%) than in the Amiodarone Taj Pharma group (18.4%) , p = 0.04.

Paediatric population

No controlled paediatric studies have been undertaken.

In published studies the safety of Amiodarone Taj Pharma was evaluated in 1118 paediatric patients with various arrhythmias. The following doses were used in paediatric clinical trials.

Oral

  • Loading dose: 10 to 20mg/kg/day for 7 to 10 days (or 500mg/m2/day if expressed per square meter)
  • Maintenance dose: the minimum effective dosage should be used; according to individual response, it may range between 5 to 10mg/kg/day (or 250mg/m2/day if expressed per square meter)

Intravenous

  • Loading dose: 5mg/kg body weight over 20 minutes to 2 hours,
  • Maintenance dose: 10 to 15mg/kg/day from few hours to several days

If needed oral therapy may be initiated concomitantly at the usual loading dose.

  • Pharmacokinetic properties

Pharmacokinetics of Amiodarone Taj Pharma are unusual and complex, and have not been completely elucidated.

Absorption

Absorption following oral administration is variable and may be prolonged, with enterohepatic cycling.

Distribution

Amiodarone Taj Pharma is highly protein bound > 95%).

A study in both healthy volunteers and patients after intravenous administration of Amiodarone Taj Pharma reported that the calculated volumes of distribution and total blood clearance using a two-compartment open model were similar for both groups.

The very high volume of distribution combined with a relatively low apparent volume for the central compartment suggests extensive tissue distribution. A bolus IV injection of 400mg gave a terminal T½ of approximately 11 hours.

Biotransformation

The major metabolite is desethylAmiodarone Taj Pharma.

Elimination

Renal excretion is minimal and faecal excretion is the major route.
Elimination of Amiodarone Taj Pharma after intravenous injection appeared to be biexponential with a distribution phase lasting about 4 hours.

Paediatric population

No controlled paediatric studies have been undertaken. In the limited published data available in paediatric patients, there were no differences noted compared to adults.

  • Preclinical safety data

In chronic toxicity studies, Amiodarone Taj Pharma led to pulmonary damage (fibrosis, phospholipidosis; in hamsters, rats and dogs). Pulmonary toxicity appears to result from radical formation and perturbation of cellular energy production. In addition, Amiodarone Taj Pharma caused liver damage in rats.

Regarding the genotoxicity aspects the in vitro Ames test and in vivo mouse bone marrow micronucleus test have been conducted. Both studies yielded negative results.

In a 2-year carcinogenicity study in rats, Amiodarone Taj Pharma caused an increased incidence of thyroid follicular tumours (adenomas and/or carcinomas) in both sexes at clinical relevant exposures. Since mutagenicity findings were negative, an epigenic rather than genotoxic mechanism is proposed for this type of tumour induction. In the mouse, carcinomas were not observed, but a dose-dependent thyroid follicular hyperplasia was seen. These effects on the thyroid in rats and mice are most likely due to effects of Amiodarone Taj Pharma on the synthesis and/or release of thyroid gland hormones. The relevance of these findings to man is low.

  1. Pharmaceutical particulars
  • List of excipients

Polysorbate 80, Benzyl alcohol, Hydrochloride acid or Sodium Hydroxide, Water for injection

  • Incompatibilities

The use of administration equipment or devices containing plasticizers such as DEHP (di-2-ethylhexylphthalate) in the presence of Amiodarone Taj Pharma may result in leaching out of DEHP. In order to minimise patient exposure to DEHP, the final Amiodarone Taj Pharma dilution for infusion should preferably be administered through non DEHP-containing sets.

See section 6.6, “Special precautions for disposal and other handling”

  • Shelf life

3 years

  • Special precautions for storage

Do not store above 25°C.
Do not refrigerate or freeze. Storage at low temperature may cause the formation of precipitate. Do not use unless solution is clear.
Store in the original container.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

  • Nature and contents of container

Each carton contains 5 or 10 glass ampoules.

  • Special precautions for disposal and other handling

Amiodarone Taj Pharma is incompatible with saline and should be administered solely in 5% dextrose solution. Amiodarone Taj Pharma diluted with 5% dextrose solution to a concentration of less than 0.6mg/ml is unstable. Solutions containing less than two ampoules Amiodarone Taj Pharma in 500ml dextrose 5% are unstable and should not be used.

For single dose use only. Discard any unused solution immediately after initial use.

The dilution is to be made under aseptic conditions. Before use, the sterile concentrate should be visually inspected for clarity, particulate matter, discolouration and the integrity of the container. The solution should only be used if it is clear, free from particles and the container is undamaged and intact.

Prior to administration by intravenous infusion, Amiodarone Taj Pharma should be diluted according to directions with the recommended infusion fluid, 5% w/v Glucose Intravenous Infusion. The contents of one ampoule of the sterile concentrate diluted as recommended in 250ml of 5% w/v Glucose Intravenous infusion contains 0.6mg/ml of Amiodarone Taj Pharma.

Solutions containing 150mg/3ml, 450mg/9ml and 900mg/18ml of Amiodarone Taj Pharma (two ampoules) in 500ml of 5% w/v Glucose. It should also be stressed that no other compounds are to be mixed with Amiodarone Taj Pharma infusion solution.

Amiodarone Taj Pharma should be administered solely in 5% w/v Glucose Intravenous Infusion.

Amiodarone Taj Pharma must not be mixed with other medicinal products in the same syringe.

Intravenous infusion:

The calculated dose is diluted with 250ml 5% w/v Glucose Intravenous Infusion. See section 4.2.

Intravenous injection:

150mg/3ml, 450mg/9ml, and  900mg/18ml (corresponding to 3-6ml Amiodarone Taj Pharma) is diluted with 10-20ml 5% w/v Glucose Intravenous Infusion. See section 4.2.

Any unused product or waste material should be disposed of in accordance with local requirements.

Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)Monday through Saturday 9:00 a.m. to 7:00 p.m. EST E-mail: tajgroup@tajpharma.com

Amiodarone Hydrochloride for Injection USP 900mg/18ml Taj Pharma

Read all of this lea­et carefully before you start using 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, pharmacist or nurse.
  • If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this lea­et. See section 4.

What is in this lea­et:

  1. What Amiodarone Taj Pharma is and what it is used for
  2. What you need to know before you are given Amiodarone Taj Pharma
  3. How you will be given Amiodarone Taj Pharma
  4. Possible side effects
  5. How to store Amiodarone Taj Pharma
  6. Contents of the pack and other information

1. What Amiodarone Taj Pharma is and what it is used for

Amiodarone Taj Pharma 150mg/3ml Concentrate for Solution for
Injection/Infusion (called Amiodarone Taj Pharma in this lea­et) contains a medicine called Amiodarone Taj Pharma hydrochloride. This belongs to a group of medicines called anti-arrhythmics.

It works by controlling the uneven beating of your heart (called ‘arrhythmias’). Having the injection helps your heartbeat to return to normal.
Amiodarone Taj Pharma is normally only given in a hospital when a quick response is needed or when tablets cannot be given. Amiodarone Taj Pharma can be used to:

  • Treat uneven heartbeats where other medicines either have not worked or cannot be used
  • Treat an illness called Wolff-Parkinson-White Syndrome. This is where your heart beats unusually fast
  • Treat other types of fast or uneven heartbeats known as ‘atrial ­utter’ or ‘atrial ‑brillation’. Amiodarone Taj Pharma is used only when other medicines cannot be used
  • Treat fast heartbeats which may happen suddenly and may be uneven. Amiodarone Taj Pharma is used only when other medicines cannot be used
  1. What you need to know before you are given Amiodarone Taj Pharma

Do not use this medicine and tell your doctor, pharmacist or nurse if you:

  • are allergic to iodine, Amiodarone Taj Pharma, or any of the other ingredients of Amiodarone Taj Pharma (listed in Section 6 below). Signs of an allergic reaction include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue
  • have a slower than usual heartbeat (called ‘sinus bradycardia’) or an illness called ‘sino-atrial’ heart block
  • have any other problems with your heartbeat and do not have a pacemaker ‑tted
  • have or have previously had thyroid problems. Your doctor should test your thyroid before giving you this medicine
  • have severe breathing problems
  • have serious blood circulation problems
  • have very low blood pressure
  • are taking certain other medicines which could affect your heartbeat (see ‘Other medicines and Amiodarone Taj Pharma’ below) • are pregnant or breast-feeding (see ‘Pregnancy and breast-feeding’ below) This product must not be given to children, premature babies or neonates. Do not use this medicine if any of the above apply to you. If you are not sure, talk to your doctor, pharmacist or nurse before using Amiodarone Taj Pharma.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before you are given Amiodarone Taj Pharma.

Amiodarone Taj Pharma should be given with care if you:

  • have a weak heart (‘cardiomyopathy’) or heart failure
  • have low blood pressure
  • are an elderly person (> 60 years)
  • have liver problems
  • require oxygen treatment
  • are to undergo a general anaesthetic
  • have any problems with your eyesight. This includes an illness called ‘optic neuritis’
  • are taking certain other medicines – for list of medicines see section “Other medicines and Amiodarone Taj Pharma” below

If you are not sure if any of the above apply to you, talk to your doctor, nurse or pharmacist before having Amiodarone Taj Pharma.

Children

This medicine should not be given to neonates, infants and children up to 3 years old.

Other medicines and Amiodarone Taj Pharma

Tell your doctor, pharmacist or nurse if you are taking or have recently taken or might take any other medicines. This is because Amiodarone Taj Pharma can affect the way some other medicines work. Also some medicines can affect the way

Amiodarone Taj Pharma works.
In particular, do not take this medicine and tell your doctor, if you are taking:

  • Medicines which may cause heart rhythm disturbance (called torsades de pointes):
  • other medicines to treat irregular heartbeat (such as
  • Quinidine, procainamide, disopyramide, sotalol or Bretylium)
  • some antibiotics (such as erythromycin injection, Co-trimoxazole, pentamidine injection)
  • Medicines for schizophrenia (such as chlorpromazine, Thioridazine, Fluphenazine, pimozide, haloperidol, Amisulpride or Sertindole)
  • Medicines for other mental illnesses (such as lithium, Doxepin, maprotiline or amitriptyline)
  • Medicines for malaria (such as quinine, Mefloquine, Chloroquine or halofantrine)
  • medicines used for hay fever, rashes or other allergies called antihistamines (such as terfenadine, astemizole or mizolastine)
  • Gastrointestinal agents e.g. Cisapride, droperidol

Tell your doctor if you are taking any of the following medicines:

  • Medicines for heart problems called beta-blockers (such as propranolol)
  • Medicines called calcium channel blockers for chest pain (angina) or high blood pressure (such as diltiazem or verapamil)
  • Medicines for constipation (laxatives) such as bisacodyl or senna
  • Medicines for high cholesterol (statins) such as simvastatin or atorvastatin
  • Tetracosactrin (used in some blood tests or sometimes in the treatment of Crohn’s disease)
  • Drugs which may change the levels of potassium or magnesium in your blood e.g. diuretics (water tablets), steroid tablets
  • Monoamine oxidase inhibitors (medications used in high blood pressure)
  • Warfarin – used for thinning the blood. Your doctor should reduce your dose of warfarin and monitor your treatment closely
  • Digoxin – used for heart problems. Your doctor should monitor your treatment closely and may halve your dose of digoxin
  • Phenytoin – used to treat fits
  • Ciclosporin and tacrolimus – used to help prevent rejection of transplants
  • Medicines for impotence such as sildenafil, tadalafil or vardena‑l
  • Fentanyl – used for pain relief
  • Ergotamine – used for migraines
  • Midazolam – used to treat anxiety or to help you relax before surgery
  • Lidocaine – used as an anaesthetic

If you are not sure if any of the above apply to you, talk to your doctor, nurse or pharmacist before taking Amiodarone Taj Pharma.

Amiodarone Taj Pharma with food and drink

Do not drink grapefruit juice while taking this medicine. This is because drinking grapefruit juice while taking Amiodarone Taj Pharma can increase your chance of getting side effects.

You should limit the amount of alcohol you drink whilst being treated with this medicine.

Protect your skin from sunlight

Keep out of direct sunlight while taking this medicine and for a few months after you have ‑nished taking it. This is because your skin will become much more sensitive to the sun and may burn, tingle or severely blister if you do not take the following precautions:

  • Make sure you use high factor sun cream
  • Always wear a hat and clothes which cover your arms and legs

Pregnancy and breast-feeding

Do not take this medicine if

  • You are pregnant, might become pregnant or think you may be pregnant
  • You are breast-feeding or planning to breast feed

Your doctor will prescribe Amiodarone Taj Pharma only if he/she considers the bene‑t of treatment outweighs the risks during your pregnancy. Amiodarone Taj Pharma can be used during pregnancy in life-threatening circumstances only.

Driving and using machines

Your doctor will tell you how long to wait before driving a car or using machines after you are given this medicine.

Amiodarone Taj Pharma Injection contains:

  • Iodine: Amiodarone Taj Pharma Injection contains about 56mg of iodine in one ampoule of 3ml. Iodine is present in Amiodarone Taj Pharma hydrochloride, the medicine your infusion contains. Iodine can cause problems to your thyroid (see ‘Tests’ below)
  • Benzyl Alcohol: Amiodarone Taj Pharma Injection contains benzyl alcohol. It must not be given to premature or newborn babies. Benzyl alcohol may cause toxic reactions and allergic reactions in infants and children up to 3 years old.
  1. How you will be given Amiodarone Taj Pharma

Your doctor or nurse will normally give you Amiodarone Taj Pharma.

This is because it needs to be given as an infusion into your vein in the hospital where the doctor can monitor your progress.

Using this medicine

  • This medicine will be diluted before it is given to you
  • Your doctor will change you over to Amiodarone Taj Pharma tablets as soon as possible
  • If you feel the effect of your medicine is too weak or too strong, tell your doctor, nurse or pharmacist

If you are not sure why you are receiving Amiodarone Taj Pharma or have any questions about how much Amiodarone Taj Pharma is being given to you, speak to your doctor, pharmacist or nurse.

How much will be given to you

Your doctor will decide how much to give you depending on your illness.
Adults (including elderly)
Starting dose

The standard recommended dose is 5mg/kg bodyweight.However, this may vary depending upon your age and how well you respond to treatment. This medicine will be diluted using 5% glucose solution before it is given to you over a period of 20 minutes to 2 hours. It will be given slowly, usually via a drip into a vein in your arm or chest.

Depending on your response, you may be given further infusions up to 1200mg (approximately 15mg/kg bodyweight) in up to 500ml 5% glucose per 24 hours.

Maintenance dose

10 – 20mg per kg bodyweight in physiological glucose solution can be given every 24 hours (on average 600 to 800mg/ 24 hours up to a maximum of 1200mg/ 24 hours, equivalent to 4-5 ampoules, maximum 8 ampoules) for a few days. In some conditions the medicine may be given as a slow injection of 150-300mg in 10-20ml 5% glucose over a minimum of 3 minutes. If Amiodarone Taj Pharma is given in this way you will be closely monitored. As soon as an adequate response has been obtained using intravenous treatment, you may be switched to oral treatment.

Elderly patients should be closely monitored during treatment, particularly for thyroid function.

Use in children and adolescents

There are only limited data on the ef‑cacy and safety in children. Your doctor will decide on an appropriate dose.

Patients with liver and kidney problems

Although no dosage adjustment for patients with kidney or liver abnormalities has been de‑ned during chronic treatment with oral Amiodarone Taj Pharma, close clinical monitoring is prudent for elderly patients.

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

If you use more Amiodarone Taj Pharma than you should

Your doctor will carefully calculate how much Amiodarone Taj Pharma you should get. Therefore it is unlikely your doctor, nurse or pharmacist will give you too much of this medicine. But, if you think that you have been given too much or too little Amiodarone Taj Pharma, tell your doctor, nurse or pharmacist.

The following effects may happen: feeling dizzy, faint, sick, tired or confused; having an abnormally slow or fast heartbeat.
Too much Amiodarone Taj Pharma can damage the heart and liver.

If you forget to use Amiodarone Taj Pharma

Your doctor or nurse will have instructions on when to give you this medicine. It is unlikely that you will not be given the medicine as it has been prescribed. However, if you think you may have missed a dose, then talk to your doctor or nurse.

If you stop using Amiodarone Taj Pharma

It is important for you to keep having Amiodarone Taj Pharma until your doctor decides to stop. If you stop having this medicine the uneven heartbeats may come back. This could be dangerous.

Tests

Your doctor may do regular thyroid tests while you are taking this medicine. This is because Amiodarone Taj Pharma contains iodine which can cause problems to your thyroid.

Your doctor may also do other regular tests such as blood tests, chest X-rays, ECG (electrical test of your heartbeat) and eye tests both before and while you are having Amiodarone Taj Pharma.

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

  1. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Amiodarone Taj Pharma may stay in your blood for up to a month after stopping treatment.

You may still get side effects in this time.

If any of the following happen, tell your doctor immediately. These are very serious side effects and you may need urgent medical attention.

  • breathing difficulties
  • chest pain
  • severe allergic reaction – you may experience a sudden itchy rash (hives), swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing), you may feel you are going to faint and there may be in­ammation of some of your blood vessels.

If you experience any of the following tell your doctor as soon as possible.

Very common (may affect more than 1 in 10 people)

  • blurred eyesight or seeing a coloured halo in dazzling light
  • burning more easily in the sun (see ‘Protect your skin from sunlight’ in Section 2)

Common (may affect up to 1 in 10 people)

  • itchy, red rash (eczema)
  • generally moderate slow heart rate
  • decrease in blood pressure
  • local injection site reactions including swelling, pain, redness, infection, and pigmentation changes (blue or grey marks on parts of your skin exposed to sunlight, especially the face)
  • feeling extremely restless or agitated, weight loss, increased sweating and being unable to stand the heat. These could be signs of an illness called ‘hyper-thyroidism’
  • feeling extremely tired, weak or run-down, weight gain, being unable to stand the cold, constipation and aching muscles. These could be signs of an illness called hypo-thyroidism
  • trembling when you move your arms or legs
  • muscle weakness
  • nightmares
  • problems sleeping

Uncommon (may affect up to 1 in 100 people)

  • feeling numb or weak, tingling or burning feelings in any part of your body
  • dizziness

Rare (may affect up to 1 in 1,000 people)

  • the excipient benzyl alcohol may cause hypersensitivity reactions

Very rare (may affect up to 1 in 10,000 people)

  • chest pain or palpitations, or abnormal heart rhythm
  • nausea
  • liver disorders
  • generalised allergic reactions such as swelling of the face, lips and/or tongue, shortness of breath,
  • headaches, breathing difficulties (with or without fever)
  • inability to breathe
  • hot flushes
  • sweating
  • red, scaly patches of skin, loss of hair or loosening of nails (called ‘exfoliative dermatitis’)
  • loss of eyesight in one eye or your eyesight becomes dim and colourless. Your eyes may feel sore or tender and feel painful to move. This could be an illness called ‘optic neuropathy or neuritis’
  • skin rash
  • skin redness during radio-therapy
  • moving unsteadily or staggering, slurred or slow speech
  • headache (which is usually worse in the morning or happens after coughing or straining), feeling sick (nausea), fits, fainting, eyesight problems or confusion can These could be signs of problems with your brain
  • balance problems, feeling dizzy (vertigo)
  • headache
  • feeling unwell, confused or weak, feeling sick (nausea), loss of appetite, feeling irritable. This could be an illness called ‘syndrome of inappropriate anti-diuretic hormone secretion’ (SIADH).

Not known (frequency cannot be estimated from the available data)

  • seeing or hearing things that are not real (hallucinations)
  • sudden inflammation of the pancreas (pancreatitis (acute)); confusion (delirium); life threatening skin reactions characterised by rash, blisters, peeling skin and pain (toxic epidermal necrolysis (TEN), StevensJohnson syndrome (SJS), bullous dermatitis, Drug reaction with eosinophilia and systematic symptoms (DRESS)).

Reporting of side effects

If you get any side effects talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.
By reporting side effects you can help provide more information on the safety of this medicine.

  1. How to store Amiodarone Taj Pharma

This medicine will be kept by your doctor or pharmacist in a safe place where children cannot see or reach it.

Do not use Amiodarone Taj Pharma after the expiry date which is stated on the carton and label after EXP. The expiry date refers to the last day of that month.

Do not store above 25°C. Do not refrigerate or freeze.

Storage at low temperature could cause the formation of precipitate. Store in the original container.  Do not use unless solution is clear. Only clear solutions free of particles should be used. Reject any portion not used immediately after the opening of the ampoule. After dilution, use the solution immediately and reject any portion unused.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

  1. Contents of the pack and other information

What Amiodarone Taj Pharma contains

The acitve substance is Amiodarone Taj Pharma hydrochloride
The other ingredients are Polysorbate 80, Benzyl alcohol, Hydrochloride acid or Sodium Hydroxide, Water for injection.

What Amiodarone Taj Pharma looks like and contents of the pack

Amiodarone Taj Pharma is a pale yellow solution and is available as 3ml, 9ml, and 18ml glass ampoules in cartons of 5 or 10 units.

Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)Monday through Saturday 9:00 a.m. to 7:00 p.m. EST E-mail: tajgroup@tajpharma.com