AMIODARONE HYDROCHLORIDE

Treatment should be initiated and normally monitored only under hospital or specialist supervision when facilities for cardiac monitoring, defibrillation, and cardiac pacing are available. Amiodarone Hydrochloride 20 mg/ml solution for infusion should be administered by health care professionals who are experienced in the treatment of serious cardiac arrhythmias and are thoroughly familiar with the risks and benefits of the use of amiodarone via intravenous routes.

Thyroid function test should be performed where appropriate prior to therapy in all patients. Protecting skin from sunlight is required during therapy as patients receiving amiodarone can become unduly sensitive to sunlight, which may persist after several months of discontinuation of therapy.

4). Table 1 Recommended initial loading doses of amiodarone hydrochloride at 5 mg per kg of body weight and corresponding infusion rates. 5 The effect occurs within a few minutes and decreases gradually. Therefore, it must be followed by a maintenance infusion.

Maintenance infusion:

Administer 10 - 20 mg per kg body weight every 24 hours (on average 600 to 800 mg/ 24 hours up to a maximum of 1200 mg/ 24 hours) for a few days (see Table 2). Table 2 Recommended maintenance dose of amiodarone hydrochloride. 04ml/ min ] Changeover from intravenous to oral therapy: Amiodarone Hydrochloride 20 mg/ml solution for infusion is normally administered only to initiate therapy, for no longer than one week.

e. 200 mg three times a day). Amiodarone hydrochloride should then be phased out gradually. Paediatric population The safety and efficacy of amiodarone in neonates, children and adolescents has not been established. 2. Elderly patients 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. 8). g. in an intensive care unit. Method of administration Intravenous infusion only.

g. syringe driver/syringe pump) capable of accurately and consistently delivering the specified volume at a strictly controlled rate of infusion. Amiodarone Hydrochloride 20 mg/ml solution for infusion should not be diluted before use; it is supplied ready to use.

Inadvertent dilution of Amiodarone Hydrochloride 20 mg/ml solution for infusion could lead to under-dosing of the patients and decreased therapeutic response. Amiodarone Hydrochloride 20 mg/ml solution for infusion must not be administered as a direct IV (bolus) injection.

Intravenous amiodarone concentrations exceeding 2 mg/ml, such as Amiodarone Hydrochloride 20 mg/ml solution for infusion, containing 20 mg/ml, are associated with peripheral vein irritation/phlebitis. 4). 9% infusion fluids. In situations where it may be urgently required to administer concomitant medicinal products through a central line, careful consideration should be given to the compatibility of the medicinal products administered and the type of vascular access device used.

During maintenance infusion, the product should be protected from light.

The most common adverse drug effects reported with intravenous amiodarone hydrochloride are infusion phlebitis, bradycardia, and hypotension.

Table 1:

Frequency of the adverse reaction System Organ Class Very common (≥ 1/10) Common (≥ 1/100 to <1/10) Uncommon (≥ 1/1,000 to <1/100) Rare (≥ 1/10,000 to<1/1,000) Very rare (<1/10,000) Not known (cannot be estimated from the available data) Blood and lymphatic system disorders Haemolytic or aplastic anaemia -In patients taking amiodarone there have been incidental findings of bone marrow granulomas.

The clinical significance of this is unknown. 4) -Hypothyroidism Syndrome of inappropriate antidiuretic hormone secretion (SIADH) - Psychiatric disorders Libido decreased -Delirium (including confusion) - Hallucination Reproductiv e system and breast disorders Epididymitis Sexual dysfunction Nervous system disorders -Extrapyramidal tremor -Nightmares -Sleep disturbances -Peripheral sensorimotor neuropathy and/or myopathy, usually reversible on withdrawal of the drug -Dizziness -Impaired coordination -Paresthesia - Benign intracranial hypertension (pseudo- tumour cerebri) - Cerebral ataxia - Headache Eye disorders Microdeposits at the anterior surface of the cornea are found in almost every patient, which are usually limited to the area below the pupil.

They Optic neuropathy/ne uritis that may progress to blindness. System Organ Class Very common (≥ 1/10) Common (≥ 1/100 to <1/10) Uncommon (≥ 1/1,000 to <1/100) Rare (≥ 1/10,000 to<1/1,000) Very rare (<1/10,000) Not known (cannot be estimated from the available data) may be associated with colored halos in dazzling light or blurred vision.

They usually regress 6-12 months after discontinuatio n of amiodarone hydrochloride. Cardiac disorders - Dose- dependent bradycardia - Conduction disturbances (sinoatrial block, AV block); in individual cases the occurrence of asystole was observed.

5) Severe bradycardia (in cases of sinus node dysfunction and in the elderly) or (more rarely) sinus arrest: this may necessitate discontinuatio n of the treatment. 5) - Isolated cases of ventricular fibrillation/ flutter have been described.

Vascular disorders - Hypote nsion and increased heart rate immediately following injection. These are generally moderate and transient in nature. Cases of severe hypotension or shock have been reported following overdose or Vasculitis Hot Flushes System Organ Class Very common (≥ 1/10) Common (≥ 1/100 to <1/10) Uncommon (≥ 1/1,000 to <1/100) Rare (≥ 1/10,000 to<1/1,000) Very rare (<1/10,000) Not known (cannot be estimated from the available data) too rapid administration (bolus injection).

4). 4). -Exanthema -Exfoliative dermatitis -Alopecia -Sweating syndrome (SJS), bullous dermatitis and Drug reaction with eosinophilia and systematic symptoms (DRESS) Musculoskel etal and Connective Tissue Disorders Muscle weakness Back pain General disorders and administrati on site conditions At the site of injection or infusion: pain, erythema, oedema, necrosis, extravasation, infiltration, inflammation, induration, thrombophlebiti s, phlebitis, cellulitis, infection, pigmentation changes Fatigue The excipient polysorbate 80 may cause allergic reactions.

4) Rarely, polysorbates can cause severe allergic reactions (dyspnoea, swelling, dizziness), and hepatotoxicity (abrupt elevation of liver enzymes). g. hypotension, cardiac depression). 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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Primary Graft Dysfunction post cardiac transplant In retrospective studies, amiodarone use in the transplant recipient prior to heart transplant has been associated with an increased risk of primary graft dysfunction (PGD). 8). Severe PGD may be irreversible.

For patients who are on the heart transplant waiting list, consideration should be given to use an alternative antiarrhythmic drug as early as possible before transplant. Amiodarone Hydrochloride 20 mg/ml solution for infusion contains polysorbate 80 (see section 2) Polysorbates may cause hypotension and heart rate changes (potential cardiotoxicity).

The risk of severe hypotension can be minimised by slowing down the infusion. Electrophysiological studies show cardiac depression in dogs and inhibition of hERG currents by polysorbates in vitro. The potential for torsade de pointes in humans is unknown.

8). 875 ml of solution for infusion/kg) in adults and children. However, it needs to be taken into consideration that amiodarone itself can cause hepatotoxicity. Administration Amiodarone hydrochloride should only be used in a special care unit under continuous monitoring (ECG and blood pressure) where facilities for cardiac pacing and defibrillation exist.

Circulatory collapse may be precipitated by too rapid administration or overdosage. Intravenous amiodarone concentrations exceeding 2 mg/ml, such as Amiodarone Hydrochloride 20 mg/ml solution for infusion ,containing 20 mg/ml, are associated with peripheral vein irritation/phlebitis.

Amiodarone Hydrochloride must be administered via a central line. Monitoring Cardiac function (ECG) monitoring should be facilitated and serum potassium levels, liver, thyroid, lung function tests, and chest x-ray should be performed before initiating of treatment.

Liver enzymes should be checked at regular intervals during treatment. Careful monitoring for signs of extravasation (following local guidelines) of the Central Venous Access Device and the surrounding area, should be undertaken both during and following an infusion.

Prolonged phototoxicity Because of the possibility of phototoxic reaction, sunlight exposure should be avoided during and after discontinuation of therapy with amiodarone; this also applies to UV light and solariums/sunbeds. If this cannot be avoided, the uncovered skin areas, especially the face, should be protected by topical preparations with a high sun protection factor.

Even after discontinuation of Amiodarone Hydrochloride 20 mg/ml solution for infusion, sun protection is still required for several months due to extensive distribution and long half-life of amiodarone in the body. 3). Amiodarone 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.

8). Despite QT interval prolongation, amiodarone exhibits a low torsadogenic activity. 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 cardiac glycoside therapy.

In these circumstances, amiodarone hydrochloride treatment should be withdrawn. If necessary beta-adrenostimulants or glucagon may be given. Because of the long half-life of amiodarone, if bradycardia is severe and symptomatic the insertion of a pacemaker should be considered.

The pharmacological action of amiodarone 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. Excessive QT prolongation may increase the risk of torsade de pointes arrhythmia, therefore patients with pre- existing QT prolongation should be carefully monitored.

Severe bradycardia and heart block Life-threatening cases of bradycardia and heart block have been observed when sofosbuvir-containing regimens are used in combination with amiodarone. Bradycardia has generally occurred within hours to days, but later cases have been mostly observed up to 2 weeks after initiating Hepatitis C Virus (HCV) treatment.

Amiodarone should only be used in patients on a sofosbuvir- containing regimen when other alternative anti-arrhythmic treatments are not tolerated or are contraindicated. Should concomitant use of amiodarone be considered necessary, it is recommended that patients undergo cardiac monitoring in an in-patient setting for the first 48 hours of coadministration, after which outpatient or self-monitoring of the heart rate should occur on a daily basis through at least the first 2 weeks of treatment.

Due to the long half-life of amiodarone, cardiac monitoring as outlined above should also be carried out for patients who have discontinued amiodarone within the past few months and are to be initiated […]

4); - Sinus bradycardia, sino-atrial heart block and sick sinus syndrome in patients without a pacemaker. 5); - Iodine allergy (one vial contains approximately 372 mg iodine); - Pregnancy and lactation. 6; - Cardiopulmonary resuscitation of ventricular fibrillation /pulseless ventricular tachycardia resistant to defibrillation as Amiodarone Hydrochloride 20 mg/ml solution for infusion is not intended for direct (bolus) IV injection.