AMIODARONE HYDROCHLORIDE

Treatment should be initiated and normally monitored only under hospital or specialist supervision. Amiodarone hydrochloride should only be used when facilities exist for cardiac monitoring, defibrillation, and cardiac pacing. Thyroid function test should be performed where appropriate prior to therapy in all patients.

Posology 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 glucose 5%. 4). In extreme clinical emergency the drug may, at the discretion of the clinician, be given as a slow intravenous injection of 150-300mg in 10-20ml glucose 5% over a minimum of 3 minutes.

This should not be repeated for at least 15 minutes. g. 4). e. 200mg three times a day). Amiodarone hydrochloride should then be phased out gradually. Paediatric population The safety and efficacy of amiodarone in children and adolescents has not been established.

2. Due to the presence of benzyl alcohol, intravenous Amiodarone Hydrochloride 50 mg/ml Concentrate for Solution for Injection/Infusion 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. 8). Cardiopulmonary resuscitation The recommended dose for ventricular fibrillations/pulseless ventricular tachycardia resistant to defibrillation is 300 mg (or 5 mg/kg body-weight) diluted in 20 ml glucose 5% and rapidly injected.

5 mg/kg body-weight) IV dose may be considered if ventricular fibrillation persists. g. in an intensive care unit. Method of administration Intravenous use. 6.

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 - In patients taking amiodarone there have been incidental findings of bone marrow granulomas.

The clinical significance of this is unknown - Neutropenia - Agranulocyto sis Immune system disorders • Anaphylactic shock. Angioneurotic oedema (Quincke’s 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) oedema) Endocrine disorders Syndrome of inappropriate antidiuretic hormone secretion (SIADH).

4). -Hypothyroidism. Psychiatric disorders Libido decreased - Delirium (including confusion). - Hallucination Nervous system disorders Extrapyramid al tremor. Peripheral sensorimotor neuropathy and/or myopathy, usually reversible on withdrawal of the drug.

- Benign intracranial hypertension (pseudo-tumour cerebri). - 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 may be associated with colored halos in dazzling light or blurred vision.

They usually regress 6-12 months after discontinuatio n of amiodarone hydrochloride. 4). Cardiac disorders Dose- dependent bradycardia. 4) 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) discontinuation of the treatment.

5). - Conduction disturbances (sinoatrial block, AV block). Vascular disorders Hypotension 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 too rapid administration (bolus injection).

Hot Flushes. 4). - Acute adult respiratory distress syndrome, sometimes with fatal sequelae. - Bronchospasm and/or apnoea 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) in patients with serious respiratory problems, especially patients with asthma.

Gastrointesti nal disorders Nausea. Pancreatitis (acute). 5 to 3 times above normal) at the start of treatment, which is often transient in nature and resolves spontaneously upon lowering the dose. 4). Skin and subcutaneou s tissue disorders Eczema.

Sweating. - Urticaria. - Severe skin reaction as toxic epidermal necrolysis (TEN)/Stevens- Johnson syndrome (SJS), bullous dermatitis and Drug reaction with eosinophilia and systematic symptoms (DRESS). Musculoskel Back pain. 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) etal and Connective Tissue Disorders Reproductiv e system and breast disorders Libido decreased General disorders and administrati on site conditions At the site of injection or infusion: pain, erythema, oedema, necrosis, extravasation, infiltration, inflammation, induration, thrombophleb itis, phlebitis, cellulitis, infection, pigmentation changes.

The excipient benzyl alcohol may cause hypersensitiv ity reactions. 4). A few rare cases with various clinical symptoms, indicative of hypersensitivity reactions, have been reported: vasculitis, reduced renal function with a rise in creatinine levels, thrombocytopenia, anaphylaxis.

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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

2 mg/ml). Benzyl alcohol may cause toxic and allergic reactions. The minimum amount of benzyl alcohol at which toxicity may occur is not known with an increased risk in young children due to accumulation. The administration of medications containing benzyl alcohol to newborns or premature neonates has been associated with serious adverse events and a fatal “Gasping Syndrome” (symptoms include a striking onset of gasping syndrome, hypotension, bradycardia and cardio-vascular collapse).

2). 6). High volumes of medications containing benzyl alcohol should be used with caution and only if necessary, especially in subjects with liver or kidney impairment because of the risk of accumulation and toxicity (metabolic acidosis).

Administration:

Amiodarone hydrochloride should only be used in a special care unit under continuous monitoring (ECG and blood pressure). 8). Circulatory collapse may be precipitated by too rapid administration or overdosage (atropine has been used successfully in such patients presenting with bradycardia).

8). When repeated or continuous infusion is anticipated, administration by a central venous catheter is recommended. Amiodarone should not be mixed with other preparations in the same syringe and should not be injected with other preparations in the same line.

2). When given by infusion amiodarone hydrochloride may reduce drop size and, if appropriate, adjustments should be made to the rate of infusion. 5): Before surgery, the anaesthetist should be informed that the patient is taking amiodarone.

Reports of crystallisation have been received for hameln Amiodarone Hydrochloride 50 mg/ml Concentrate for Solution for Injection/Infusion: • Inspect each ampoule and check for crystalline content prior to administration. The solution should only be used if it is clear, free from particles and the container is undamaged and intact.

• Consider the use of in-line filters as an additional precautionary measure. 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. Severe bradycardia and heart block after sofosbuvir 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 HCV treatment. Amiodarone should only be used in patients on 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 on sofosbuvir- containing regimen.

All patients receiving amiodarone in combination with sofosbuvir-containing regimen should be warned of the symptoms of bradycardia and heart block and should be advised to seek medical advice urgently should they experience them.

Primary graft dysfunction (PGD) post cardiac transplant:

In retrospective studies, amiodarone use in the transplant recipient prior to heart transplant has been associated with an increased risk of 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 […]

1. ) - Due to the presence of benzyl alcohol, intravenous Amiodarone Hydrochloride 50 mg/ml Concentrate for Solution for Injection/Infusion is contraindicated in neonates. - Severe respiratory failure, circulatory collapse, or severe arterial hypotension; hypotension, heart failure and cardiomyopathy are also contraindications when using Amiodarone Hydrochloride 50 mg/ml as a bolus injection.

4). - Sinus bradycardia, sino-atrial heart block and sick sinus syndrome in patients without a pacemaker. In patients with severe conduction disturbances (high grade AV block, bifascicular or trifascicular block) or sinus node disease, amiodarone should be used only in specialized units in conjunction with a pacemaker.

5). - Pregnancy and lactation. 6. The above contraindications do not apply to the use of amiodarone hydrochloride for cardiopulmonary resuscitation of shock-resistant ventricular fibrillation.