Amiodarone. Traffic light classification- Amber 2 Information sheet for Primary Care Prescribers

Transcription

1 Amiodarone Traffic light classification- Amber 2 Information sheet for Primary Care Prescribers Licensed Indications Tachyarrhythmias associated with Wolff-Parkinson-White syndrome All types of tachyarrhythmias including paroxysmal, supraventricular, nodal and ventricular tachycardias; atrial flutter and fibrillation; ventricular fibrillation; when other drugs cannot be used. Therapeutic Summary Amiodarone is indicated for the control of arrhythmias where other drugs have been unsuccessful or deemed inappropriate. Medicines Initiation Amiodarone is suitable for prescribing in primary care following specialist recommendation or initiation. Products available Medication is available as generic tablets (100mg, 200mg). Also available branded as Cordarone X tablets. Dosages and route of administration When given orally amiodarone is given as 200mg three times a day for 1 week, then 200mg twice a day for 1 week, then 200mg daily or the minimum required to control the arrhythmia. Duration of treatment Treatment is potentially lifelong. Monitoring Requirements and Responsibilities for primary care In warfarinised patients, more frequent monitoring of INR is required during initiation or dose change of amiodarone until INR is stable and for at least 6 weeks after stopping amiodarone treatment; initially weekly for the first 7 weeks of treatment or until INR stable. The dose of warfarin required may be around one-third less than without amiodarone treatment. Before starting amiodarone it is recommended to perform an ECG and serum potassium measurement (as part of U&E measurement). Amiodarone may increase the defibrillation threshold and/or pacing threshold in patients with an implantable cardioverter, defibrillator or pacemaker, which may adversely affect the efficacy of the device. Regular tests are recommended to ensure the proper function of the device after initiation of treatment or change in posology.

2 Frequency Required tests TSH* LFT U&E Chest X ray ECG Opthalm -ological 6 monthly 12 monthly ** Also ask about breathlessness and non-productive cough, relating to possible pulmonary toxicity, at each review visit *TSH should be measured every 6 months during treatment and for up to 12 months following discontinuation (amiodarone has a half-life of 20 to 100 days). Serum TSH should be measured when thyroid dysfunction is suspected. ** And any time new or worsening visual symptoms occur (common side effect is a blue halo effect when looking into bright lights at night time). Encourage patient to attend optometrist annually. Explicit criteria for review and discontinuation of the medicine Isolated cases of acute liver disorders with elevated serum transaminases and/or jaundice may occur; in such cases treatment should be discontinued. Treatment should be discontinued in cases of onset of 2 nd or 3 rd degree A-V block, sino-atrial block, or bifascicular block. 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 should be withdrawn. Amiodarone can cause hypothyroidism. The decision to discontinue amiodarone should be made by a specialist, as in life-threatening situations amiodarone therapy can be continued, in combination with levothyroxine. Appearance of optic neuropathy and/or optic neuritis requires amiodarone withdrawal due to the potential progression to blindness. Contraindications Contraindicated during pregnancy. Excreted in breast milk in significant quantities, breast-feeding is contraindicated. Sinus bradycardia and sino-atrial heart block: In patients with severe conduction disturbances (high grade AV block, bifascicular or trifascicular block) or sinus node disease, amiodarone should be used only in conjunction with a pacemaker. Evidence of history of thyroid dysfunction: Thyroid function tests should be performed prior to therapy in all patients. Known hypersensitivity to iodine or to amiodarone, or any of the excipients. Contraindicated in drugs where combinations with amiodarone may induce Torsades de Pointe. Patients with the rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take amiodarone Precautions (see SPC section 4.4 for expanded information) Anaesthesia caution is advised in patients undergoing general anaesthesia, and patients receiving high-dose oxygen therapy. Before surgery, the anesthetist should be informed that the patient is taking amiodarone.

3 High dosage - high doses of amiodarone 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 treatment should be withdrawn. Heart failure amiodarone is not contra-indicated in patients with latent or manifest heart failure but caution should be exercised as heart failure may be worsened. ECG changes QT interval lengthening has been observed. This is indicative of pharmacological action and does not reflect toxicity. Treatment should be discontinued in cases of onset of second or third-degree AV block. Arrhythmias Onset of new arrythmias or worsening of pre-existing arrhythmias has been observed. Pro-arrhythmic effects generally occur in the context of drug interactions and/or electrolyte disorders. Hepatic effects May be associated with a variety of hepatic effects. Monitor liver function before treatment and 6 monthly thereafter. Refer to SPC for interpretation of changes in LFTs. Eye disorders ophthalmological is recommended annually, unless blurred or decreased vision occurs in which case a complete ophthalmologic should be performed promptly. Respiratory, thoracic and mediastinal disorders Pulmonary toxicity is a particular concern and if suspected (see SPC for potential presentations), chest X rays should be repeated and associated with lung function tests and measurement of transitional factor. Pulmonary toxicity is usually reversible following withdrawal but some patients may deteriorate despite this. Endocrine disorders May induce hypo- or hyperthyroidism, particularly in patients with a history of such disorders. See SPC for further details. Nervous system disorders May induce peripheral sensorimotor neuropathy and/or myopathy. Skin & subcutaneous tissue disorders Hypersensitivity to sunlight may occur in patients taking amiodarone advice patients to avoid exposure to the sun or to use adequate protection. Elderly In the elderly, heart rate may decrease markedly. The risks of thyroid dysfunction during amiodarone therapy are also greater. Cardiac disorders Amiodarone may increase the defibrillation threshold and/or pacing threshold in patients with an implantable cardioverter defibrillator or pacemaker, which may adversely affect the efficacy of the device. Clinically relevant medicine interactions and their management Grapefruit juice inhibits cytochrome P450 3A4 and may increase the plasma concentration of amiodarone, so should be avoided during treatment with amiodarone. Drugs which have significant interactions with amiodarone include warfarin, digoxin, phenytoin, fluoroquinolones and any drugs which prolong the QT interval. Amiodarone increases the plasma concentration of highly protein bound drugs, such as oral anticoagulants and phenytoin. Warfarin dose should be reduced, more frequently monitored required (for details see monitoring requirements page 1) Phenytoin Dose should be reduced if signs of overdose appear, plasma levels may be measured.

4 Digoxin Amiodarone may increase plasma digoxin levels, resulting in signs and symptoms associated with digoxin toxicity. Clinical, ECG and biological monitoring is required and a reduction of digoxin dosage by half may be necessary. Combined therapy with drugs known to prolong the QT interval is contraindicated, such as: o Class 1a anti-arrhythmics e.g. quinidne, procainamide, disopyramide o Class III anti-arrhythmics e.g. sotalol, bretylium o Intravenous erythromycin, co-trimoxazole or pentamidine injection o Some anti-psychotics e.g. chlorpromazine, thioridazine, fluphenazine, pimozide, haloperidol, amisulpride and sertinadole o Lithium and tricyclic anti-depressants o Certain antihistamines e.g. quinine, mefloquine, chloroquine, halofantrine o Moxifloxacin Combination with the following drugs is not recommended; o Beta blockers, and certain calcium channel inhibitors potentiation of negative chronotropic properties o Stimulant laxatives which may cause hypokalaemia Caution should be exercised in drugs which may cause hypokalaemia and/or hypomagnesaemia. In the case of hypokalaemia (increasing the risk of Torsades de Pointe), corrective action should be taken and QT interval monitored. In the case of Torsades de Pointe, anti-arrhythmic agents should not be given; pacing may be instituted and IV magnesium may be used. Anaesthesia Caution is advised; inform anaesthetist Fluoroquinolones Rare reports of QTc prolongation, concomitant use should be avoided. Flecainide Amiodarone increases plasma levels by inhibiting CYP2D6. flecainide dose may be reduced by 50%. Drugs metabolised by cytochrome P450 3A4 e.g. ciclosporin, lidocaine, tacrolimus, sildenafil, fentanyl, midazolam,ergotamine and statins may reach higher concentrations if co-administered with amiodarone, which may lead to possible toxicity. Simvastatin has been associated with reports of myopathy/rhabdomyolysis pravastatin should be preferred. Amiodarone has the potential to inhibit CYP 1A2, CYP 2C19, CYP 2D6. It will increase the plasma concentration of drugs whose metabolism is dependent on these isoenzymes.

5 Common Adverse effects Adverse effect Pulmonary toxicity (suggested by new or worsening cough and/or shortness of breath) Frequency Investigation & % Diagnosis 2 to 17 CXR and ECG to exclude alternative diagnoses Treatment If pulmonary toxicity is suspected: refer urgently to initiating cardiologist or respiratory physician. Hyperthyroidism 2 Free T4, TSH If normal, continue and reassess in 6 months. If deranged, stop and refer immediately to initiating specialist. Hypothyroidism 6 Free T4, TSH If normal, continue and reassess in 6 months. If deranged, stop and refer immediately to initiating specialist. Liver toxicity 1 LFT If normal, continue and reassess in 6 months. If deranged, stop and refer immediately to initiating specialist. Optic neuropathy 0.13 Ophthalmologic by an optician? If optic neuropathy/neuritis is suspected, refer urgently to ophthalmology and discuss the possibility of stopping amiodarone & alternative antiarrhythmic therapy with patient s cardiologist Pro-arrhythmia <1 ECG Stop amiodarone Tremor <10 History and clinical Peripheral Neuropathy Myopathy <1 History and clinical Bradycardia 2-4 Examination, ECG Reduce dosage or withdraw if possible Usually reversible on withdrawal of the drug If severe, discuss with cardiologist whether to stop amiodarone or insert pacemaker Reduce dosage Nausea, anorexia 30 History + Corneal microdeposits >90 Slit-lamp None Photosensitivity 4-9 History, Use sunblock Blue discolouration of <9 Examination Reduce dosage if possible skin Information given to patient Patient information leaflet available at Patient should be informed that they will require 6 monthly blood tests while taking the medication.

6 References NICE CG190 Atrial fibrillation: management, June UKMi Suggestions for drug monitoring in adults in primary care Sheffield Area prescribing group Shared care protocol for amiodarone, 4 th edition, January 2014 Full prescribing information is list in the summary of product characteristics for amiodarone, available at