Pharmacological properties
Pharmacodynamics. Amiodarone has antiarrhythmic and antianginal activity. According to the Vaughan-Williams classification, amiodarone belongs to class III antiarrhythmic agents. The mechanism of action of the drug is due to the blocking of ion channels of the cardiomyocyte membrane (mainly potassium, to a lesser extent sodium and calcium), as well as non-competitive blocking of α- and β-blockers. The antiarrhythmic effect of Cardiodarone is associated with the ability to increase the duration of the action potential (phase III) of cardiomyocytes and the effective refractory period, which is accompanied by a decrease in the automatism of the sinus node, a slowdown in AV conduction, and a decrease in myocardial excitability. The antianginal effect is achieved by reducing the need for myocardial oxygen (decrease in heart rate and afterload) and reducing coronary vascular resistance.
The hemodynamic and antiischemic effect of amiodarone is manifested in a moderate decrease in peripheral resistance and a decrease in heart rate (which leads to a decrease in oxygen consumption in the heart muscle), non-competitive blocking of the stimulating effect of α- and β-blockers, increased blood circulation in the coronary arteries due to a direct effect on the smooth muscles of the myocardial arteries, and ensuring stroke volume (due to a decrease in blood pressure in the aorta and peripheral vascular resistance).
Amiodarone has a mild negative inotropic effect. After intravenous administration, the predominant actions are sympatholytic (noncompetitive blocking of the stimulating effect of α- and β-blockers, as well as the effect of class II drugs) and calcium channel blockade (similar to the effect of class IV drugs). The predominant hemodynamic effect after intravenous administration of amiodarone is arterial hypotension, which is the result of a decrease in peripheral vascular resistance and negative inotropism. Usually, blood pressure decreases, but more severe hypotension can be avoided by reducing the infusion rate. The direct negative inotropic effect of intravenous administration of amiodarone is slight and temporary (it lasts for 1 hour after injection of a loading dose; up to 24 hours after infusion). As a rule, it does not cause a decrease in cardiac output, except in patients with left ventricular dysfunction, in whom cardiac output may be temporarily reduced. Tachycardia may occur during amiodarone administration, but it lasts about 5 minutes after administration. Bradycardia may occur 10-15 minutes after a loading dose injection, and may also occur during intravenous infusion. If infusion is continued for more than 3-5 days, bradycardia usually resolves on its own.
After intravenous injection of a loading dose, the antiarrhythmic effect appears within 1 hour after administration; with continued parenteral treatment (continued infusions), the maximum effect is achieved within 2 days.
Pharmacokinetics
Amiodarone is absorbed slowly and variably.
Oral administration. The volume of distribution is large (66 l/kg, i.e. 5000 l). Most of the amiodarone accumulates in adipose tissue and in organs that contain a significant amount of adipose tissue, such as the lungs, lymph nodes, heart, liver, pancreas, kidneys, muscle tissue and thyroid gland.
The average bioavailability of amiodarone is approximately 40-50%.
The maximum concentration in the blood plasma after oral administration of a single dose is reached after 2-10 hours. With prolonged treatment, the peak concentration is reached gradually, over several weeks or months.
T ½ after a single dose of amiodarone is on average 3.2-20.7 hours, and clearance is 0.14-0.69 l / min. With continued administration, T ½ of amiodarone is very long, namely: 13-103 days (on average - 53 ± 24 days). After discontinuation of treatment, elimination continues for several more months.
Parenteral administration. Bioavailability is approximately 30-60%. A rapid decrease in blood concentration occurs mainly through distribution in peripheral tissues. The volume of distribution varies from 40 to 130 l/kg of body weight. In the heart muscle, the maximum concentration is reached within a few minutes after i.v. injection. Amiodarone levels in the heart muscle are higher than in blood plasma. The metabolism of amiodarone occurs in the same way as after oral administration. T ½ of amiodarone after a single i.v. injection is on average 3.2-20.7 h, and after repeated i.v. infusion - approximately 50 days.
Amiodarone is metabolized in the liver, also partially in the intestine (in the intestinal mucosa). The main metabolic processes are deacetylation (in the liver) and N-dealkylation (in the intestine). Mono-N-desethylamiodarone (desethylamiodarone) is the main pharmacologically active metabolite of amiodarone.
The pharmacokinetics and pharmacodynamics of desethylamiodarone are similar to those of amiodarone.
Amiodarone is excreted via the gallbladder (with feces) and via the kidneys. Due to the fact that it is almost completely metabolized, it is found in feces and urine in insignificant amounts. Since urinary excretion is insignificant, dose adjustment is not necessary in patients with renal insufficiency.
Clinically, the antiarrhythmic effect is observed after approximately 7 days, and the maximum effect is after 15-30 days. After discontinuation of treatment, the therapeutic effect lasts for 10-30 days.
Amiodarone is not removed by hemodialysis or peritoneal dialysis.
Indication
Tablets. prevention of relapses:
- ventricular tachycardia and ventricular fibrillation, which pose a threat to the patient's life; treatment must be started in a hospital setting with constant monitoring of the patient's condition;
- symptomatic ventricular tachycardia, which leads to loss of working capacity;
- supraventricular tachycardia in patients with heart disease and other individuals requiring treatment for supraventricular tachycardia in whom treatment with other antiarrhythmic agents has been ineffective or contraindicated;
- ventricular fibrillation.
Treatment of supraventricular tachycardia:
- slowing or reducing atrial fibrillation or flutter;
- CHD and/or with functional dysfunction of the left ventricle.
Solution for injection
Treatment of paroxysmal cardiac arrhythmias (sinus tachycardia, supraventricular tachyarrhythmia, including atrial flutter and fibrillation of the flutter/flicker type, ventricular tachyarrhythmia, ventricular and supraventricular extrasystoles, WPW syndrome) and documented symptomatic cardiac arrhythmias.
Intravenous therapy with Cardiodarone is prescribed when it is necessary to obtain a rapid therapeutic effect or when it is impossible to take the drug orally.
Application
pills
Starting treatment. The usual recommended dose for adults is 200 mg 3 times a day for 8-10 days. In some cases, higher doses (4-5 tablets per day) may be used at the beginning of treatment, which should be taken for a short period and under ECG monitoring.
Maintenance therapy. The minimum effective dose should be used. Depending on the tolerability of the drug, the maintenance dose for adults can range from 1/2 tablet per day (1 tablet every 2 days) to 2 tablets per day.
Tablets are taken orally, with a small amount of water. Tablets can be taken during or after meals as a single dose or divided into 2-3 doses regularly at the same time. A missed dose should be taken as soon as possible. If it is almost time for the next dose, wait and take only the scheduled dose (DO NOT double the dose).
Solution for injection
Do not dilute the drug with isotonic sodium chloride solution, as precipitate formation is possible!
Do not mix with other drugs in the same infusion system.
Cardiodarone can only be administered in isotonic (5%) glucose solution.
Amiodarone should be administered through a central vein. If central venous access is not possible, the drug can be administered through a peripheral vein (see Precautions).
The dose is selected individually depending on the patient's condition.
IV infusion
Start of treatment (loading dose): the usual dose is 5 mg/kg body weight. The dose is administered in 250 ml of 5% glucose solution over 20 minutes to 2 hours. The dose can be repeated 2-3 times during the day. The maximum daily dose should not exceed 1200 mg.
The maintenance dose is 10-20 mg/kg daily (usually 600 to 800 mg/day, but not more than 1200 mg/day) in 500 ml of 5% glucose solution. Infusion therapy usually lasts 4-5 days.
The tablet form of the drug should be started on the 1st day of infusion therapy.
Intravenous injection
The usual dose is 5 mg/kg body weight and should be administered over 3 minutes. The next IV injection can be given no earlier than 15 minutes after the previous one, even if only part of the contents of 1 ampoule has been used. The therapeutic effect appears in the first minutes, and then gradually decreases. Thus, an infusion must be used to maintain the effect.
Contraindication
Hypersensitivity to iodine, amiodarone or any component of the drug;
- sinus bradycardia or sinoatrial heart block (heart rate 50-55 beats / min) in the absence of correction by an artificial pacemaker (pacemaker);
- sick sinus syndrome in the absence of correction by an artificial pacemaker (risk of sinus node arrest);
- high-grade conduction disturbances (AV block, bi- and trifascicular bundle of His block) in the absence of correction by an artificial pacemaker;
- vascular insufficiency;
- severe arterial hypotension;
- thyroid disease (hyperthyroidism);
- pregnancy, especially the I and II trimesters (except in urgent cases when the expected effect justifies the possible risk) and breastfeeding;
- childhood.
Combination therapy with drugs that can cause polymorphic ventricular tachycardia of the flutter/flicker type:
- class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide);
- class III antiarrhythmic drugs (sotalol, dofetilide, ibutilide);
- other drugs such as bepridil, cisapride, diphemanil, erythromycin (iv), mizolastine, moxifloxacin, spiramycin (iv), vincamine (iv);
- sultopride.
Intravenous injections are contraindicated in severe respiratory failure, decompensated cardiomyopathy, and severe heart failure.
The most common side effect of treatment with amiodarone in the form of a solution for injection is arterial hypotension. The incidence of arterial hypotension is approximately 16%. The possibility of developing arterial hypotension and collapse depends mainly on the rate of administration of the drug, not on the dose.
Local reactions: possible inflammation of the veins after intravenous infusion.
From the side of the cardiac system:
- often: usually moderate, dose-dependent bradycardia (with oral administration); severe bradycardia (with parenteral administration);
- very rarely: moderate bradycardia, conduction disturbances (sinoauricular blockade, AV blockade of varying degrees), exacerbation of an existing arrhythmia or development of a new one, which sometimes results in cardiac arrest, the onset or exacerbation of heart failure;
- isolated cases: severe bradycardia, in exceptional cases - sinus node arrest (with sinus node dysfunction, in elderly patients).
From the vascular system:
- often: arterial hypotension (severe arterial hypotension or collapse are possible in case of overdose or very rapid administration) (with parenteral use);
- very rarely: hot flashes;
- isolated cases: vasculitis.
On the part of the respiratory system:
- often: cases of diffuse interstitial or alveolar pneumopathy and obstructive bronchiolitis with pneumonia. The appearance of dyspnea on exertion or dry cough, both separately and against the background of a deterioration in the general condition (fatigue, weight loss, slight increase in body temperature), requires an X-ray examination and, if necessary, discontinuation of treatment. Such types of pneumopathy can actually develop into pulmonary fibrosis.
Early withdrawal of amiodarone (with or without concomitant glucocorticosteroid therapy) leads to a reduction in such events. Clinical symptoms usually disappear after 3-4 weeks. Radiographic and functional improvement occurs more slowly (over several months).
Several cases of exudative pleurisy have been reported, usually occurring in the setting of interstitial pneumonia.
- isolated cases: bronchospasm, particularly in patients with bronchial asthma; acute respiratory distress syndrome, rarely fatal, which sometimes occurred immediately after surgery (possibly due to interaction with high doses of oxygen).
Cases of pulmonary hemorrhage have been reported.
From the gastrointestinal tract:
- often: nausea, vomiting, taste disturbances, which usually occur at the beginning of treatment and disappear when the dose is reduced, constipation, loss of appetite.
From the hepatobiliary system:
- often: hepatomegaly, moderate increase in transaminase levels (1.5-3 times);
- rarely: hepatitis, which disappears after discontinuation of treatment; acute liver dysfunction with high serum transaminase levels and/or jaundice (sometimes fatal) - in such cases, treatment should be discontinued;
- isolated cases: non-alcoholic steatohepatitis. Therefore, regular monitoring of liver function is necessary.
From the thyroid gland:
- often: changes in thyroid hormone levels (increased T4 levels with normal or slightly decreased T3 levels), in the absence of clinical signs of dysthyroidism, which does not require discontinuation of treatment;
- rarely: hypothyroidism (weight gain, sensitivity to cold, apathy, drowsiness). A significant increase in TSH levels confirms this diagnosis. After discontinuation of treatment, gradual normalization of thyroid function is observed within 1-3 months, so drug withdrawal is not required. If necessary, treatment with amiodarone can be continued, combining it with replacement therapy with levothyroxine sodium, while the dose of levothyroxine sodium is determined depending on the TSH level.
Hyperthyroidism can be diagnosed during the use of the drug or several months after discontinuation of therapy. Its clinical symptoms are mild (slight weight loss of unknown etiology, decreased antianginal and / or antiarrhythmic efficacy of the drug). In the elderly, mental disorders or even thyrotoxicosis are possible. A decrease in TSH levels confirms this diagnosis. In this case, the use of amiodarone should be discontinued. This is usually sufficient to achieve clinical recovery after 3-4 weeks. In serious cases, which can be fatal, appropriate treatment should be carried out immediately.
If the patient's condition is of concern, then, given the variable efficacy of synthetic antithyroid drugs, immediate corticosteroid therapy (1 mg/kg body weight) for a long time (up to 3 months) is recommended.
From the nervous system:
- common: tremor or other extrapyramidal symptoms; sleep disturbances, including nightmares; sensory, motor or mixed peripheral neuropathies;
- rarely: myopathy.
Sensory, motor or mixed peripheral neuropathy and myopathy may occur within a few months of treatment, although sometimes several years. They usually resolve after discontinuation of the drug. However, recovery may be incomplete, very slow and may not occur until several months after discontinuation of treatment.
- isolated cases: cerebellar ataxia, benign intracranial hypertension, headache.
- very common: microdeposit in the corneal area of lipofuscin (a lipid complex), most often localized in the area under the pupil, but its appearance is not a contraindication to continuing therapy. Microdeposit always disappears after discontinuation of treatment. Extremely rarely, it can lead to visual impairment in the form of a colored halo when looking at an object in bright light or blurred vision;
- isolated cases: optic neuropathy (optic neuritis), accompanied by decreased visual acuity and papillary edema on the fundus. The connection with the use of amiodarone has not been established to date. However, in the presence of another obvious cause, it is recommended to discontinue treatment with amiodarone.
On the skin:
- common: photosensitivity. Patients should be warned to avoid direct exposure to sunlight (any UV radiation) during treatment;
- rarely: the appearance of grayish or bluish skin pigmentation with prolonged use of high daily doses. After discontinuation of the drug, this pigmentation slowly disappears (within 10-24 months);
- rare: erythema during radiotherapy; skin rash, exfoliative dermatitis, although the relationship between its occurrence and taking the drug has not been clearly established; hair loss.
On the part of the reproductive organs:
- isolated cases: epididymitis. However, the relationship with the use of the drug has not been established.
From the hematopoietic system:
- isolated cases: thrombocytopenia.
On the part of the immune system:
- Cases of angioedema have been reported;
- very rare: anaphylactic shock.
Change in laboratory parameters:
- isolated cases: renal failure, accompanied by a moderate increase in creatinine levels.
Special instructions
Amiodarone treatment should be carried out and supervised only by a physician who has the necessary knowledge and experience in the treatment of cardiac arrhythmias. Treatment with the parenteral form of the drug should preferably be carried out in intensive care units with constant monitoring of the function of the cardiovascular system and control of the likelihood of side effects of the drug.
In case of impaired hemodynamics (severe arterial hypotension, circulatory failure), intravenous injections are not recommended. They can be prescribed only in urgent cases when other treatment has been ineffective. The time of administration of the first dose should be at least 3 minutes. A repeated intravenous injection should be administered no earlier than 15 minutes after the previous one, even if only part of the contents of 1 ampoule has been used (due to the possibility of collapse).
If possible, the solution for injection should be administered as an intravenous infusion. Since intravenous infusion of amiodarone may be accompanied by phlebitis, it is recommended to administer the drug through a central venous catheter.
Hypotension, bradycardia and AV block may occur during infusion therapy, therefore it is necessary to carefully monitor the infusion rate and strictly follow the dosage recommendations.
The pharmacological action of amiodarone may affect:
cardiac activity
Before starting treatment, it is recommended to perform an ECG, examine thyroid function (quantitative TSH test) and determine the patient's serum potassium level.
Elderly patients may experience bradycardia.
The frequency and severity of side effects are dose-dependent, so the minimum effective maintenance dose should be prescribed.
Amiodarone can cause ECG changes, including prolongation of the QT interval (due to prolonged repolarization) and the appearance of a U wave. These changes are not associated with the cardiotoxic effects of the drug.
In the event of sinoatrial block or AV block II or III degree, or bifascial bundle branch block, treatment should be discontinued. When treating with amiodarone, ECG should be monitored regularly (once every 3 months) and immediately if new attacks of arrhythmia or signs of exacerbation of the underlying disease occur.
There have been reports of the emergence of a new type of arrhythmia or worsening of an existing arrhythmia for which treatment is being given.
pulmonary manifestations
Progressive dyspnea and nonproductive cough may be signs of pulmonary toxicity of amiodarone. Regular chest X-rays and functional respiratory tests (every 6 months) are recommended. They are mandatory if signs of pulmonary insufficiency develop.
Amiodarone may cause thyroid dysfunction, especially in patients with a history of thyroid disease (including family history). Monitoring of thyroid function is recommended for all patients before, during treatment and for several months after its discontinuation, as well as in case of suspicion of thyroid dysfunction. The presence of iodine in the composition of the drug may distort the indicators of some functional tests of the thyroid gland (radioactive iodine binding, protein-bound iodine), however, thyroid function can be assessed by determining the indicators of T 3, T 4, TSH.
Liver manifestations
During treatment with amiodarone, serum liver enzyme activity should be monitored regularly. Regular monitoring of liver function is recommended before starting treatment and at regular intervals during treatment with amiodarone.
Amiodarone can cause sensory, motor, or mixed peripheral neuropathy and myopathy.
Manifestations from the organ of vision
In case of deterioration of visual clarity or decrease in visual acuity, a complete ophthalmological examination, including examination of the fundus, should be performed immediately. Amiodarone should be discontinued in case of development of neuropathy or optic neuritis caused by the action of amiodarone.
Patients taking amiodarone should avoid direct sunlight. Given the possibility of photosensitivity during this period, it is advisable to apply sunscreen to exposed skin in the summer.
anesthesia
Before performing surgical interventions, it is necessary to inform the anesthesiologist that the patient is using amiodarone.
Long-term use of amiodarone may increase the risk of hemodynamic disturbances associated with general or local anesthesia and the occurrence of side effects, especially such as bradycardia, hypotension, decreased cardiac output, and conduction disturbances.
In addition, patients receiving amiodarone therapy may develop acute respiratory distress syndrome after surgery, so constant monitoring of the patient's condition is necessary when using oxygen therapy in the postoperative period.
laboratory tests
Amiodarone contains iodine, so it may affect the results of thyroid function tests, especially T3, T4, and TSH levels.
During treatment with amiodarone, it is necessary to regularly check the activity of liver enzymes, in particular aminotransferases.
Elderly patients
Caution should be exercised when treating elderly patients. These patients are more likely to have decreased liver and kidney function, as well as decreased cardiac function. Some patients may also have comorbidities for which they may be taking other medications. Therefore, therapy should be initiated at the lowest effective and maintenance dose.
Children: The efficacy and safety of amiodarone in children have not been established, so the drug is not used in children.
Use of amiodarone during pregnancy and breastfeeding. Animal studies have not revealed any teratogenic effects of the drug. However, to date there are insufficient clinical data to assess the probable teratogenic effects of amiodarone when used in the first trimester of pregnancy.
Given the effect of amiodarone on the thyroid gland, the use of the drug is contraindicated in the II and III trimesters of pregnancy.
Since amiodarone passes into breast milk, breastfeeding should be discontinued during the use of amiodarone.
Ability to influence the reaction rate when driving vehicles or working with other mechanisms. There have been no reports of the effect of amiodarone on the ability to drive vehicles and complex mechanisms. However, it should be remembered that sometimes the patient may experience dizziness, and this may affect the ability to drive vehicles or work with potentially dangerous mechanisms.
Interactions
Due to its long t½, amiodarone may cause interaction effects with other drugs even several months after discontinuation of its use.
The simultaneous use of Cardiodarone with drugs that may cause paroxysmal ventricular tachycardia of the flutter/flicker type is contraindicated:
- class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide);
- class III antiarrhythmic drugs (dofetilide, ibutilide, sotalol);
- bepridil, cisapride, diphemanil, erythromycin (iv), mizolastine, vincamine (iv), moxifloxacin, spiramycin (iv);
- sultoprid.
With simultaneous use with amiodarone, the risk of developing ventricular arrhythmias increases, especially paroxysmal tachycardia of the flutter/flicker type.
Combination therapy with the following drugs is not recommended:
Cyclosporine: increased levels of cyclosporine circulating in the blood plasma due to a decrease in its metabolism in the liver - risk of nephrotoxic effects.
It is recommended to measure cyclosporine serum concentrations, monitor renal function, and adjust its dose both during and after treatment with amiodarone.
Caution should be exercised during general anesthesia due to the risk of bradycardia (resistant to atropine), hypotension, conduction disturbances and decreased stroke volume.
Diltiazem injection: risk of bradycardia and AV block. If this combination is necessary, the patient should be carefully monitored and ECG should be monitored continuously.
Halofantrine, pentamidine, lumefantrine: increased risk of ventricular arrhythmias, especially paroxysmal tachycardia of the flutter/flicker type. If possible, discontinue non-antibacterial drugs that provoke paroxysmal tachycardia of the flutter/flicker type. If such a combination is necessary, preliminary monitoring of the QT interval and constant ECG monitoring should be performed.
With simultaneous use with amiodarone, the risk of developing ventricular arrhythmias increases, especially paroxysmal tachycardia of the flutter/flicker type.
It is not recommended to prescribe amiodarone simultaneously with stimulant laxatives, as they increase the risk of hypokalemia and ventricular arrhythmia.
Due to the increased risk of ventricular arrhythmias, the concomitant administration of amiodarone and stimulant laxatives is not recommended, as they increase the risk of hypokalemia.
Use caution when prescribing Cardiodarone in combination with the following drugs:
Oral anticoagulants: due to increased plasma concentrations of anticoagulants, increased anticoagulant effect and increased risk of bleeding. It is necessary to monitor blood prothrombin levels and INR more often, as well as adjust the dose of oral anticoagulants during treatment with amiodarone and after its withdrawal.
β-adrenergic blockers, except sotalol (combination contraindicated) and esmolol (combination requiring caution in use): risk of impaired myocardial contractility, automaticity and conduction function (suppression of sympathetic compensatory mechanisms). Clinical and ECG monitoring of the patient's condition is necessary.
β-adrenergic blockers used in heart failure (bisoprolol, carvedilol, metoprolol): impaired automaticity and conduction (synergism of effects) with the risk of excessive bradycardia. There is an increased risk of developing ventricular arrhythmias, in particular paroxysmal tachycardia of the flutter/flicker type. Regular clinical and ECG monitoring of the patient's condition is necessary.
Cardiac glycosides: when used simultaneously with cardiac glycosides, disturbances of automatism (in the form of significant bradycardia) and disturbances of AV conduction are possible, as well as an increase in the concentration of digoxin in the blood serum (due to a decrease in its excretion). When taking amiodarone, it is necessary to monitor the level of digoxin in the blood, ECG indicators and, if necessary, reduce the dose of digoxin (by 1/2) or cancel it.
Oral diltiazem: risk of bradycardia and AV block, especially in elderly patients. ECG monitoring and clinical observation of the patient is necessary.
Esmolol: impaired cardiac contractility, automaticity and conduction functions (compensatory mechanisms of the sympathetic nervous system are suppressed). ECG and clinical monitoring of the patient's condition are necessary.
Drugs that can cause hypokalemia:
- diuretics that promote potassium excretion (mono- or in combination);
- glucocorticoids (systemic);
- amphotericin B (in / in);
- synthetic corticotropin (tetracosactide).
An ECG and clinical monitoring of the patient's condition and laboratory examination are necessary.
Hypokalemia may cause additional prolongation of the QT interval and increase the risk of ventricular arrhythmias, including polymorphic ventricular tachycardia of the torsades de pointes/fibrillation type. If necessary, the QT interval should be monitored and possible hypokalemia should be compensated by additional potassium administration. The use of antiarrhythmic drugs is not recommended in the presence of ventricular tachycardia of the torsades de pointes/fibrillation type. If necessary, the patient can be given a temporary pacemaker and intravenous magnesium sulfate solution.
Lidocaine: risk of increased plasma lidocaine concentrations with the possibility of neurological and cardiac adverse effects due to decreased metabolism by amiodarone. Clinical and ECG monitoring of the patient is necessary, and if necessary, monitoring of plasma lidocaine concentrations or dose adjustment of lidocaine during and after amiodarone administration and after its discontinuation.
Orlistat: risk of decreased plasma concentrations of amiodarone and its active metabolite.
Clinical and, if necessary, ECG monitoring of the patient's condition is necessary.
Phenytoin (and probably fosphenytoin): increased plasma concentrations of phenytoin with signs of overdose, especially neurological (due to decreased hepatic metabolism of phenytoin). Clinical observation, monitoring of plasma phenytoin concentrations and, if necessary, dose adjustment are required.
Simvastatin: increased risk of side effects (depending on the dose), such as rhabdomyolysis (due to reduced metabolism of simvastatin in the liver). The dose of simvastatin should not exceed 20 mg / day. If at this dose it is impossible to achieve a therapeutic effect, it is necessary to use another statin that does not have the specified interaction.
Combinations to consider
Acute respiratory distress syndrome, sometimes fatal, has been reported in patients receiving intravenous amiodarone. This may be a response to high concentrations of oxygen, and caution should be exercised when using oxygen therapy in the postoperative period. The anesthesiologist should be informed of the patient's use of amiodarone prior to scheduled surgery.
There are only two reports of interactions during infusion of amiodarone in the literature. One patient experienced convulsions when amiodarone and lidocaine were administered concomitantly due to increased serum lidocaine levels. Another patient experienced renal impairment when amiodarone and cyclosporine were administered concomitantly due to decreased cyclosporine excretion (by 50%). Therefore, frequent monitoring of cyclosporine serum levels is necessary when amiodarone and cyclosporine are administered concomitantly.
There have been isolated reports of myopathy/rhabdomyolysis during concomitant treatment with amiodarone and high doses of simvastatin.
Overdose
Cases of overdose with amiodarone have been reported. Isolated cases of sinus bradycardia, heart block, ventricular tachycardia, polymorphic ventricular tachycardia of the flutter/flicker type, circulatory disorders and liver function have been reported.
Treatment is symptomatic. There is no specific antidote. Bradycardia can be treated with atropine, β-blocker agonists, glucagon, or a temporary pacemaker. Hypotension is treated with inotropic and/or vasopressor agents.
Hemodialysis is ineffective for removing amiodarone from the body.
Storage conditions
In a place protected from light at a temperature not exceeding 25 °C.
