Amiodarone

Drug (molecular formula: C25H29I2NO3), which is used as a second-choice remedy against tachycardic arrhythmias (especially against ventricular and supraventricular arrhythmias). Amiodarone is a benzofuran derivative (phthalide derivative) and has structural similarities with thyroxine and procainamide. In commercially available drugs the active ingredient is present as amiodarone hydrochloride.

Amiodarone is distinctly lipophilic. This lipophilicity causes the extraordinarily high distribution volume and is also responsible for the long half-life of 30 to well over 100 days. The elimination takes place to > 95% in the liver. The smaller remainder is excreted renally.

Amiodarone is a calcium anatgonist with a complex, as yet largely unknown mode of action. Due to its property of prolonging the refractory period and the action potential of the heart muscle tissue, it is classified as a class III antiarrhythmic agent according to Vaughan Williams with strong inhibition of the potassium channels. Amiodarone also has a moderately strong inhibitory effect on alpha, beta (Class II) and muscarinic receptors and has a blocking effect on both fast and moderate sodium (Class IA and IB) and calcium channels (Class IV).

Amiodarone also acts as a functional inhibitor of acid sphingomyelinase (FIASMA) and dilates coronary vessels, improving the oxygen supply to the heart.

Lung: The most severe side effect is the development of interstitial pulmonary fibrosis (Kang IS et al. 2014). Approximately 5% of treated patients develop fibrosing alveolitis (detected by CT). This side effect can be observed after only a few months of treatment. If the fibrosis in the preliminary stage of pneumonitis is detected in time, it is completely reversible. This is manifested by a markedly reduced diffusion capacity of the lungs (DLCO in the pulmonary function test).

Thyroid: Because of the high iodine content of the drug (37%), thyroid dysfunction is common. Hyperthyroidism or hypothyroidism is found in up to 40% of long-term treatment subjects. Amiodarone suppresses TSH production; in this respect, monitoring of thyroid function is necessary every six months (TSH measurement). The development of amiodarone-induced thyroiditis is also possible. The most feared side effect is amiodarone-induced thyrotoxicosis, which can be lethal.

Eye: Microdeposits in the cornea of the eye are found in more than 90% of patients taking the drug >0.5 years (cornea verticillata). 1 to 10% of patients report a slight blue tint in vision. Corneal deposits should lead to discontinuation of the drug only in cases of marked visual impairment.

Gastrointestinal: Approximately 50% of patients show reversible elevation of liver enzymes as a sign of hepatic parenchymal damage. This may also be reversible with continued use of the drug. In very rare cases, amiodarone can lead to the picture of acute toxic hepatitis or chronic liver damage, including cirrhosis.

Skin: Increased photosensitivity is observed in fair-skinned individuals (increased risk of sunburn). Sun-exposed skin may turn grayish-bluish in fair-skinned people. The skin discolorations gradually disappear after discontinuation (Dereure O, 2001); however, they may persist for years (see amiodarone hyperpigmentation below). The prophylactic use of photoprotective preparations that block long-wave UV radiation is recommended.

NZN: Amiodarone can lead to demyelinating polyneuropathy. Furthermore, sleep disturbances are not uncommon.

Inhibition of vitamin A uptake: Amiodarone inhibits the enzyme retinyl ester hydrolase in both the liver and intestine. Prolonged ingestion therefore produces an artificial vitamin A deficiency that cannot be corrected even by supplementation of the vitamin.

Amiodarone is a substrate of CYP3A4 and CYP2C8. This creates a high potential for interactions with drugs that are also metabolized by cytochrome P450 enzymes.

Amiodarone can thus enhance the effects of other drugs in the long term. For example, saturation with amiodarone via cytochrome interaction leads to a doubling of plasma levels of the beta-blocker metoprolol. Similarly, the effect of coumarin can be enhanced by amiodarone (Mo Y et al 2018).

Conversely, grapefruit juice ingestion can significantly increase plasma concentrations of amiodarone via complete inhibition of N-desethylamiodarone production.

Amiodarone 150mg i.v. Carino, solution for injection

Amiodarone 200 - 1 A Pharma®, tablets

Amiodarone 200 Hayman

Amiodarone 200 Heumann Heunet Tablets

Amiodarone AL 200

Amiodarone Aurobindo 200 mg tablets

Amiodarone CT 200 mg Tablets

Amiodaron-ratiopharm® 100 mg tablets

Amiodaron-ratiopharm® 150 mg/3 ml injection solution

Amiodaron-ratiopharm® 200 mg tablets

Amiodarone Sandoz® 200mg tablets

Amiodarone STADA® 200 mg tablets

AmioHEXAL® 200, 200 mg tablets

Cordarex®, 200 mg tablets

The use of amiodarone must be monitored regularly because of the wide spectrum of ADRs.

1. Dereure O (2001) Drug-induced skin pigmentation. Epidemiology, diagnosis and treatment. At J Clin Dermatol 2: 253-262
2. Dissemond J et al (2003) Hyperpigmentation of the face. dermatologist 54: 994-998
3. Drosner M, Worret WI, Marquart KH (1990) Amiodarone hyperpigmentation. Nude Dermatol 16: 67-69
4. Kang IS et al (2014) The diagnostic utility of chest computed tomography scoring for the assessment ofamiodarone-induced
   pulmonary toxicity. Korean J Intern Med 29:746-753.
5. Kudenchuk P J et al (1999) Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation. N Engl J Med. 341: 871-878.
6. Mo Y et al (2018) Evaluation of Potential Drug-Drug Interactions With Direct Oral Anticoagulants ina
   Large Urban Hospital. J Pharm Pract 1:897190018788264.