Amiodarone

Author: Prof. Dr. med. Peter Altmeyer

All authors of this article

Last updated on: 29.10.2020

Dieser Artikel auf Deutsch

Synonym(s)

Amiodarone hydrochloride; CAS number: 1951-25-3; CAS number: 19774-82-4

Definition
This section has been translated automatically.

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.

Pharmacodynamics (Effect)
This section has been translated automatically.

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.

Undesirable effects
This section has been translated automatically.

Lung: The most severe side effect is the development of interstitial pulmonary fibrosis (Kang IS et al. 2014). In about 5% of the treated patients, fibrosing alveolitis occurs (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 manifests itself in a significantly reduced diffusion capacity of the lung (DLCO in the lung function test).

Thyroid gland: Due to the high iodine content of the drug (37 %), thyroid dysfunction is too frequent. Over- or under-functioning of the thyroid gland is found in up to 40% of long-term patients. Amiodarone suppresses the production of TSH. Therefore, thyroid function must be monitored 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: Micro deposits 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 bluish tinge to their vision. The corneal deposits should only lead to discontinuation of the drug in cases of pronounced visual impairment.

Gastrointestinal tract: About 50% of the patients show a reversible increase in liver enzymes as a sign of liver parenchyma damage. This may disappear even though the patient continues to take the drug. In very rare cases, amiodarone can lead to the appearance of acute toxic hepatitis or chronic liver damage, including liver cirrhosis.

Skin: Light-skinned people are more sensitive to light (increased risk of sunburn). Sun-exposed skin can turn greyish blue in fair-skinned people. The skin discolouration gradually disappears after weaning (Dereure O, 2001). However, they can persist for years (see below amiodarone hyperpigmentation). It is recommended to prophylactically take sun protection products which block mainly long-wave UV radiation.

NZN: Amiodarone can lead to a demyelinating polyneuropathy. Furthermore, it is not uncommon for sleep disorders to occur.

Inhibition of vitamin A absorption: Amiodarone inhibits the enzyme retinyl ester hydrolase both in the liver and the intestine. Prolonged intake therefore causes an artificial vitamin A deficiency which cannot be corrected by taking the vitamin.

Interactions
This section has been translated automatically.

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

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

Conversely, the intake of grapefruit juice via a complete inhibition of N-desethylamiodarone production can significantly increase the plasma concentration of amiodarone.

Preparations
This section has been translated automatically.

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

Note(s)
This section has been translated automatically.

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

Literature
This section has been translated automatically.

  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.

Authors

Last updated on: 29.10.2020