Amiodarone for abnormal heart rhythms (arrhythmias) – Antiarrhythmic Drug

Amiodarone is a potent antiarrhythmic drug that is used to treat ventricular and supraventricular tachyarrhythmias. It is a benzofuran-derived, iodine-rich compound with some structural similarity to thyroxine (T4). Amiodarone contains approximately 37% iodine by weight. Each 200-mg tablet is estimated to contain about 75 mg of organic

Amiodarone Tablets

iodide, 8-17% of which is released as free iodide. Standard maintenance therapy with 200 mg amiodarone can provide more than 100 times the daily iodine requirement. It is highly lipid-soluble and is concentrated in the adipose tissue, muscle, liver, lung, and thyroid gland.^[1]

The elimination half-life of amiodarone is highly variable, ranging from 50-100 days; total body iodine stores remain increased for up to 9 months after discontinuation of the drug. Thyroid abnormalities have been noted in up to 14-18% of patients receiving long-term amiodarone therapy. However, a meta-analysis suggested that with the lower doses of amiodarone (150-330 mg) incidence of thyroid dysfunction is 3.7%. The effects range from abnormal thyroid function test findings to overt thyroid dysfunction, which may be either amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH).^{[2, 3]} Both can develop in apparently normal thyroid glands or in glands with preexisting abnormalities.

Pathophysiology

Amiodarone causes a wide spectrum of effects on the thyroid.

• Amiodarone inhibits type 1 5′-deiodinase enzyme activity, thereby decreasing the peripheral conversion of T4 to triiodothyronine (T3) and reducing the clearance of both T4 and reverse T3 (rT3). Consequently, the serum levels of T4 and rT3 increase and the serum levels of T3 decrease by 20-25%.
• Amiodarone inhibits entry of T4 and T3 into the peripheral tissue. Serum T4 levels increase by an average of 40% above pretreatment levels after 1-4 months of treatment with amiodarone. This, in itself, does not constitute evidence of hyperthyroidism (thyrotoxicosis).
• Inhibition of type 2 5′-deiodinase enzyme activity in the pituitary due to feedback regulation is seen in the first 1-3 months and leads to an increase in thyroid-stimulating hormone (TSH) levels. This is not an indication for T4 replacement in these patients. Serum TSH levels return to normal in 2-3 months as T4 concentrations rise sufficiently to overcome the partial block in T3 production. The response of TSH to thyroid-releasing hormone (TRH) may be reduced.
• Amiodarone and its metabolites may have a direct cytotoxic effect on the thyroid follicular cells, which causes a destructive thyroiditis.
• Amiodarone and its metabolite desethylamiodarone can act as a competitive antagonist of T3 at the cardiac cellular level.

In summary, serum T4 levels rise by 20-40% during the first month of therapy and then gradually fall toward high normal. Serum T3 levels decrease by up to 30% within the first few weeks of therapy and remain slightly decreased or low normal. Serum rT3 levels increase by 20% soon afterward and remain increased. Serum thyrotropin (TSH) levels usually rise after the start of therapy but return to normal in 2-3 months.

Two forms of AIT have been described. Type 1 usually affects patients with latent or preexisting thyroid disorders and is more common in areas of low iodine intake. Type 1 is caused by iodine-induced excess thyroid hormone synthesis and release (Jod-Basedow phenomenon). Type 2 occurs in patients with a previously normal thyroid gland and is caused by a destructive thyroiditis that leads to the release of preformed thyroid hormones from the damaged thyroid follicular cells. However, mixed forms of AIT may occur in an abnormal thyroid gland, with features of destructive processes and iodine excess.

The most likely mechanisms of AIH are an enhanced susceptibility to the inhibitory effect of iodine on thyroid hormone synthesis and the inability of the thyroid gland to escape from the Wolff-Chaikoff effect after an iodine load in patients with preexisting Hashimoto thyroiditis. In addition, iodine-induced damage to the thyroid follicles may accelerate the natural trend of Hashimoto thyroiditis toward hypothyroidism. Patients without underlying thyroid abnormalities are postulated to have subtle defects in iodine organification that lead to decreased thyroid hormone synthesis, peripheral down regulation of thyroid hormone receptors, and subsequent hypothyroidism.

Epidemiology

Frequency

United States

The prevalence of AIT in the United States is 3%; the prevalence of AIH is 22%. The relative prevalence of the 2 forms of AIT is unknown.

International

Some studies indicate that the incidence varies with the dietary iodine intake in the population. AIT occurs more frequently in geographical areas with low iodine intake, whereas AIH is more frequent in iodine-replete areas. However, in a Dutch study of persons with euthyroidism living in an area with moderately sufficient iodine intake, the incidence of AIT was twice that of AIH.

Mortality/Morbidity

Although amiodarone-associated thyroid dysfunction is usually a mild clinical condition, it can be severe, life threatening, and even lethal. Fatal cases of thyroid storm and myxedema coma have been reported despite various aggressive therapies.

Race

No well-described racial differences exist.

Sex

AIH is more frequent in females, with a female-to-male ratio of 1.5:1. AIT, however, is more frequent in males, with a male-to-female ratio of 3:1.

Age

The risk of AIH is higher in elderly persons,^[4] probably because of the higher prevalence of underlying thyroid abnormality.

History

The clinical presentation of AIH is usually subtle, while that of AIT can be dramatic, with life-threatening cardiac manifestations without antecedent subclinical biochemical findings. Suspect AIT in a patient who was previously stable while receiving amiodarone but who starts to show signs of cardiac decompensation, tachyarrhythmias, or angina. However, patients may lack cardiac manifestations because of amiodarone’s intrinsic effect on the heart, and other signs of hyperthyroidism such as weight loss and fatigue may predominate. Thyrotoxicosis can occur while a patient receives amiodarone and even several months after discontinuation of treatment. Hypothyroidism is rare after the first 18 months of therapy.

• Symptoms of AIT include the following:
  • Unexplained weight loss
  • Heat intolerance or increased perspiration
  • Profound muscle weakness
  • Unexplained fatigue
  • Emotional lability
  • Frequent stools
  • Oligomenorrhea
  • Anxiety, nervousness, or palpitations
• Symptoms of AIH include the following:
  • Fatigue
  • Lethargy
  • Cold intolerance
  • Mental sluggishness
  • Weakness
  • Constipation
  • Menorrhagia
  • Dry skin
• A family history of certain conditions can also be important. Consider the following:
  • Autoimmune disease
  • Thyroid disease
  • Medication history
  • Emigration from iodine-deficient areas

Physical

The physical signs of thyrotoxicosis or hypothyroidism induced by amiodarone therapy do not differ from those observed in states of thyroid excess or deficiency attributable to other causes.

• Signs of AIT include tremor, goiter, heart failure, sinus tachycardia, and atrial fibrillation.
• The presence of proptosis or multinodular or diffuse goiter usually indicates type 1 AIT. A small, often tender, goiter occasionally develops in patients with type 2 AIT.
• The clinical manifestations of AIH are similar to those of spontaneous hypothyroidism. Patients present with vague symptoms and signs such as fatigue, lethargy, cold intolerance, mental sluggishness, and dry skin. A goiter is found in 20% of patients with hypothyroidism who live in iodine-replete areas, but most of these goiters predate the start of amiodarone treatment. Myxedema coma has also been reported in a patient receiving long-term amiodarone therapy. In patients already receiving levothyroxine replacement therapy, the dose of levothyroxine may need to be increased to offset the amiodarone-induced inhibition of the T4-to-T3 conversion.

Causes

The risk of developing hypothyroidism or thyrotoxicosis is independent of the daily or cumulative dose of amiodarone. However, some small studies show the contrary. Autoimmune thyroid disease is the principal risk factor for the development of hypothyroidism. High dietary intake and a positive family history of thyroid disease may also be predisposing factors. Females with thyroid peroxidase or thyroglobulin antibodies have a relative risk of 13.5% for the development of hypothyroidism.

In this factsheet:

• How does TAJ-Amiodarone work? What will it do for me?
• How should I use TAJ-Amiodarone?
• What form(s) does TAJ-Amiodarone come in?
• Who should NOT take TAJ-Amiodarone?
• What side effects are possible with TAJ-Amiodarone?
• Are there any other precautions or warnings for TAJ-Amiodarone?
• What other drugs could interact with TAJ-Amiodarone?

Amiodarone belongs to the family of medications known as antiarrhythmics. It is used to treat certain types of abnormal heart rhythms (arrhythmias). It works by changing how electrical impulses affect the heart muscle and by making the heart beat more regularly. The effects of this medication may be noted as early as 3 days after starting treatment, but it is usually 1 to 3 weeks before beneficial effects are seen.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. As well, some forms of this medication may not be used for all of the conditions discussed here. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

How does TAJ-Amiodarone work? What will it do for me?

Amiodarone belongs to the family of medications known as antiarrhythmics. It is used to treat certain types of abnormal heart rhythms (arrhythmias). It works by changing how electrical impulses affect the heart muscle and by making the heart beat more regularly. The effects of this medication may be noted as early as 3 days after starting treatment, but it is usually 1 to 3 weeks before beneficial effects are seen.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. As well, some forms of this medication may not be used for all of the conditions discussed here. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

How should I use TAJ-Amiodarone?

The recommended adult starting dose of amiodarone is usually from 800 mg to 1,600 mg daily for the first 1 to 3 weeks in divided doses. The dose is eventually reduced to 200 mg to 400 mg once daily as prescribed by your doctor and according to circumstances. This medication may be taken with or without meals, but should be taken in the same manner each day. Do not take grapefruit juice during amiodarone treatment because blood levels of amiodarone may increase.

The injectable form of amiodarone may be used in hospitals under specific circumstances. The recommended dose varies according individual circumstances.

Many things can affect the dose of medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.

It is important to take this medication exactly as prescribed by your doctor. If you miss a dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed or skipped dose. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

Store this medication at room temperature, protect it from light and moisture, and keep it out of the reach of children.

This medication is available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms listed here. The forms available for the specific brand you have searched are listed under “What form(s) does this medication come in?”

Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

What form(s) does TAJ-Amiodarone come in?

100 mg
Each pink, round, flat face, bevelled-edge tablet, debossed with “P” logo on one side and “100” on the other, contains amiodarone HCl 100 mg. Nonmedicinal ingredients: FD&C Red No. 40 Aluminum Lake, lactose, magnesium stearate, povidone, silicon dioxide, and sodium starch glycolate.

200 mg
Each pink, round, flat face, bevelled-edge tablet, scored on one side and debossed with “P” logo and “200” on the other, contains amiodarone HCl 200 mg. Nonmedicinal ingredients: FD&C Red No. 40 Aluminum Lake, lactose, magnesium stearate, povidone, silicon dioxide, and sodium starch glycolate.

Who should NOT take TAJ-Amiodarone?

Do not use this medication if you:

• are allergic to amiodarone, iodine, or any ingredients of this medication
• have a very low heart rate
• have certain lung problems
• have hepatitis
• have second or third degree AV block (except when used with a pacemaker)
• have thyroid disease

Do not give this medication to people in cardiogenic shock.

What side effects are possible with TAJ-Amiodarone?

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

Although most of the side effects listed below don’t happen very often, they could lead to serious problems if you do not seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

Stop taking the medication and seek immediate medical attention if any of the following occur:

• blistering or peeling skin
• chest pain
• fainting
• fast or irregular heartbeat
• signs of a severe allergic reaction, e.g.:
  • hives
  • shortness of breath
  • swelling of the lips, tongue, or throat
• signs of liver problems, e.g.:
  • abdominal pain or swelling
  • dark urine
  • fever
  • itchy skin
  • loss of appetite
  • nausea and vomiting
  • pale or clay-coloured stools
  • yellowing of skin or whites of eyes
• signs of lung problems, e.g.:
  • cough
  • coughing-up of blood
  • difficulty breathing
  • fever
  • shortness of breath
  • wheezing

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Are there any other precautions or warnings for TAJ-Amiodarone?

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Abnormal heart rhythm: Amiodarone may cause a heart rhythm disturbance called QT prolongation. It can also worsen or trigger an irregular heart beat (arrhythmia). Your doctor will monitor your heart rhythm regularly while you are taking this medication with a test called an electrocardiogram (ECG).

Blood potassium and magnesium levels: People with low levels of potassium or magnesium should have these conditions corrected before starting amiodarone, as the risk of worsening abnormal heart rhythms may be increased.

Congestive heart failure: If you have congestive heart failure, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

General: Due to the potential for serious side effects, amiodarone should only be given by physicians who are experienced in the treatment of abnormal heart rhythms.

Liver disease: Amiodarone may cause liver problems, so your doctor should monitor your liver function regularly. If you have liver disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. People with hepatitis should not take amiodarone.

Lung problems: Amiodarone can cause lung problems (pulmonary fibrosis, permanent scarring of the lungs) that, in some cases, can be fatal. If you experience any difficulty breathing, wheezing, fever, shortness of breath, cough, or coughing up of blood, accompanied by weakness and weight loss while taking amiodarone, tell your doctor immediately.

Skin: Amiodarone may make your skin more sensitive to the sun. Use sunscreen with minimum SPF and protective clothing while taking amiodarone. Some people using amiodarone for long-term treatment may develop a blue-grey discoloration of exposed skin. Report any changes in skin colour to your doctor.

Surgery: If you are scheduled for surgery, inform all doctors involved in your care that you are taking amiodarone.

Thyroid disease: Amiodarone can cause thyroid problems (both overactive and underactive). Your doctor will perform tests regularly to monitor your thyroid function prior to and during amiodarone treatment, especially if you are a senior or if you have a history of thyroid problems.

Vision problems: Amiodarone may cause vision problems that may be severe or permanent. Regular eye exams are recommended during amiodarone treatment. If you notice any vision changes or problems, contact your doctor as soon as possible.

Pregnancy: This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding: This medication passes into breast milk. If you are a breast-feeding mother and are taking amiodarone, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children: The safety and effectiveness of amiodarone for use by children have not been established.

What other drugs could interact with TAJ-Amiodarone?

There may be an interaction between amiodarone and any of the following:

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

Amiodarone for abnormal heart rhythms (arrhythmias) – Antiarrhythmic Drug – Taj Dearob Pharma | Amiodarone is a potent antiarrhythmic drug that is used to treat ventricular and supraventricular tachyarrhythmias. It is a benzofuran-derived, iodine-rich compound with some structural similarity to thyroxine (T4). Amiodarone contains approximately 37% iodine by weight. Each 200-mg tablet is estimated to contain about 75 mg of organic
Amiodarone for abnormal heart rhythms (arrhythmias) – Antiarrhythmic Drug – Taj Dearob Pharma | Amiodarone is a potent antiarrhythmic drug that is used to treat ventricular and supraventricular tachyarrhythmias. It is a benzofuran-derived, iodine-rich compound with some structural similarity to thyroxine (T4). Amiodarone contains approximately 37% iodine by weight. Each 200-mg tablet is estimated to contain about 75 mg of organic
Amiodarone for abnormal heart rhythms (arrhythmias) – Antiarrhythmic Drug – Taj Dearob Pharma | Amiodarone is a potent antiarrhythmic drug that is used to treat ventricular and supraventricular tachyarrhythmias. It is a benzofuran-derived, iodine-rich compound with some structural similarity to thyroxine (T4). Amiodarone contains approximately 37% iodine by weight. Each 200-mg tablet is estimated to contain about 75 mg of organic
Amiodarone for abnormal heart rhythms (arrhythmias) – Antiarrhythmic Drug – Taj Dearob Pharma | Amiodarone is a potent antiarrhythmic drug that is used to treat ventricular and supraventricular tachyarrhythmias. It is a benzofuran-derived, iodine-rich compound with some structural similarity to thyroxine (T4). Amiodarone contains approximately 37% iodine by weight. Each 200-mg tablet is estimated to contain about 75 mg of organic