Presentation
In an effort to shed light on this syndrome, we present a stereotypical case study in amiodarone-induced pulmonary toxicity, as a prelude to a review of theorized pathophysiology, epidemiology, clinical presentation, diagnosis, therapeutics, monitoring [ncbi.nlm.nih.gov]
Entire Body System
- Fatigue
You may feel fatigued, lethargic, have poor exercise tolerance, and may experience dizziness and fainting. [a-fib.com]
Neurologic Common : Malaise and fatigue, tremor/abnormal involuntary movements, lack of coordination, abnormal gait/ataxia, dizziness, paresthesias, decreased libido, insomnia, headache, sleep disturbances. Ophthalmic Common : Visual disturbances. [rxlist.com]
Chronic toxicity (eg, chronic interstitial pneumonitis, organising pneumonia) is more common and presents gradually with symptoms including non-productive cough, dyspnoea, fever, pleuritic chest pain, fatigue and/or weight loss. [medsafe.govt.nz]
Tremors; lack of coordination or difficulty walking; dizziness, weakness or fatigue; trouble sleeping or sleep disturbances; headache; sexual disturbances; weight loss; abnormal taste or smell; vision problems such as blurred vision, halos around objects [my.clevelandclinic.org]
Symptoms of simvastatin liver injury include: Unusual fatigue Loss of appetite Right upper abdominal discomfort Dark urine Yellowing of the skin or whites of the eyes Simvastatin + Amiodarone Memory Loss Side Effects Also in the February 2012 update, [rotlaw.com]
- Intravenous Administration
In clinical studies of 2 to 7 days, clearance of amiodarone after intravenous administration in patients with VT and VF ranged between 220 and 440 mL/h/kg. [globalrph.com]
Administration and dosage (see Table 2) Amiodarone can be given orally or intravenously. Intravenous administration is only appropriate in hospital with continuous ECG monitoring. [nps.org.au]
Two studies have examined the value of prophylactic intravenous amiodarone administration after cardiac surgery. [anesthesiology.pubs.asahq.org]
Amiodarone is widely distributed in the body after intravenous administration, and a three-compartment model best explains its distribution kinetics ( [17] ). [onlinejacc.org]
- Myxedema
Myxedema coma secondary to amiodarone use has been rarely reported in the literature. [ncbi.nlm.nih.gov]
Mazonson PD, Williams ML, Cantley LK, Dalldorf FG, Utiger RD, Foster JR "Myxedema coma during long-term amiodarone therapy." Am J Med 77 (1984): 751-4 147. [web.archive.org]
Gastrointestinal
- Nausea
Nausea, vomiting, constipation, loss of appetite, shaking, or tiredness may occur. If any of these effects persist or worsen, tell your doctor promptly. [webmd.com]
SIDE EFFECTS Adverse reactions include fever, bradycardia, CHF, cardiac arrest, hypotension, ventricular tachycardia, nausea, and abnormal liver function. [jointemsprotocols.com]
If you experience any of the following symptoms, call your doctor immediately: nausea, vomiting, dark colored urine, excessive tiredness, yellowing of the skin or eyes, itching, or pain in the upper right part of the stomach. [medlineplus.gov]
Common side effects include: nausea, vomiting, and loss of appetite. What is amiodarone? Amiodarone affects the rhythm of your heartbeats. [drugs.com]
Possible symptoms of an overdose with this medication may include: Nausea Vomiting Constipation Loss of appetite Heart rhythm problems A slow heart rate (bradycardia) Low blood pressure (hypotension) Liver damage Jaundice (yellowing of the skin and whites [heart.emedtv.com]
- Abdominal Pain
Common : Constipation, anorexia, abdominal pain. Dermatologic Common : Solar dermatitis/photosensitivity. [rxlist.com]
Tell your doctor right away if you notice any symptoms of lung or liver problems such as cough, shortness of breath, chest pain, coughing up blood, persistent nausea/vomiting, dark urine, severe stomach/abdominal pain, or yellowing eyes/skin. [webmd.com]
Nausea, vomiting, constipation, loss of appetite, abdominal pain (about 25 percent of patients). Take amiodarone with meals. [my.clevelandclinic.org]
Your pharmacist may be able to advise you on managing side effects. abdominal pain bad taste constipation diarrhea difficulty sleeping dizziness or lightheadedness nausea sensitivity of skin to sunlight tremor vomiting Although most of the side effects [medbroadcast.com]
Jaw & Teeth
- Bleeding Gums
gums, cuts that don’t stop bleeding) 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 skin rash slow heartbeat [medbroadcast.com]
Skin
- Skin Rash
rash occur Monitor hepatic enzymes regularly in patients receiving relatively high maintenance doses; asymptomatic elevations of hepatic enzyme levels seen frequently, but therapy can cause life-threatening hepatic injury; histology has resembled that [reference.medscape.com]
Skin rash, discoloration or photo sensitivity (skin can become sensitive to sunlight). People taking amiodarone should protect themselves from the sun by wearing protective clothing and using a wide spectrum sun block. [gosh.nhs.uk]
Contact your doctor immediately if, after taking amiodarone, you experience any new symptoms such as: coughing, wheezing, shortness of breath, visual changes, skin rash, pain, tingling or weakness in the arms or legs, fever, rapid heart beat, fatigue, [a-fib.com]
Side effects that you should report to your doctor or health care professional as soon as possible: allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue blue-gray coloring of the skin blurred vision, seeing blue green [my.clevelandclinic.org]
- Alopecia
Uncommon : Blue skin discoloration, rash, spontaneous ecchymosis, alopecia, hypotension, and cardiac conduction abnormalities. Postmarketing Experience The following adverse reactions have been identified during post-approval use of CORDARONE. [rxlist.com]
Side effects Amiodarone can cause the following side effects: nausea, vomiting, taste changes, vision disturbances, photosensitivity ( increased sensitivity to sunlight ), alopecia ( hair loss ), thyroid gland disorders ( because Amiodaron contains iodine [pharmacybook.net]
Rarely, cases of toxic epidermal necrolysis, exfoliative dermatitis, reversible alopecia, bullous dermatosis, linear IgA disease, cutaneous vasculitis, and pustular psoriasis have been reported. [web.archive.org]
[…] field defect, blurred vision [ Ref ] Dermatologic Very common (10% or more): Photosensitivity (up to 10%) Common (1% to 10%): Slate-gray or bluish pigmentations of light-exposed skin Very rare (less than 0.01%): Erythema, rash, exfoliative dermatitis, alopecia [drugs.com]
- Dermatitis
Dermatologic Common : Solar dermatitis/photosensitivity. [rxlist.com]
Visual field defect, blurred vision [ Ref ] Dermatologic Very common (10% or more): Photosensitivity (up to 10%) Common (1% to 10%): Slate-gray or bluish pigmentations of light-exposed skin Very rare (less than 0.01%): Erythema, rash, exfoliative dermatitis [drugs.com]
Exfoliative dermatitis, toxic epidermal necrolysis, skin cancer, and pruritus have been reported in postmarketing experience. [web.archive.org]
- Eczema
Skin and Subcutaneous Tissue Disorders : urticaria, toxic epidermal necrolysis (sometimes fatal), erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, bullous dermatitis, drug rash with eosinophilia and systemic symptoms (DRESS), eczema [rxlist.com]
Stevens-Johnson syndrome, spontaneous ecchymosis, pustular psoriasis enhanced Postmarketing reports : Toxic epidermal necrolysis, erythema multiforme, skin cancer, pruritus, bullous dermatitis, drug rash with eosinophilia and systemic symptoms (DRESS), eczema [drugs.com]
Additional postmarketing reports have included urticaria and eczema. [ Ref ] A retrospective study of 44 patients found by univariate analysis that patients who experienced dermatologic side effects were younger than patients who did not (mean age 48 [web.archive.org]
- Pruritus
[…] and Subcutaneous Tissue Disorders : urticaria, toxic epidermal necrolysis (sometimes fatal), erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, bullous dermatitis, drug rash with eosinophilia and systemic symptoms (DRESS), eczema, pruritus [rxlist.com]
[…] dermatitis, alopecia, sweating Frequency not reported : Granuloma, angioedema, urticaria, Stevens-Johnson syndrome, spontaneous ecchymosis, pustular psoriasis enhanced Postmarketing reports : Toxic epidermal necrolysis, erythema multiforme, skin cancer, pruritus [drugs.com]
Exfoliative dermatitis, toxic epidermal necrolysis, skin cancer, and pruritus have been reported in postmarketing experience. [web.archive.org]
Urogenital
- Anuria
The broken-down muscle mass can cause other problems throughout the body such as: Electrolytic disturbances; Nausea; Vomiting; Confusion; Coma; Cardiac arrhythmia; Dark urine; Oligura or Anuria (decreased or non-existent urine production, respectively [rotlaw.com]
Neurologic
- Peripheral Neuropathy
Peripheral neuropathy during longterm high-dose amiodarone therapy. Abstract Three patients developed peripheral neuropathy after taking amiodarone for more than 18 months. [doi.org]
Three patients developed peripheral neuropathy after taking amiodarone for more than 18 months. [ncbi.nlm.nih.gov]
(reevaluate if occurs), photosensitivity, skin pigmentation, thyroid disorders, malaise, peripheral neuropathy, constipation, anorexia, blood dyscrasias, pancreatitis; peripheral vein phlebitis (w. concentrated solutions; see full labeling). [empr.com]
Neuropathy [see WARNINGS AND PRECAUTIONS ] Photosensitivity and Skin Discoloration [see WARNINGS AND PRECAUTIONS ] Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the [rxlist.com]
[…] alcoholic hepatitis or cirrhosis; obtain baseline and periodic liver transaminases; if transaminases exceed three times normal, or doubles in a patient with an elevated baseline, discontinue or reduce dose, obtain follow-up tests and treat appropriately Peripheral [reference.medscape.com]
- Headache
Neurologic Common : Malaise and fatigue, tremor/abnormal involuntary movements, lack of coordination, abnormal gait/ataxia, dizziness, paresthesias, decreased libido, insomnia, headache, sleep disturbances. Ophthalmic Common : Visual disturbances. [rxlist.com]
Tremors; lack of coordination or difficulty walking; dizziness, weakness or fatigue; trouble sleeping or sleep disturbances; headache; sexual disturbances; weight loss; abnormal taste or smell; vision problems such as blurred vision, halos around objects [my.clevelandclinic.org]
Tell your doctor if any of these symptoms are severe or do not go away: constipation loss of appetite headache decreased sex drive difficulty falling asleep or staying asleep flushing changes in ability to taste and smell changes in amount of saliva Some [medlineplus.gov]
[…] pain, coughing up blood, breathing problems that get worse; a new or a worsening irregular heartbeat pattern (fast, slow, or pounding heartbeats); a light-headed feeling, like you might pass out; blurred vision, seeing halos around lights, vision loss, headache [uofmhealth.org]
- Papilledema
An amiodarone-associated neuropathy was suspected, and amiodarone was discontinued with the approval of the cardiologist, with complete regression of the papilledema and a stabilization of visual symptoms. [ncbi.nlm.nih.gov]
[…] respiratory distress syndrome [ Ref ] Ocular Very common (10% or more): Corneal microdeposits (up to 90% or more) Common (1% to 10%): Visual disturbance Very rare (less than 0.01%): Optic neuropathy/ neuritis Frequency not reported : Permanent blindness, papilledema [drugs.com]
[…] professional: Ocular side effects have been reported the most frequently and have included corneal microdeposits (up to 98%) which only rarely caused visual halos or blurred vision, corneal opacities, lenticular changes, loss of eyelashes or eyebrows, papilledema [web.archive.org]
Workup
Rhythm
- Torsades De Pointes
Drug-induced prolongation of the corrected QT interval (QTc) may lead to serious and potentially life-threatening ventricular tachyarrhythmia, such as torsades de pointes (Tdp), which is worthy of clinical attention. [ncbi.nlm.nih.gov]
Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs. JAMA. 1993;270:2590-7. Medline 5. Kukla P, Slowiak-Lewinska T. Amiodarone-induced torsade de pointes. Five case report. Kardiol Pol. 2004;60:365-70. [revespcardiol.org]
A review with special reference to torsade de pointes tachycardia. Ann Intern Med 121: 529-535. [omicsonline.org]
Treatment
ACUTE TREATMENT Intravenously administered amiodarone is effective for the emergency treatment of ventricular tachyarrhythmias. [aafp.org]
While amiodarone is not approved for AF by the FDA, it is a commonly prescribed off-label treatment due to the lack of equally effective treatment alternatives. [en.wikipedia.org]
No significant interaction between treatment assignment and discharge survival occurred with the initiating OHCA rhythm (asystole, pulseless electric activity, or VF/VT). [ncbi.nlm.nih.gov]
Prognosis
Amiodarone induced TdP has favorable prognosis if recognized and treated promptly, and these patients should not receive amiodarone by any route in future. Copyright © 2017 Cardiological Society of India. Published by Elsevier B.V. [ncbi.nlm.nih.gov]
Nuclear medicine Gallium 67 scan: sensitive but nonspecific Treatment and prognosis Cessation of amiodarone and treatment with steroids arrests and often results in resolution of imaging findings over time 3. [radiopaedia.org]
Early recognition of toxicity and withdrawal of amiodarone is associated with a good prognosis in the majority of patients. [medsafe.govt.nz]
Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients. Am Rev Respir Dis 1990; 142:523-528. Pagina 153 - MC, et al. Ventilator-associated pneumonia caused by potentially drug-resistant bacteria. [books.google.ro]
Prognosis is favorable, with a low mortality rate, except for patients who develop respiratory distress, whose mortality approaches 50 % (3) Treatment is based on drug discontinuation and administration of corticosteroids, which should be kept for several [escardio.org]
Etiology
Of the 25 published cases of amiodarone induced acute hepatotoxicity available for review, only 10 provide evidence to conclusively implicate parenteral amiodarone as the etiology. [ncbi.nlm.nih.gov]
Indications: Ventricular fibrillation/pulseless ventricular tachycardia Ventricular tachycardia without overt signs of shock (SBP > 90) Wide complex tachycardia of unknown etiology Pediatric ventricular fibrillation/pulseless ventricular tachycardia Contraindications [orangecountyfl.net]
Major lab tests available aiming at topographic and etiologic diagnosis to be used in the preoperative period when there are questions about neuromuscular involvement are serum CK levels, electroneuromyography and muscle biopsy with histochemical study [scielo.br]
[…] to cardiopulmonary bypass. [ 57 ] However, studies linking postoperative ARDS to preoperative oral amiodarone and procedures not involving cardiopulmonary bypass, such as AICD placement under general anesthesia, [ 52,53,57 ] suggest a multifactorial etiology [anesthesiology.pubs.asahq.org]
Epidemiology
In an effort to shed light on this syndrome, we present a stereotypical case study in amiodarone-induced pulmonary toxicity, as a prelude to a review of theorized pathophysiology, epidemiology, clinical presentation, diagnosis, therapeutics, monitoring [ncbi.nlm.nih.gov]
He has since completed further training in emergency medicine, clinical toxicology, clinical epidemiology and health professional education. [lifeinthefastlane.com]
[…] type 2 AIT shows involuted follicles filled with desquamated vacuolated epithelial cells, scattered inflammatory infiltrate composed of foamy macrophages and lymphocytes, and fibrosis ( Proc (Bayl Univ Med Cent) 2008;21:382, Pathol Int 2008;58:55 ) Epidemiology [pathologyoutlines.com]
The epidemiology of IFIs is changing, although Candida albicans remains the most important fungal agent. [aac.asm.org]
Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication: a consensus statement from the International Liaison Committee on Resuscitation (American Heart Association, Australian and New Zealand Council on Resuscitation [nejm.org]
Pathophysiology
In an effort to shed light on this syndrome, we present a stereotypical case study in amiodarone-induced pulmonary toxicity, as a prelude to a review of theorized pathophysiology, epidemiology, clinical presentation, diagnosis, therapeutics, monitoring [ncbi.nlm.nih.gov]
[…] test may be helpful Monitoring amiodarone therapy, especially when amiodarone is coadministered with other drugs that may interact Evaluation of possible amiodarone toxicity Assessment of patient compliance Clinical Information Discusses physiology, pathophysiology [mayomedicallaboratories.com]
Int 2008;58:55 ) Epidemiology More frequent in males than in females (3:1) Occurs in 3% of patients treated with amiodarone in North America, increasing to 10% in countries with low iodine dietary intake ( NCBI - Amiodarone Induced Thyrotoxicosis ) Pathophysiology [pathologyoutlines.com]
Meurisse M, Gollogly L, Degauque C et al - Iatrogenic thyrotoxicosis: causal circumstances, pathophysiology, and principles of treatment-review of the literature. World J Surg, 2000;24:1377-1385. [ Links ] 27. [scielo.br]
Prevention
The drug prevents the recurrence of life-threatening ventricular arrhythmias and produces a modest reduction of sudden deaths in high-risk patients. [ncbi.nlm.nih.gov]
However, amiodarone can improve cardiac function and relieve symptoms by prevention of AF recurrence [22]. [fi.health-root.com]