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The Drug-Induced Respiratory Disease Website and App

Amiodarone

The innumerable possible adverse effects must be checked in every patient on amiodarone (PMID 28643175). Preventative guidelines for monitoring must be adhered to (PMID 28643175). The most typical pattern of involvement is referred to as 'Amiodarone Pulmonary Toxicity' (APT) (PMID: 15062598, 23835168). Reviews at 15062598, 18460037, 22529166, 23835168. Ruling out left heart failure and its impact of PFT is important (PMID 23326457, 2337106). Imaging at PMID 11332563. Wide spectrum of respiratory manifestations can be seen. Occasionally severe or fatal. Adverse pulmonary effects can develop acutely over a few days (PMID 22315750) or up to a decade into treatment. Peak onset is 6-12 months and is somewhat dose-related. Patchy opacities in the context of malaise, cough, moderate fever and pleuritic chest pain is suggestive. Can produce an ARDS picture, especially in the postoperative setting. High attenuation numbers (>70 HU) of liver and thyroid on unenhanced CT are suggestive. Drug discontinuance, though necessary, often does not suffice and steroids are indicated. Management of underlying arrhythmia essential. Prolonged corticosteroid therapy often indicated. Most patients exhibit late cicatricial opacities. In a few, pulmonary fibrosis follows. Pulmonary toxicity can develop after low-dose amiodarone (PMID 9283542). Guidelines for monitoring available at PMID 10871966, 14749697, 19399307, 21507859, 21870892, 23640245. Studies indicate that these are suboptimally implemented. Relative risk of AE for each organ system vs. placebo available at PIMD 31871983

Frequency - Incidence

Incidence of respiratory adverse event(s) due to the specific drug as assessed by number of reported/published cases in the literature. Red digits in stars indicate: 0 = Very rare, questionable signal · 1 = < 10 cases · 2 = 10-50 cases · 3 = 50–100 cases · 4 = 100-200 cases · 5 = >200 cases

Evidence level/grade

Evidence level for respiratory adverse event(s) due to the specific drug as estimated using Hill’s (1965), Naranjo’s (1981), and Bégaud’s (1985) criteria applied to published cases. Blue digits in stars indicate: 0 = Questionable · 1 = Low · 2 = Moderate · 3 = Robust · 4 = Definite · 5 = Unquestionable, pathognomonic

I - Interstitial/parenchymal lung disease

I.a

Pneumonitis (ILD), acute and/or severe (may produce the ARDS pattern)

I.b

Pneumonitis (interstitial lung disease/ILD)

I.c

Eosinophilic pneumonia (pulmonary infiltrates and eosinophilia)

I.d

Organizing pneumonia pattern (an area or areas of consolidation on imaging)

I.e

Acute eosinophilic pneumonia (AEP)

I.f

Acute fibrinous organizing pneumonia (AFOP)

I.g

Pulmonary fibrosis

I.h

Subclinical pulmonary infiltrates/ILD

I.k

Lung nodule or nodules

I.l

Diffuse alveolar damage (DAD) (see alsoo under IIb and XVf)

I.s

A mass or masses

I.u

Relapsing or migrating pneumonitis/pneumonia (see also Id)

I.w

Rapidly progressive ILD/pulmonary fibrosis (Hamman-Rich syndrome)

I.z

An area or areas of consolidation

I.aa

Delayed ILD, -pneumonitis, -fibrosis

I.ao

Pulmonary infiltrates

I.at

Amiodarone pulmonary toxicity - Amiodarone lung

I.ax

Chronic pneumonitis

I.ay

Unilateral interstitial lung disease

II - Pulmonary edema - Acute lung injury - ARDS

III - Pulmonary/alveolar/airway hemorrhage/bleeding

IV - Airway involvement

V - Pleural and/or pericardial involvement

VI - Pulmonary vasculopathy

VIII - Central-large-upper airway (incl. pharyngeal-nasal) involvement

IX - Neuromuscular / CNS involvement - Disordered breathing (during sleep)

X - Systemic/Distant conditions, syndromes and reactions

XI - Miscellaneous

XII - Cardiovascular involvement / toxicity

XV - Pathology

XV.a

Path: NSIP-cellular pattern (see also Ia, Ib)

XV.b

Path: Eosinophilic pneumonia (subacute or acute) (see also Ic)

XV.c

Path: Organizing pneumonia (OP/BOOP) pattern (see also Id)

XV.d

Path: Acute fibrinous organizing pneumonia (AFOP-pattern) (see also pattern If)

XV.f

Path: Diffuse alveolar damage (DAD-pattern) (see also IL)

XV.g

Path: Alveolar hemorrhage (see also IIIa)

XV.h

Path: NSIP-fibrotic pattern

XV.i

Path: Pneumocyte atypia (reactive epithelial cells) (a.k.a. the "Napoleon Hat" sign)

XV.j

Path: Pulmonary fibrosis (UIP-pattern)

XV.k

Path: Desquamative interstitial pneumonia (DIP-pattern)

XV.m

Path: Lymphoid hyperplasia (including nodular- or a lymphocytic interstitial pneumonia pattern)

XV.o

Path: Endogenous lipoid pneumonia (phospholipidosis)

XV.r

Path: Smudged geographic necrosis

XV.ao

Path: Pleuritis, pleural fibrosis

XV.bt

Path: Histiocytic proliferation

XV.co

Path: Foamy inclusions in alveolar macrophages and/or in other lung cells

XV.dc

Path: Acute eosinophilic pneumonia pattern (see also under XVIb)

XVI - Imaging

XVI.b

Imaging: Ground-glass opacities (GGO) / shadowing

XVI.i

Imaging: An area or areas of involvement with a recognizable anatomic distribution

XVI.j

Imaging: Wandering (migratory) pulmonary opacities

XVI.n

Imaging: Intralobular septal thickening - Crazy paving

XVI.s

Imaging: An area or areas of involvement with high attenuation numbers or metallic density

XVI.w

Imaging: Lung nodule or nodules

XVI.aa

Imaging: Nodules, mass or masses with a central area of low attenuation (see also under XVIaa)

XVI.ab

Imaging: Cavitating/cavitary lung nodule, mass or nodules (see also Iq, XIs, XIIi, XVIaa and XVIIp)

XVI.ay

Imaging: Asymmetrical, predominantly unilateral involvement

XVI.az

Imaging: Solitary pulmonary nodule

XVI.bj

Imaging: Atelectasis (a combination of increased density and volume loss. Typically lobar)

XVI.bq

Imaging: A pattern consistent with pleuroparenchymal fibroelastosis

XVI.bt

Imaging: A subsolid lung nodule or nodules

XVI.bx

Imaging: Waxing and waning nodules

XVI.ca

Imaging: Disseminated patchy pulmonary opacities

XVII - Infections & related conditions

XVIII - Distinctive patterns - 'Eye-catchers'

XIX - Cytological, biochemical features of/in BAL, pleural fluid or FNA

XXVIII - Pulmonary physiology - PFTs