Philippe Camus, M.D.

Dijon, France

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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 (interstitial lung disease/ILD)

I.b

Pneumonitis (ILD), acute and/or severe (may cause ARDS)

I.c

Eosinophilic pneumonia (pulmonary infiltrates and eosinophilia)

I.d

Acute eosinophilic pneumonia (AEP)

I.e

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

I.f

Acute fibrinous organizing pneumonia (AFOP)

I.g

Pulmonary fibrosis

I.i

Subclinical pulmonary infiltrates/ILD

I.l

Lung nodule or nodules

I.m

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

I.t

A mass or masses

I.v

Relapsing or migrating pneumonitis/pneumonia (see also Id)

I.x

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

I.aa

An area or areas of consolidation

I.ab

Delayed ILD, -pneumonitis, -fibrosis

I.ap

Pulmonary infiltrates

I.au

Amiodarone pulmonary toxicity - Amiodarone lung

I.ay

Chronic pneumonitis

I.az

Unilateral interstitial lung disease

XLI - Pulmonary edema - Acute lung injury - ARDS

XLII - Pulmonary/alveolar./airway hemorrhage/bleeding

XLIII - Airway involvement

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

XLV - Pleural and/or pericardial involvement

XLVI - Pulmonary vasculopathy

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

XLIX - Systemic/Distant conditions, syndromes and reactions

L - Miscellaneous

LI - Cardiovascular involvement / toxicity

LIV - Pulmonary physiology - PFTs

LV - Imaging

LV.b

Imaging: Ground-glass opacities (GGO) / shadowing

LV.i

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

LV.j

Imaging: Wandering (migratory) pulmonary opacities

LV.n

Imaging: Intralobular septal thickening - Crazy paving

LV.s

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

LV.w

Imaging: Lung nodule or nodules

LV.x

Imaging: Waxing and waning nodules

LV.ab

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

LV.ac

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

LV.ba

Imaging: Asymmetrical, predominantly unilateral involvement

LV.bb

Imaging: Solitary pulmonary nodule

LV.bn

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

LV.bt

Imaging: A pattern consistent with pleuroparenchymal fibroelastosis

LV.bv

Imaging: A subsolid lung nodule or nodules

LV.cb

Imaging: Disseminated patchy pulmonary opacities

LVI - Distinctive patterns - 'Eye-catchers'

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

LVIII - Pathology

LVIII.a

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

LVIII.b

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

LVIII.c

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

LVIII.d

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

LVIII.e

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

LVIII.k

Path: Desquamative interstitial pneumonia (DIP-pattern)

LVIII.o

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

LVIII.q

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

LVIII.r

Path: Alveolar hemorrhage (see also IIIa)

LVIII.v

Path: NSIP-fibrotic pattern

LVIII.w

Path: Pulmonary fibrosis (UIP-pattern)

LVIII.aa

Path: Endogenous lipoid pneumonia (phospholipidosis)

LVIII.ae

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

LVIII.ag

Path: Histiocytic proliferation

LVIII.aj

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

LVIII.ak

Path: Smudged geographic necrosis

LVIII.bm

Path: Pleuritis, pleural fibrosis

LIX - Infections & related conditions