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The Drug-Induced Respiratory Disease Website and App

Rituximab

When the drug is used in combination with chemotherapy drugs (R-X regimens) which can also cause respiratory problems, the respective role of each drug in causing the reaction can be difficult to evaluate (PMID 15857843), even though authors may specifically attribute causality of the AE to rituximab. When used as a solo agent for instance to treat connective tissue disease, rituximab can cause lung reactions on its own. Rituximab also exposes to the risk of pneumocystis pneumonia, which can be prevented (PMID 22157468, 23258406). Rituximab may induce hypogammaglobulinemia, which may result in infection, airway inflammation, bronchiolitis and bronchiectasis

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.d

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

Pulmonary fibrosis
I.l

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

Abnormal lung function/pulmonary physiology (PFTs) without necessarily imaging or clinical evidence

II - Pulmonary edema - Acute lung injury - ARDS

II.a

Pulmonary edema, noncardiogenic (NCPE)
II.b

ARDS - Acute lung injury
II.i

Flash (fulminate) pulmonary edema

III - Pulmonary/alveolar/airway hemorrhage/bleeding

III.a

Alveolar hemorrhage (AH), diffuse AH (DAH)
III.c

Hemoptysis

IV - Airway involvement

IV.a

Bronchospasm - Wheezing - Asthma
IV.c

Obliterative bronchiolitis (a pattern consistent with) (see also IVn, XVx)
IV.d

Cough (lone)
IV.f

Severe or catastrophic bronchospasm or asthma attack (can be fatal)
IV.j

Bronchiolitis (a clinical-imaging pattern suggestive of)
IV.k

Bronchiectasis
IV.ak

Cough variant asthma

VII - Mediastinal involvement

VII.g

Hemomediastinum - Mediastinal hematoma

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

VIII.x

Opportunistic large airway infection (bacterial, fungal, viral)

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

IX.t

CNS involvement/dysfunction/damage
IX.ab

Guillain-Barré (or GB-like) syndrome (w/wo ARF)

X - Systemic/Distant conditions, syndromes and reactions

X.b

Antiphospholipid antibodies w/wo the APL syndrome
X.f

Anaphylaxis-Anaphylactoid reaction (can be fatal)
X.g

Hypersensitivity reaction (may manifest with fever and/or skin, throat or airway involvement)
X.k

Sarcoid-like granulomatosis (endo-/extrathoracic)
X.n

Tumor lysis syndrome (TLS)
X.s

Vasculitis, pulmonary (w/wo AH), extrapulmonary, systemic: ANCA-positive
X.ao

Flare of preexisting vasculitis

XI - Miscellaneous

XI.n

Neutropenia, agranulocytosis (w/wo infection/sepsis)

XII - Cardiovascular involvement / toxicity

XII.f

Cardiomyopathy (acute, subacute, chronic)
XII.g

Coronary artery disease (acute) - Myocardial ischemia/infarction

XV - Pathology

XV.c

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

Path: Pulmonary fibrosis (UIP-pattern)

XVII - Infections & related conditions

XVII.a

Respiratory tract infection incl. pneumonia
XVII.b

Opportunistic pulmonary/systemic infections
XVII.e

Pneumocystis jiroveci pneumonia
XVII.g

Tuberculosis (pulmonary, pulmonary, extrapulmonary or disseminated). Reactivation or de novo
XVII.m

Fungal airway infection
XVII.q

Viral pneumonia
XVII.w

Hypogammaglobulinemia - Antibody deficiency

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

XIX.a

BAL: An excess proportion of lymphocytes

XXI - Rechallenge data

XXI.c

Tolerance can be induced successfully starting with minute dosage of the drug