Philippe Camus, M.D.

Dijon, France

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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 (interstitial lung disease/ILD)
I.b

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

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

Pulmonary fibrosis
I.m

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

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

XLI - Pulmonary edema - Acute lung injury - ARDS

XLI.a

Pulmonary edema, noncardiogenic (NCPE)
XLI.e

ARDS - Acute lung injury
XLI.k

Flash (fulminate) pulmonary edema

XLII - Pulmonary/alveolar./airway hemorrhage/bleeding

XLII.a

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

Hemoptysis

XLIII - Airway involvement

XLIII.a

Bronchospasm - Wheezing - Asthma
XLIII.b

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

Bronchiectasis
XLIII.w

Bronchiolitis (a clinical-imaging pattern suggestive of)
XLIII.x

Obliterative bronchiolitis (a pattern consistent with) (see also IVn, XVx)
XLIII.ab

Cough (lone)
XLIII.al

Cough variant asthma

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

XLIV.x

Opportunistic large airway infection (bacterial, fungal, viral)

XLVII - Mediastinal involvement

XLVII.g

Hemomediastinum - Mediastinal hematoma

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

XLVIII.t

CNS involvement/dysfunction/damage
XLVIII.ab

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

XLIX - Systemic/Distant conditions, syndromes and reactions

XLIX.b

Antiphospholipid antibodies w/wo the APL syndrome
XLIX.f

Anaphylaxis-Anaphylactoid reaction (can be fatal)
XLIX.i

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

Sarcoid-like granulomatosis (endo-/extrathoracic)
XLIX.p

Tumor lysis syndrome (TLS)
XLIX.u

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

Flare of preexisting vasculitis

L - Miscellaneous

L.l

Neutropenia, agranulocytosis (w/wo infection/sepsis)

LI - Cardiovascular involvement / toxicity

LI.g

Cardiomyopathy (acute, subacute, chronic)
LI.h

Coronary artery disease (acute) - Myocardial ischemia/infarction

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

LVII.a

BAL: An excess proportion of lymphocytes

LVIII - Pathology

LVIII.d

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

Path: Pulmonary fibrosis (UIP-pattern)

LIX - Infections & related conditions

LIX.a

Respiratory tract infection incl. pneumonia
LIX.b

Opportunistic pulmonary/systemic infections
LIX.e

Pneumocystis jiroveci pneumonia
LIX.g

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

Fungal airway infection
LIX.q

Viral pneumonia
LIX.v

Hypogammaglobulinemia - Antibody deficiency

LXII - Rechallenge data

LXII.c

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