Causality assessment · Causality: well established

Methimazole and Agranulocytosis: is the FAERS signal real?

n=259 co-reports · PRR 38.2 · ROR 39.4

Methimazole side-effect profile All assessments See in the full list

A written Bradford Hill assessment of one drug–event pair. The grade is a judgement about the signal, not a statement that this drug causes this event in any one person; FAERS counts are reports, not rates.

Causality: well established

Methimazole ↔ Agranulocytosis

n=259 co-reports · PRR 38.2 · ROR 39.4

The antithyroid drugs methimazole and propylthiouracil are classic causes of drug-induced agranulocytosis, a sudden loss of neutrophil granulocytes that leaves patients vulnerable to severe infection. It is the single most feared haematologic complication of treating hyperthyroidism, and it typically appears within the first weeks to months of therapy. Because it can be sudden, patients are counselled to seek urgent care for fever or sore throat — a classic “report immediately” symptom drill taught for this drug class. The reaction is idiosyncratic rather than dose-related, so it cannot be prevented by dose alone; the PRR here is very high for a rare event, and the modest absolute count reflects how uncommon agranulocytosis is even among treated patients.

Regulatory basis: methimazole and propylthiouracil prescribing information (agranulocytosis warning; fever/sore-throat counselling). Established antithyroid-drug agranulocytosis literature.

Bradford Hill viewpoint	Status	Note
Temporality (necessary)	met	Typically appears within weeks–months of starting the drug
Strength	met	PRR 38 for a rare, serious event
Consistency	met	A long-recognized class effect of antithyroid drugs
Specificity	met	Among the defining serious risks of methimazole and propylthiouracil
Biological gradient	not established	Idiosyncratic — not clearly dose-related
Plausibility	partial	An immune-mediated mechanism is accepted; the precise target is not fully mapped
Coherence	met	Coheres with the label warning and the fever/sore-throat counselling
Experiment	partial	Recovery on withdrawal and G-CSF support is consistent; no randomized test
Analogy	met	Analogous to clozapine- and sulfonamide-associated agranulocytosis

This page's own qualitative read, not an automated/citation-gated assessment.

✗ No ClinicalTrials.gov results-posting trial surfaced for methimazole with agranulocytosis as a tracked event — the drug is used in routine endocrine practice rather than in large registered trials, and the reaction is too rare for the studies that do exist to capture. The evidence base is decades of clinical case series and the prescribing information, not trial AE data.