INTRODUCTION: The Orphan Drug Act encourages drug development for rare 
conditions. However, some orphan drugs become top sellers for unclear reasons. 
We sought to evaluate the extent and cost of approved and unapproved uses of 
orphan drugs with the highest unit sales.
METHODS: We assessed prescription patterns for four top-selling orphan drugs: 
lidocaine patch (Lidoderm) approved for post-herpetic neuralgia, modafinil 
(Provigil) approved for narcolepsy, cinacalcet (Sensipar) approved for 
hypercalcemia of parathyroid carcinoma, and imatinib (Gleevec) approved for 
chronic myelogenous leukemia and gastrointestinal stromal tumor. We pooled 
patient-specific diagnosis and prescription data from two large US state 
pharmaceutical benefit programs for the elderly. We analyzed the number of new 
and total patients using each drug and patterns of reimbursement for approved 
and unapproved uses. For lidocaine patch, we subcategorized approved 
prescriptions into two subtypes of unapproved uses: neuropathic pain, for which 
some evidence of efficacy exists, and non-neuropathic pain.
RESULTS: We found that prescriptions for lidocaine patch, modafinil, and 
cinacalcet associated with non-orphan diagnoses rose at substantially higher 
rates (average monthly increases in number of patients of 14.6, 1.45, and 1.58) 
than prescriptions associated with their orphan diagnoses (3.12, 0.24, and 0.03, 
respectively (p<0.001 for all)). By contrast, for imatinib, approved uses 
increased significantly over off-label (0.97 vs. 0.47 patients, p<0.001). 
Spending on off-label uses was highest for lidocaine patch and modafinil (>75%). 
Increases in lidocaine patch use for non-neuropathic pain far exceeded 
neuropathic pain (10.2 vs. 3.6 patients, p<0.001).
DISCUSSION: In our sample, three of four top-selling orphan drugs were used more 
commonly for non-orphan indications. These orphan drugs treated common clinical 
symptoms (pain and fatigue) or laboratory abnormalities. We should continue to 
monitor orphan drug use after approval to identify products that come to be 
widely used for non-FDA approved indications, particularly those without 
adequate evidence of efficacy.