Topical phenytoin gains momentum

In a recent overview, published in the Pubmed indexed peer reviewed journal ‘Pain Management’ of November 2017: Management of chronic neuropathic pain with single and compounded topical analgesics’ a number of references to the work of Topical Innovations on phenytoin cream can be found.

In the introduction of the paper we find as a separate bullet:

  • Phenytoin 10% cream, a nonselective voltage-gated Na channel stabilizer, GABA receptor agonist, showed promising results in allodynia reduction.

The phenytoin cream and the work on the keratinocyte hypothesis is referenced at multiple paragraphs, and in table 3:

Table 3. ‘Topical compounds: gabapentin, phenytoin and baclofen for peripheral neuropathy’, where we can read on phenytoin:


– Nonselective voltage-gated Na channel stabilizer
– Dose-dependent inhibition of sodium channel Nav1.7 (which is present in the epidermal-free nerve ending)
– Inhibits voltage dependent L-type Ca2+ channels
– GABAA receptor agonist
– Decreases the synaptic excitation through NMDA receptor antagonism
– Possible reduction of conduction velocity in unmyelinated C fibers
– Gingiva and skin might play a role in the extra-hepatic site metabolism

In the same table, various reports of clinical effects of phenytoin cream are summarized:

– Phenytoin 5% cream reduced allodynia for 8 h in a patient with diabetic neuropathic pain and phenytoin 10% cream completely relieved the symptoms for more than 12 h in the same patient
– A patient with combined chronic idiopathic axonal polyneuropathy had a pain score decrease from 8 to 3 on NRS following phenytoin 5% cream application that lasted for at least 5 h

– Chemotherapy-induced polyneuropathy patient compared the pain reduction with baclofen 5% cream and phenytoin 5% cream: 7–3 (NRS) and 7–0 (NRS), respectively. Phenytoin 10% increased the effect duration from 4 h to 6 h, compared with phenytoin 5% in the same patient

– Phenytoin 10% cream for trigeminal neuralgia patient and post-herpetic neuralgia patient showed superiority over the control ketamine 10% cream in both cases

Clearly this is a new sign that the work on phenytoin cream in neuropathic pain is receiving international recognition.

Source: Knezevic NN, Tverdohleb T, Nikibin F, Knezevic I, Candido KD. Management of chronic neuropathic pain with single and compounded topical analgesics. Pain Manag. 2017 Nov 10. doi: 10.2217/pmt-2017-0020.