- Neuropathic pain
- Focal seizures
- Gabapentin may be used as monotherapy
- Pregabalin is licensed as an adjunctive therapy only
- Gabapentin is licensed for treatment of other symptoms such as:
- Spasticity in multiple sclerosis
- Oscillopsia in multiple sclerosis
- Menopausal symptoms (esp. hot flushes) in women with breast cancer
- Muscular symptoms in motor neurone disease
- Pregabalin is also licensed for generalised anxiety disorder
Gabapentinoids
Gabapentinoids
- The gabapentinoids comprise of gabapentin and its specifically designed successor pregabalin
- Pregabalin shares many features with gabapentin, but benefits from:
- Higher receptor affinity
- BD dosing schedule (vs. TDS)
- Easier titration
Presentation
- Both gabapentin and pregabalin preesnt as tablets, capsules or as an oral solution
Dosing
- Gabapentin is started at doses of 100-300mg TDS, which are then uptitrated over time
- The maximum dose depends on whether the indication is neuropathic pain (max. 3.6g/day), seizures (4.8g/day) or other symptoms (lower max. doses)
- Pregabalin is started at doses of 25mg-75mg BD, which are then uptitrated over time
- Maximum dose of pregabalin is 1800mg/day in divided doses
- Inhibitory action via binding to the ɑ2δ-1 protein
- The ɑ2δ-1 protein was initially considered to be an auxiliary subunit of pre-synaptic, voltage-gated calcium channels
- It has since been shown to interact with a wider set of membrane proteins, including NMDA glutamate receptors
- Inhibition of the protein impairs nociceptive signalling in the dorsal horn of the spinal cord
- Other mechanisms:
- Partially reduce glutamatergic action at the NMDA receptor
- Stimulate glutamate decarboxylase (i.e. stimulates creation of GABA)
- Enhance synaptic release of GABA
Absorption
- Gabapentin has 60% oral bioavailability that decreases with increasing doses
- Pregabalin has better bioavailability (90%) that is not affected by dose, although absorption is delayed by food
Distribution
- Neither drug is bound to plasma proteins, which makes them less likely to interact with other drugs that are protein bound
- This is a big positive feature as patients with neuropathic pain or epilepsy may be taking a large array of other medications
- Gabapentin VD of 0.85L/kg
- Pregabalin has a lower VD of 0.6L/kg
Metabolism
- Undergo little-to-no metabolism
- Therefore safe in hepatic impairment
Excretion
- Both entirely renally excreted with an elimination half life of 6hrs
- Therefore reduced dose required in renal dysfunction
- Are removed by haemodialysis
Neurological
- May cause development of psychiatric symptoms
- Other CNS effects include ataxia, dizziness, fatigue, nausea, vomiting and fever
- Enhanced mood
- Improved sleep patterns
Renal
- Reduced dose required in renal dysfunction
Gastrointestinal
- GI upset more common with pregabalin
Metabolic
- Weight gain, erectile dysfunction and leukopaenia may also occur
- May increase risk of viral infections