Gabapentinoids

Gabapentin

• First discovered in 1970s in an attempt to create a GABA analogue
• Whilst it resembles GABA, it does not act on the GABA receptor.
• Later discovered to act on α2δ subunits of voltage-dependent calcium channels to reduce calcium influx
  • Precise mechanism of analgesia unclear

• Inhibits release of excitatory neurotransmitters: glutamate, NA, substance P
• Medsafe licenced for: neuropathic pain, adjunct anti-epileptic
• Pharmacokinetics
  • Absorption: Saturable transporter so delayed peak levels at higher doses. Drugs that reduce motility (e.g opiates) increase bioavailability. Peak serum conc 3 hours
  • Distribution: Less lipophilic so requires active transport across the BBB
  • Metabolism: minimal
  • Elimination: Renal excretion, half life 5-7 hours. Dose adjustment in renal impairment

Pregabalin

• Similar to gabapentin. Binds to α2δ subunits of voltage-dependent calcium channels to reduce calcium influx
  • Inhibits release of excitatory neurotransmitters: glutamate, NA, substance P
• Medsafe licenced for: neuropathic pain, adjunct anti-epileptic
• Pharmacokinetics
  • Absorption: Rapid absorption after oral administration. Peak serum conc 1h
  • Distribution: Less lipophilic so requires active transport across the BBB
  • Metabolism: minimal, no active metabolites
  • Elimination: Renal excretion, half life 6.3 hours. Dose adjustment in renal impairment

Recommended prescribing: NZF

Gabapentin

• Day 1 300mg nocte
• Day 2 300mg bd
• Day 3 300mg tds
• Then increase by 300mg every 2-3 days to max dose 3600mg daily

Pregabalin

• Initially 75mg bd
• 150mg bd after 3-7 days
• Max dose 300mg bd after further 7 days

Titrate upwards until pain relief, side effects, or max dose reached

Remember to dose adjust for renal impairment: gabapentin if <80mL/min, pregabalin if <60mL/min

Caution in pregnancy (category B1); no clear data available,  use if benefits outweigh risks

Evidence

Post-herpetic neuralgia, diabetic peripheral neuropathy and fibromyalgia