Gabapentinoids
From WikiMSK
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 ฮฑ2ฮด 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 ฮฑ2ฮด 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
- Moderate quality evidence supports the use of gabapentinoids to improve pain in those with post-herpetic neuralgia or diabetic peripheral neuropathy compared with placebo [1] [2]
- High quality evidence supports the use of pregabalin to improve pain in those with fibromyalgia compared to placebo [3]
- The evidence for gabapentin in fibromyalgia is unclear because of the small number of trials and very low quality of evidence available [4]
Low back and radicular pain
- Systematic review and meta-analysis of 7 RCTs compared gabapentin and pregabalin to placebo. Judged moderate-high quality data [5]
- Low back pain with or without lumbar radicular pain
- No difference in pain or disability at short, intermediate or long term follow up
- Lumbar radicular pain only
- No difference in pain or disability at short, intermediate or long term follow up
- โ Derry et al.. Pregabalin for neuropathic pain in adults. The Cochrane database of systematic reviews 2019. 1:CD007076. PMID: 30673120. DOI. Full Text.
- โ Wiffen et al.. Gabapentin for chronic neuropathic pain in adults. The Cochrane database of systematic reviews 2017. 6:CD007938. PMID: 28597471. DOI. Full Text.
- โ Derry et al.. Pregabalin for pain in fibromyalgia in adults. The Cochrane database of systematic reviews 2016. 9:CD011790. PMID: 27684492. DOI. Full Text.
- โ Cooper et al.. Gabapentin for fibromyalgia pain in adults. The Cochrane database of systematic reviews 2017. 1:CD012188. PMID: 28045473. DOI. Full Text.
- โ Enke et al.. Anticonvulsants in the treatment of low back pain and lumbar radicular pain: a systematic review and meta-analysis. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 2018. 190:E786-E793. PMID: 29970367. DOI. Full Text.
