Pregabalin
Second line gabapentinoid
Mechanism of action: Gabapentin displays high affinity binding to the alpha2-delta subunits of voltage-gated calcium channels in central nervous system neurones, thus reducing the release of neurotransmitters. It is a chemical analogue of GABA but has no activity in GABAergic neuronal systems.
Presentation: capsule (which can be opened, and the contents sprinkled onto food or dissolved in water if needed). Oral solution not available in OUH.
Suggested initial dose: 75mg twice a day for adults over 50kg with normal hepatic and renal function; reduce in frailty to 25mg twice a day. Maximum dose 600mg per day in 2-3 divided doses.
Avoid abrupt withdrawal.
It usually takes 4-7 days for the analgesic effect to become clinically beneficial.
Caution: Pregabalin has been associated with infrequent reports of severe respiratory depression, including some cases without the presence of concomitant opioid medicines. Patients with compromised respiratory function, respiratory or neurological disease, renal impairment; those using concomitant central nervous system (CNS) depressants; and people older than 65 years might be at higher risk of experiencing these events and adjustments in dose or dosing regimen may be necessary. https://www.gov.uk/drug-safety-update/pregabalin-lyrica-reports-of-severe-respiratory-depression
Oral absorption: Bioavailability of greater than 90%. Rapid absorption with maximum concentrations achieved within 1 hour. It is absorbed mainly in the small intestine but absorption continues in the proximal colon.
Protein binding: Pregabalin does not bind to plasma proteins
Metabolism: Pregabalin undergoes negligible metabolism
Elimination: mainly renal excretion of unchanged drug
Reduce dose in renal failure.
Half-life: 6 hours
Further prescribing information (side effects, contraindications, interactions):
Concerns about the potential for abuse, usually at doses far exceeding those in pain management, have surfaced in the last few years, particularly amongst intravenous drug users and prison populations. Pregabalin appears to have a higher abuse potential than gabapentin. Prescribers need to be aware that the gabapentinoids thus have a 'street value', and caution should be exercised if prescribing for patients with a history of drug abuse.