What is gabapentin?
Gabapentin is an anti-epileptic drug, also called an anticonvulsant. It affects chemicals and nerves in the body that are involved in the cause of seizures and some types of pain.
All brands of gabapentin are used in adults to treat neuropathic pain (nerve pain) caused by herpes virus or shingles (herpes zoster).
The Gralise brand of gabapentin is indicated for the management of neuropathic pain only. It is not used for epilepsy.
The Horizant brand of gabapentin, in addition to treating neuropathic pain, is also used to treat restless legs syndrome (RLS).
The Neurontin brand of gabapentin is also used to treat seizures in adults and children who are at least 3 years old, in addition to neuropathic pain.
Use only the brand and form of gabapentin your doctor has prescribed. Check your medicine each time you get a refill to make sure you receive the correct form.
Some people have thoughts about suicide while taking this medicine. Children taking gabapentin may have behavior changes. Stay alert to changes in your mood or symptoms. Report any new or worsening symptoms to your doctor.
Do not stop using gabapentin suddenly, even if you feel fine.
Before taking this medicine
You should not use gabapentin if you are allergic to it.
To make sure this medicine is safe for you, tell your doctor if you have ever had:
- kidney disease (or if you are on dialysis);
- depression, a mood disorder, or suicidal thoughts or actions;
- a seizure (unless you take gabapentin to treat seizures);
- liver disease;
- heart disease; or
- are taking an anti-depressant or sedating medication; or
- (for patients with RLS) if you are a day sleeper or work a night shift.
Some people have thoughts about suicide while taking this medicine. Your doctor should check your progress at regular visits. Your family or other caregivers should also be alert to changes in your mood or symptoms.
It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.
Seizure control is very important during pregnancy, and having a seizure could harm both mother and baby. Do not start or stop taking gabapentin for seizures without your doctor’s advice, and tell your doctor right away if you become pregnant.
Neuropathic pain is a chronic debilitating pain syndrome that is complex to treat. Current medication management for neuropathic pain includes select neuromodulating agents such as anticonvulsants, serotonin norepinephrine reuptake inhibitors, tricyclic antidepressants, and certain opioids. Gabapentin remains among the most commonly used anticonvulsants for neuropathic pain.
The established therapeutic dosing for gabapentin in neuropathic pain trials is 1800-3600 mg/day in 3 divided doses in patients with normal renal function. This means the minimum effective dose is 600 mg 3 times a day. Renal adjustments are recommended in patients with CrCl below 60 mL/min. For patients on dialysis, gabapentin can often be 3 times weekly following dialysis.
Several cross-sectional studies have reported gabapentin being used in subtherapeutic doses among most patients.
In a retrospective analysis of 939 patients with post-herpetic neuralgia, the mean daily dose of gabapentin was 826 mg. In another 2-year retrospective study of 151 veterans with various neuropathic pain syndromes, the median daily dose for gabapentin was 900 mg. In both studies, the most prevalent gabapentin dosing was half the therapeutic dosing.
The cornerstones of effective pharmacotherapy are the right patient, the right drug, and the right dose. If an analgesic medication is being used at a suboptimal dose, oftentimes a knee-jerk reaction is to add another analgesic for synergy. While this may well be indicated under appropriate circumstances, it is inappropriate without maximizing the dose of each single agent with careful attention to dose titration in order to minimize toxicity of each add-on. Consider for example a patient who starts low dose gabapentin that was not properly titrated, returns for follow-up and is given an additional prescription for duloxetine for neuropathic pain since gabapentin “does not work,” assuming there are no tolerability issues.
This adds to polypharmacy, increased costs, and the pain remains inadequately treated.
Pharmacists as medication experts can collaborate with prescribers to optimize the rational use of gabapentin in neuropathic pain. First, let’s take a look into the pharmacology of gabapentin.
Gabapentin is a gaba aminobutyric acid (GABA) analogue anticonvulsant but does not exhibit any significant agonistic effects at the GABA receptor. Gabapentin inhibits the alpha-2-delta subunit of the N-type voltage-gated calcium channels. Receptor binding causes presynaptic inhibition of excitatory neurotransmitter release (i.e. glutamate) thereby attenuating neuropathic pain.
Gabapentin’s counterpart, pregabalin, shares the same mechanism of action but there are key pharmacologic differences between both medications. Gabapentin has saturable, non-linear absorption kinetics, where bioavailability decreases as the dose increases.10 Following oral administration, gabapentin’s bioavailability is 60%, 47%, 34%, and 33%, following 900, 1200, 2400, and 3600 mg/day in 3 divided doses, respectively. On the other hand, pregabalin has ≥90% bioavailability irrespective of the dose, leading to more predictable kinetics. Pregabalin boasts a binding affinity for the alpha-2-delta receptor that is six times greater than that of gabapentin.
What Every Patient Should Know
Patients should be aware of the therapeutic dosing for neuropathic pain to establish realistic expectations and improve compliance and likelihood of remaining on therapy. The conversation may be as follows: “Gabapentin may reduce nerve pain at 600 mg 3 times a day but patients usually start on a low dose to make sure they tolerate it and is then increased slowly to give the body a chance to get used to it. If dose increases along the titration cause intolerable side effects such as dizziness or drowsiness, this can often be overcome by reducing back to the previous dose and escalating more slowly over a longer period of time.” Patients should be encouraged to follow-up with their prescriber for continued titration.
Gabapentin Is Not a “PRN” Medication
Another mishap with gabapentin that contributes to treatment failure is when patients take it on an as needed basis. Gabapentin exhibits its activity by impeding calcium trafficking and is required to be present at the alpha-2-delta receptor for 17-20 hours in order to ensure efficacy.11 Therefore, gabapentin needs to be taken around the clock to exert its analgesic effects rather than used on an as needed basis. This is another area that pharmacists can educate patients at initiation of therapy to improve compliance.
Despite its therapeutic role in neuropathic pain, gabapentin produces psychoactive effects and has an abuse liability. Gabapentin abuse typically involves taking higher doses in a single administration. The median single dose for gabapentin abuse is 3600 mg, which is 3 times the maximum recommended single dose of 1200 mg.12 Risk factors for gabapentin abuse include current or previous opioid abuse, previous cocaine use, and/or concurrent use of benzodiazepines or cannabis. Alcohol use disorder is not generally a predictor of gabapentin abuse.12
In conclusion, pharmacists as medication experts are well-poised to educate prescribers and patients on therapeutic dosing of gabapentin to optimize its rational and appropriate use for treating neuropathic pain.