Gabapentin – Dosage information for RLS, Epilepsy and Postherpetic Neuralgia

The Gabapentin dosage differs in each individual depending upon the age of the person, current medical condition and patient’s tolerance to the medicine. This article will help you know about the general Gabapentin dosage information for RLS, Epilepsy and Postherpetic Neuralgia.

Again the dosage can differ thus you should take Gabapentin as recommended by your doctor.

Normal Dose for Epilepsy- In Adults

Initial dose: 300mg to be taken orally on first day

300 mg to be taken orally two times a day on the second day

300mg to be taken orally thrice a day on third day

Maintenance dose: 300-600mg to be taken orally thrice a day

Maximum dose: 3600mg to be taken orally daily in 3 split doses

Maximum time gap between doses in a schedule wherein the patient is taking the medicine thrice a day should not be more than 12 hours

Note:  Gabapentin can be taken with/without food

If you have not used the half tablets (broken) within 28 days after breaking, the tablet should be disposed.

Normal Dose for Postherpetic Neuralgia – In Adults

Initial dose: 300mg to be taken orally on first day

300 mg to be taken orally two times a day on the second day

300mg to be taken orally thrice a day on third day

The dosage can be adjusted as required

Maintenance dose: 1800mg/day (600mg to be taken orally three times a day)

Note: Gabapentin can be taken with/without food

If you have not used the half tablets (broken) within 28 days after breaking, the tablet should be disposed

Gabapentin available under the brand name GRALISE(R)

Maintenance dose: GRALISE(R) should be adjusted to 1800mg to be taken orally once in a day during meal.

Recommended dosage schedule

Day 1: 300 mg to be taken orally with meal in the evening

Day 2: 600 mg to be taken orally with meal in the evening

From Day 3 to day 6: 900 mg to be taken orally with meal in the evening

From Day 7 to day 10: 1200 mg to be taken orally with meal in the evening

From Day 11 to day 14: 1500 mg to be taken orally with meal in the evening

Day 15: 1800 mg to be taken orally with meal in the evening

Gabapentin (enacarbil extended release tablets) are sold under brand name HORIZANT (R)

The recommended dosage – 600 mg to be taken orally twice a day

Therapy should be started at a dose of 600mg to be taken orally in the morning till 3 days of therapy and can be increased up to 600mg to be taken twice a day and 1200 mg/day on fourth day.

Normal Dose for Restless Leg Syndrome- In Adults

600mg to be taken orally once daily during 5 PM with food

The medication is used to treat mild to severe RLS in adults

The above dosage information is general dosage information that can vary from person to person depending upon his/her medical condition and age. Your doctors can advice the right dose for you. [1]

Appropriate Gabapentin Dosing for Neuropathic Pain

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.1,2 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.3 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.4,5

Several cross-sectional studies have reported gabapentin being used in subtherapeutic doses among most patients.6-8 In a retrospective analysis of 939 patients with post-herpetic neuralgia, the mean daily dose of gabapentin was 826 mg.7 In another 2-year retrospective study of 151 veterans with various neuropathic pain syndromes, the median daily dose for gabapentin was 900 mg.8 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.

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.

Gabapentin is Used for Neuropathic Pain (other than Postherpetic Neuralgia)

In a meta-analysis of trials evaluating the treatment of neuropathic pain, including painful polyneuropathy and spinal cord injury pain, gabapentin was shown to be safe and effective .

Data from meta-analyses support the use of immediate-release gabapentin for reducing pain by more than 50% in diabetic neuropathy.

 

Diabetic Peripheral Neuropathy
Diabetic Peripheral Neuropathy

Data from a limited number of clinical trials support the use of extended-release gabapentin in reducing pain by more than 50% and improving sleep in diabetic neuropathy.

Gabapentin (Neurontin) has FDA indication to treat postherpetic neuralgia and partial onset seizures.  Controlled clinical trials in diabetic neuropathy and postherpetic neuralgia show that gabapentin at 2400-3600 mg/day has a similar efficacy to tricyclic antidepressants and carbamazepine.  Consistent, though less compelling clinical evidence supports its use for neuropathic cancer pain, pain associated with HIV infection, chronic back pain and others (readers wanting more in depth research findings are urged to consult Reference 1).

Due to this emerging evidence, it is widely used for the treatment of neuropathic pain.  The exact mechanism and site of action of gabapentin is unknown.   Gabapentin is generally well-tolerated, easily titrated, has few drug interactions, and does not require laboratory monitoring.  However, cost may be a limiting factor for some patients.

Patients suitable for gabapentin should have a clear neuropathic pain syndrome, characterized by sharp, shooting, lancinating and/or burning pain, in a nerve root (radicular) or stocking/glove distribution. See Fast Fact #289 for a comparison of gabapentin with pregabalin a similar neuropathic analgesic.

Adult Dosing    Gabapentin is started at low doses (100 mg to 300 mg total daily) and increased by 100 – 300 mg every 1-3 days to effect.  A typical schedule might be: day 1-2: 300 mg nightly; day 3-4: 300 mg twice daily; day 5-7: 600 mg twice daily; day 8 onwards: 600 mg three times a day.  The usual effective total daily dose is 900-3600 mg, administered in three divided doses per day.  Titration should proceed more slowly in elderly patients. If gabapentin is discontinued, it should be done over a minimum of a week to prevent withdrawal seizures.

Pediatric Use    There is limited data available assessing its effectiveness in neuropathic pain in children. The American Pain Society recommends that gabapentin be considered for pediatric neuropathic pain especially when concurrent analgesics are found to be too sedating.  Their recommended initial dose is 2 mg/kg/day with a usual dosage range of 8 to 35 mg/kg/day divided into 3 daily doses.

Dosing in Renal Failure   Gabapentin doses must be reduced for patients with renal insufficiency.

  • Creatinine Clearance (CrCl) 30-60 ml/min: maximum daily dose is 1400 mg, divided.
  • CrCl 16-30 ml/min: maximum daily dose is 700 mg, given once daily.
  • CrCl 15ml/min: maximum daily dose is 300 mg, once daily.  Doses should decrease proportionally for CrCl less than 15 ml/min (e.g. 300 mg every other day for a CrCl of ~7.5 ml/min).
  • For patients on hemodialysis a supplemental dose is usually given after dialysis (usually 100-300 mg).

Adverse Reactions    Sedation, confusion, dizziness, and ataxia are the most common side effects, especially with rapid dose titration.  Tolerance to these effects appears to develop within a few days if the dose is held at the highest tolerated dose until symptoms improve or stabilize.

Dosage Formulations    Gabapentin is available in 100 mg, 300 mg, and 400 mg capsules, 600 mg and 800 mg tablets, and as a liquid (250mg/5mL).

Cost    Gabapentin is more expensive than older agents used for neuropathic pain (tricyclic antidepressants and older anti-epileptic drugs such as carbamazepine).  Generic gabapentin is available, although can cost ~$100 for 90 600 mg tablets.

Other Palliative Care Uses of Gabapentin    Small scale published trials have shown efficacy in the treatment of severe chronic hiccups, pruritus, postoperative pain and delirium, restless leg syndrome and hot flashes. Perhaps more compelling is its potential efficacy for chronic cough for which a randomized double-blind placebo controlled trial demonstrated significant improvement in cough-specific quality of life, cough frequency, and cough severity. See Fast Fact #200.

Summary    Gabapentin is a safe and effective adjuvant analgesic for neuropathic pain.  Physicians should become comfortable using and titrating gabapentin in patients with neuropathic pain syndromes.

Based on guidelines from the International Association for the Study of Pain (IASP), European Federation of Neurological Societies (EFNS), and Society of Critical Care Medicine (SCCM), gabapentin is effective and recommended for the management of peripheral neuropathy .

Based on guidelines from the EFNS, IASP, and National Institute for Health and Care Excellence (NICE), gabapentin is effective and recommended as first-line therapy, supported by strong evidence, in the management of diabetic neuropathy.

The IASP guidelines recommend both immediate- and extended-release gabapentin . In contrast, a guideline from the American Academy of Neurology (AAN), American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation states that gabapentin is probably effective and should be considered an alternative treatment for painful diabetic neuropathy based on limited benefit in 2 controlled trials.

Similarly, a position statement from the American Diabetes Association (ADA) recommends gabapentin as a second-line option .