I take 600 mg of neurontin 3 times a day. It helps my pain to some extent. I can't take a higher dose as I get way too sleepy and out of it! My problem is that after about 6 hours or so my pain gets really bad and I have to go through those 2 hours with bad pain until I can take it again. I wondered if you can take Neurontin every 6 hours instead? I was thinking about trying 400 mg every 6 hours instead but wondered if that would be OK. Any help or advice would be appreciated! Thanks.
my 2 cents
not a doctor but was a 2 year user of neurontin, finishing at 3200mg a day 4 x 800,
i found this on a site like this devoted to neurontin, and wen iwent from 3x to 4x aday the pain control was indeed better .
the site and mailing list i used to go to isFor optimal dosing, Neurontin should be divided into a four (or more) times a day frequency to keep a constant blood level. If one is taking Neurontin on a three (or less) times a day and is experiencing break-through pain, the easiest experiment (with the doctor's permission) would be to divide the daily dose into four equal doses to see if that solves the problem.
neurontin site/mailing list
hope this helps, i have found that learning as much as possible is neccessary with this, they also recommend having a small piece of protein with your dose to offset carbo carving and sleepiness. its worth a try
Thanks Yonkersguy! That web site is interesting and helpful. I'm glad to hear that taking it 4 times a day is ok. I may try the 400 mg 4 times a day and see what happens. I doubt I could manage if I took 600 mg 4 times a day. I'm sleepy enough as it is now and I definitely have the brain fog! Thanks again-you were a big help!
Phillis and Yonkersguy,
Let me summarize some of the published data on use of high-dose gabapentin. Although these studies have mostly been for treatment of epilepsy, the adverse events profile of the drug probably should be similar for people with neuropathic pain.
There is not all that information about the pharmacokinetics of very high dose gabapentin (GBP) in the range of 3000-5000 mg per day.
Berry, et al. (2003) looked at high dose (1200-4800 mg/day) gabapentin per day in patients with epilepsy. They found that gabapentin continues to be absorbed in a "reasonably linear manner in doses up to 4800 mg per day (it may do so at higher doses but I don't think that they tested it).
Lindberger, et al. (2003) recently studied the serum concentrations of gabapentin. The patients were started on 1800 mg/day and the dose was increased stepwise to 2,400 and 3,600 mg/day. They found that 1800 mg/day produce serum concentrations of 26±12 µmol.
Singh & Kennedy (2003) studied the effects of gabapentin treatment of postherpetic neuralgia (a pain problem). Gabapentin apparently in not linearly absorbed, <3% is bound by protein, and is high distributed all over the body. It is excreted from the kidney without being metabolized, suggesting that drug clearance depending on renal clearance. Dizziness and somnolence were the most frequent side-effects leading to withdrawal. The recommended dosage is 300 mg at bedtime on day 1, 300 mg twice a day on day 2, 300 mg three times a day, and titrating as needed to 2400-3600 mg/day.
Beran, et al. (2001) titrated patients up to a maximum of 4,800 mg/day over 24 weeks in 176 patients. The most frequent adverse event were dizziness (31%), fatigue (29%), headache (21%), and ataxia (20%). These adverse events did increase to the point that treatment discontinuation was necessary as the drug levels were increased.
McLean, et al. (1999) had carried out a study comparing patients being treated with <1800 mg/day and >1800 mg/day. A total of 281 patients were studied. Three adverse events (asthenia, headache, dizziness) were observed in more patients at the lower dose group. Overall, in a population of 2216 patients, they found that only 10.6% of the patients prematuraly withdrew due to adverse events and 3.5% withdrew due to ineffectiveness of the drug to control seizures. The authors conclude that gabapentin doses of >1800 mg/day are as well tolerated as those <=1800 mg/day, and well not associated with more adverse events. Note that this is slightly misleading because the patients were titrated to higher doses based on tolerance of the drugs. Those that could not tolerate 1800 or higher probably remained in the lower dose group while those who could tolerate the drug had relatively few adverse events. In other words, those who could tolerate it tolerated it well.
Beydoun, et al. (1998) treated patients with epilepsy with doses up to 4,800 mg per day in 45 patients. In this open-label study, the average daily dose of gabapentin was 3,900 mg/day and mean followup period was 252 days. The most common adverse event was tiredness, sleepness, and these were not dose related. In other words, if you don't have these problems on lower doses, you are unlikely to have them at higher doses.
In summary, high-dose gabapentin has been used to treat many people. Its major side-effects are somnolence and dizziness, affecting perhaps 20-40% of people. Interestingly, these side-effects are not dose-related. People are either tolerant or not so tolerant of the drug. If somebody does not have side effects at <1800 mg/day, going above 1800 mg/day does not seem to result in complications. There is no information concerning taking it 3 or 4 times a day although at least one study suggests that twice a day may be effective.
References Cited
• Berry DJ, Beran RG, Plunkeft MJ, Clarke LA and Hung WT (2003). The absorption of gabapentin following high dose escalation. Seizure 12:28-36. Summary: Gabapentins (GBP) is structurally similar to GABA yet its mode of action remains uncertain. It is water-soluble and GI tract absorption occurs via the L-amino acid transport system in the proximal small bowel. It has been suggested that this transportation is capacity limited, thus decreasing GBP bioavailability at higher doses. GBP is not protein bound, therefore, salivary levels might be expected to be similar to those in serum; also the drug does not induce hepatic enzymes and is excreted unmetabolised by the kidney. Within the dose-range normally prescribed, it is devoid of pharmacokinetic (PK) drug interactions with all other anti-epileptic drugs. This study assesses two things in patients with epilepsy: (a) bioavailability of higher doses of GBP (1200-4800 mg per day), and (b) the influence of high dose GBP on between-dose serum concentrations of co-prescribed anti-epileptic drugs. After stabilising at each dosage, a sequence of serum and saliva samples were collected within the dosage interval; GBP and co-medication concentrations were determined and the results subjected to PK modelling. Meaned results from 10 patients indicate that GBP continues to be absorbed in a reasonably linear manner relative to dose up to 4800 mg per day. The study also shows that GBP is transported into saliva, however, salivary concentrations are only 5-10% of those in plasma. Furthermore, the results indicate that GBP, in higher than recommended doses, did not change plasma concentrations of lamotrigine, carbamazepine, carbamazepine-epoxide, vigabatrin, primidone, phenobarbitone or phenytoin when added to treatment.It is concluded that larger than recommended doses of GBP can be efficiently absorbed by some patients and also that GBP plasma levels do not fluctuate greatly between dosage intervals, therefore, twice daily dosage is a possibility. Medical Toxicology Unit, Guy's & St. Thomas Hospital Trust, Avonley Road, London SE14 5ER, UK.
• Lindberger M, Luhr O, Johannessen SI, Larsson S and Tomson T (2003). Serum concentrations and effects of gabapentin and vigabatrin: observations from a dose titration study. Ther Drug Monit 25:457-62. Summary: To explore possible concentration-effect relationships, gabapentin (GBP) and vigabatrin (VGB) serum concentrations were obtained from patients participating in an add-on dose-titration trial comparing GBP and VGB in partial epilepsy. Patients randomized to GBP started on 1800 mg/d and could have their dosage increased stepwise to 2400 and 3600 mg/d if seizures persisted. Those randomised to VGB started on 1000 mg/d, and the dose could be increased to 2000 and 4000 mg/d. Blood samples were obtained at steady state, at a nonstandardized time, from 27 patients randomized to GBP and from 36 randomized to VGB. Serum samples were analyzed using high-performance liquid chromatography. The treatment effect was expressed as percentage reduction in number of seizures from baseline. In addition, patients were classified as responders (>50% reduction in number of seizures from baseline) or nonresponders. There was no significant correlation between serum concentrations of GBP and seizure reduction at the lowest dosage, 1800 mg/d (r = -0.02, P = 0.94, Spearman-rank), nor between VGB serum levels and seizure reduction at 1000 mg/d of VGB (r = -0.14, P = 0.44). The serum GBP concentrations among responders to GBP 1800 mg/d were 26 +/- 12 micro mol/L (mean +/- SD), which was not different from serum concentrations in nonresponders, 28+/-13 micro mol/L. Nor was there a difference between serum concentrations of responders and nonresponders to VGB 1000 mg/d (32 +/- 23 and 44 +/- 36 micro mol/L, respectively). Hence, with the present study design we were unable to identify specific target ranges of GBP and VGB serum concentrations. Department of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden. martin.lindberger@neuro.hs.sll.se.
• Singh D and Kennedy DH (2003). The use of gabapentin for the treatment of postherpetic neuralgia. Clin Ther 25:852-89. Summary: BACKGROUND: Varicella-zoster virus causes chickenpox and can reemerge later in life to cause herpes zoster or shingles. One of the most common and disabling complications of herpes zoster is postherpetic neuralgia (PHN). OBJECTIVES: This article reviews the current primary literature about the efficacy and tolerability of gabapentin for the treatment of PHN. Gabapentin pharmacokinetics and drug interactions are also reviewed. METHODS: A literature search in the English language was conducted using OVID Web, which contained the following databases: MEDLINE (1966-present), EMBASE (1980-2002), Current Contents/Clinical Medicine (1999-2002), Cochrane Controlled Trials Register (1898-present), Cochrane Database of Systemic Reviews (fourth quarter, 2002), and International Pharmaceutical Abstracts (1970-2002). Search terms used were postherpetic neuralgia; zoster; gabapentin; neuropathic pain; pain; pharmacoeconomic; cost; controlled clinical trial; randomized, controlled trial; postherpetic neuralgia and gabapentin; gabapentin and pain; treatment and postherpetic neuralgia; gabapentin and age; gabapentin and gender; gabapentin and ethnicity; and gabapentin and pharmacokinetics. RESULTS: Gabapentin displays nonlinear absorption kinetics, is minimally protein bound (< 3%), has a high mean [SD) volume of distribution [50.4 [8.0] L), and is excreted via the kidneys as unchanged drug. Two randomized, placebo-controlled, parallel-group, multicenter clinical trials demonstrated the effectiveness of gabapentin at doses of up to 3600 mg/d to significantly reduce pain [P < 0.01 and P < 0.001), improve sleep [P < 0.01), and improve some parameters on the Short Form-McGill Pain Questionnaire [P < 0.05). Dizziness and somnolence were the most common side effects leading to withdrawal from the trials. The recommended dosage in adults is 300 mg at bedtime on day 1,300 mg BID on day 2, and 300 mg TID on day 3, titrating up as needed to 2400 to 3600 mg/d. To reduce adverse events in patients with renal impairment, the dose should be adjusted based on the patient's creatinine clearance. CONCLUSIONS: Gabapentin appears to be effective and well tolerated for the short-term treatment of PHN. However, future controlled studies are needed to determine whether the effectiveness of gabapentin for PHN is maintained for > 2 months, to establish the optimal dose of gabapentin for PHN, and to compare the efficacy of gabapentin with that of other pharmacologic agents used for the treatment of PHN. Pharmacy Practice, Nova Southeastern University College of Pharmacy-Davie Campus, Fort Lauderdale, Florida 33328-2018, USA. singh@nova.edu.
• McLean MJ, Morrell MJ, Willmore LJ, Privitera MD, Faught RE, Holmes GL, Magnus-Miller L, Bernstein P and Rose-Legatt A (1999). Safety and tolerability of gabapentin as adjunctive therapy in a large, multicenter study. Epilepsia 40:965-72. Summary: PURPOSE: To evaluate the tolerability and safety of gabapentin (GBP) as add-on therapy for seizure control. METHODS: Conducted in an outpatient setting and reflecting usual practice, this study compared tolerability of GBP dosages < or = 1,800 versus >1,800 mg/day, when these doses were required to achieve the most effective seizure control. Two analyses of adverse events are presented: tolerability and safety. In the tolerability analysis, each patient served as his or her own control to compare the occurrence of adverse events at GBP < or =1,800 versus >1,800 mg/day. The safety analysis required patients to receive at least one dose of GBP and have a follow-up contact. RESULTS: A total of 2,216 patients enrolled in this open-label, 16-week study and were evaluable for safety. Of these, 74.0% completed the 16-week study, and 281 met the tolerability criteria. Within these 281 patients, two mutually exclusive groups were compared (a) those reporting adverse events at only < or =1,800 mg/day [low dose); and [b) those reporting adverse events at only >1,800 mg/day (high dose). Three adverse events (asthenia, headache, and dizziness) were observed in a statistically significantly larger number of patients at only the low dose than in the group reporting these same adverse events at only the high dose, suggesting that patients who tolerated GBP at < or = 1,800 mg/day did not experience a significant increase in adverse events with dosages >1,800 mg/day. Overall, 10.6% of the 2,216 patients in the safety population prematurely withdrew because of adverse events, and 3.5% discontinued because of lack of efficacy. Safety and tolerability of GBP was rated as excellent or good for 78.5% of all patients. CONCLUSIONS: Gabapentin doses >1,800 mg/day were as well tolerated as doses < or =1,800 mg/day and were not associated with more adverse events. Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee 37212, USA.
• Beydoun A, Fakhoury T, Nasreddine W and Abou-Khalil B (1998). Conversion to high dose gabapentin monotherapy in patients with medically refractory partial epilepsy. Epilepsia 39:188-93. Summary: PURPOSE: To evaluate the safety and efficacy of high dose gabapentin (GBP) monotherapy (3,000-4,800 mg/day) in patients with medically refractory partial epilepsy. METHODS: GBP monotherapy at daily doses up to 4,800 mg was attempted in patients participating in the open-label phase of a double-blind, dose-controlled, GBP monotherapy trial. For those who achieved monotherapy, the types and severity of adverse events were assessed and the average seizure frequency per 28 days while maintained on the highest daily GBP dose was compared to the seizure frequency during the baseline phase of the double blind trial. Correlation analysis between GBP serum level, total daily dose, and percentage of seizure change from baseline was performed. RESULTS: A total of 45 patients participated in the open-label phase of the trial and 23 (51%) were converted successfully to GBP monotherapy. In those patients, the average daily gabapentin dose was 3,900 mg and the mean length of follow-up was 252 days. Compared to baseline, there was a mean reduction of 54%, 43%, and 14% for simple partial, complex partial and secondarily generalized seizures respectively, while maintained on high-dose GBP monotherapy. A significant linear correlation between daily GBP dosage (2,400-4,800 mg) and resultant mean serum levels was found (r = 0.51; p < 0.01). There was no significant correlation between seizure frequency and total daily GBP dose or with serum levels. High-dose GBP monotherapy was well tolerated; only one patient exited the trial because of adverse events. The most common adverse event was tiredness/sleepiness and was not dose-related. CONCLUSIONS: GBP monotherapy is well tolerated in daily doses of up to 4,800 mg and is effective in a subgroup of patients with medically refractory partial epilepsy. Department of Neurology, University of Michigan Medical Center, Ann Arbor 48109, USA.
I have heard from two people who take 9600 mg of Neurontin per day for neuropathic pain. I am NOT advocating this nor am I claiming that this is safe. I imagine that very few people can even tolerate this dosage. But FWIW, there's at least a couple of people who find some benefit from this high dosage and a couple of doctors who feel that it's appropriate to prescribe this level of Neurontin.
I should also mention that both people who are taking this much Neurontin have very bad cases of central pain and while the Neurontin does help some, it only provides a fractional level of relief.
i remember reading someplace that once you get a blood level established, which i think takes up to 2 weeks? the half life of neurontin is 5 hours and 25 minutes.
thats why the 6 hour doses do work bettter .
i do remember that a lot of the side effect did go away after a month, your body adjust to them, if you can tolerate it that long. it did for me. i had neurgenic bladder/urine retention and it also slowed down my bowel muscles.. i have cauda equine, so since those nerves are damanged the neurontin did affect them.
Originally posted by yonkersguy:
i remember reading someplace that once you get a blood level established, which i think takes up to 2 weeks? the half life of neurontin is 5 hours and 25 minutes.
thats why the 6 hour doses do work bettter .
i do remember that a lot of the side effect did go away after a month, your body adjust to them, if you can tolerate it that long. it did for me. i had neurgenic bladder/urine retention and it also slowed down my bowel muscles.. i have cauda equine, so since those nerves are damanged maybe? the neurontin did affect them.
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