Gralise gabapentin 750 mg Tablet, Film Coated, 60-count
Other active recalls for Gabapentin (different manufacturers) — 6 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Gabapentinoids class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Gabapentin capsules, tablets, and oral solution are used along with other medications to help control certain types of seizures in people who have epilepsy. Gabapentin capsules, tablets, and oral solution are also used to relieve the pain of postherpetic neuralgia (PHN; the burning, stabbing pain or aches that may last for months or years after an attack of shingles). Gabapentin extended-release tablets (Horizant) are used to treat restless legs syndrome (RLS; a condition that causes discomfort in the legs and a strong urge to move the legs, especially at night and when sitting or lying down)....
Read the full MedlinePlus article ↗- Gabapentin is mainly used for two things: managing nerve pain that lingers after a shingles infection (called postherpetic neuralgia) in adults, and helping control partial onset s...
- This is a really important question. Taking gabapentin together with opioids like morphine, hydrocodone, or oxycodone significantly raises the risk of serious breathing problems —...
- Can I take gabapentin with my opioid pain medication?
- The most common ones — especially in the first few weeks — are dizziness, drowsiness, and sometimes loss of balance or coordination. Swelling in the feet or hands is also fairly co...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Gabapentin — tap one for details:
Gabapentin may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII D9C330MD8B
Copovidone is a synthetic polymer made by combining two types of plastic-like molecules. It acts as a binder and film-former to help hold tablet ingredients together and improve how the medicine dissolves in your body.
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Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
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Polyethylene glycol 7000000 is a synthetic polymer used as a binder and filler in medications. It helps hold tablet ingredients together and can improve how the medicine dissolves in your body.
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UNII 532B59J990
Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.
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A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
9 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $15.186 | $911.14 / 60 tablets |
| Medicaid paysCMS SDUD · 12 mo | $15.34 | $920.62 / 60 tablets |
| Medicare drug plans payPart D · Q2 2026 | $14.66 | $879.60 / 60 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Gralise 750 mgthis 52427-0850-60 | Almatica | 60 tablets | $15.186 | AB2 | Availability likely | — |
| gabapentin 750 mg 68382-0356-01 | Zydus | 100 tablets | — | AB2 | FDA listed | — |
| gabapentin 750 mg 70771-1917-01 | Zydus | 100 tablets | — | AB2 | FDA listed | — |
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⏳ Availability & generic status
FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 52427-0850-60 You're viewing this | 60 TABLET, FILM COATED in 1 BOTTLE (52427-850-60) | 2023-04-20 | Active |
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE GRALISE is indicated for the management of postherpetic neuralgia. GRALISE is not substitutable with other gabapentin products because of differing pharmacokinetic profiles that affect the frequency of administration. GRALISE is indicated for the management of Postherpetic Neuralgia (PHN).
Important Limitation: GRALISE is not substitutable with other gabapentin products because of differing pharmacokinetic profiles that affect the frequency of administration (See Warnings and Precautions )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION GRALISE should be titrated to an 1,800 mg dose taken orally, once-daily, with the evening meal. GRALISE tablets should be swallowed whole. Do not crush, split, or chew the tablets.
( 2.1 ) If GRALISE dose is reduced, discontinued, or substituted with an alternative medication, this should be done gradually over a minimum of 1 week or longer (at the discretion of the prescriber). ( 2.1 ) Renal impairment: Dose should be adjusted in patients with reduced renal function. GRALISE should not be used in patients with CrCl less than 30 or in patients on hemodialysis.
( 2.2 )
2.1Postherpetic Neuralgia Do not use GRALISE as a substitute for other gabapentin products. Titrate GRALISE to an 1,800 mg dose taken orally once daily with the evening meal. GRALISE tablets should be swallowed whole.
Do not split, crush, or chew the tablets. If GRALISE dosing is reduced, discontinued, or substituted with an alternative medication, this should be done gradually over a minimum of one week or longer (at the discretion of the prescriber). In adults with postherpetic neuralgia, GRALISE therapy should be initiated and titrated as follows: Table 1: GRALISE Recommended Titration Schedule Day 1 Day 2 Days 3-6 Days 7-10 Days 11-14 Day 15 Daily Dose 300 mg 600 mg 900 mg 1,200 mg 1,500 mg 1,800 mg
2.2Patients with Renal Impairment In patients with stable renal function, creatinine clearance (C Cr ) can be reasonably well estimated using the equation of Cockcroft and Gault: For females C Cr =(0.85)(140-age)(weight)/[(72)(S Cr )] For males C Cr =(140-age)(weight)/[(72)(S Cr )] where age is in years, weight is in kilograms and S Cr is serum creatinine in mg/dL. The dose of GRALISE should be adjusted in patients with reduced renal function, according to Table 2. Patients with reduced renal function must initiate GRALISE at a daily dose of 300 mg.
GRALISE should be titrated following the schedule outlined in Table 1. Daily dosing in patients with reduced renal function must be individualized based on tolerability and desired clinical benefit. Table 2: GRALISE Dosage Based on Renal Function Once-daily dosing Creatinine Clearance (mL/min) GRALISE Dose (once daily with evening meal) ≥ 60 1,800 mg 30 - 60 600 mg to 1,800 mg < 30 GRALISE should not be administered patients receiving hemodialysis GRALISE should not be administered
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Tablets: 300 mg, white, oval, debossed with “SLV” on one side and “300” on the other side. 450 mg, red, oval, debossed with “ALM” on one side and “450” on the other side. 600 mg, beige, oval, debossed with “SLV” on one side and “600” on the other side.
750 mg, yellow, oval, debossed with “ALM” on one side and “750” on the other side. 900 mg, pink, oval, debossed with “ALM” on one side and “900” on the other side. Tablets: 300 mg, 450 mg, 600 mg, 750 mg, and 900 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS GRALISE is contraindicated in patients with demonstrated hypersensitivity to the drug or its ingredients. GRALISE is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS GRALISE is not substitutable with other gabapentin products because of differing pharmacokinetic profiles that affect the frequency of administration. The safety and effectiveness of GRALISE in patients with epilepsy has not been studied. GRALISE is not substitutable with other gabapentin products Antiepileptic drugs, including gabapentin, the active ingredient in GRALISE, increase the risk of suicidal thoughts or behavior ( 5.1 ) Abrupt or rapid discontinuation may increase the risk for seizures.
Withdrawal symptoms or suicidal behavior and ideation have been observed after discontinuation. Taper GRALISE gradually over a minimum of 1 week. ( 5.2 ) Respiratory depression may occur with GRALISE when used with concomitant CNS depressants or in the setting of underlying respiratory impairment.
Monitor patients and adjust dosage as appropriate. ( 5.3 )
5.1Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including gabapentin, the active ingredient in GRALISE, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Suicidal behavior and ideation have also been reported in patients after discontinuation of gabapentin [see Warnings and Precautions ( 5.3 )] . Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated.
There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide. The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed.
Table 3 shows absolute and relative risk by indication for all evaluated AEDs. Table 3: Risk by Indication for Antiepileptic Drugs (including gabapentin, the active ingredient in GRALISE) in the Pooled Analysis Indication Placebo Patients with Events Per 1,000 Patients Drug Patients with Events Per 1,000 Patients Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients Risk Difference: Additional Drug Patients with Events Per 1,000 Patients Epilepsy 1.0 3.4 3.5
2.4Psychiatric 5.7 8.5 1.5
2.9Other 1.0 1.8 1.9
0.9Total 2.4 4.3 1.8
1.9The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications. Anyone considering prescribing GRALISE must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which p…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are described elsewhere in the labeling: Suicidal Behavior and Ideation [see Warnings and Precautions ( 5.1 )] Increased Risk of Adverse Reactions with Abrupt or Rapid Discontinuation [see Warnings and Precautions ( 5.2 )] Respiratory Depression [see Warnings and Precautions ( 5.3 )] Tumorigenic Potential [see Warnings and Precautions ( 5.4 )] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity [see Warnings and Precautions ( 5.5 )] Laboratory Tests [see Warnings and Precautions ( 5.6 )] The most common adverse reaction (greater than or equal to 5% and twice placebo) is dizziness.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Almatica Pharma LLC at 1-877-447-7979 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 359 patients with neuropathic pain associated with postherpetic neuralgia have received GRALISE at doses up to 1,800 mg daily during placebo-controlled clinical studies. In clinical trials in patients with postherpetic neuralgia, 9.7% of the 359 patients treated with GRALISE and 6.9% of 364 patients treated with placebo discontinued prematurely due to adverse reactions.
In the GRALISE treatment group, the most common reason for discontinuation due to adverse reactions was dizziness. Of GRALISE-treated patients who experienced adverse reactions in clinical studies, the majority of those adverse reactions were either "mild" or "moderate". Table 4 lists all adverse reactions, regardless of causality, occurring in at least 1% of patients with neuropathic pain associated with postherpetic neuralgia in the GRALISE group for which the incidence was greater than in the placebo group.
Table 4: Treatment-Emergent Adverse Reaction Incidence in Controlled Trials in Neuropathic Pain Associated with Postherpetic Neuralgia (Events in at Least 1% of all GRALISE-Treated Patients and More Frequent Than in the Placebo Group) Body System - Preferred Term GRALISE N = 359 % Placebo N = 364 % Ear and Labyrinth Disorders Vertigo 1.4
0.5Gastrointestinal Disorders Diarrhea 3.3
2.7Dry mouth 2.8
1.4Constipation 1.4
0.3Dyspepsia 1.4
0.8General Disorders Peripheral edema 3.9
0.3Pain 1.1
0.5Infections and Infestations Nasopharyngitis 2.5
2.2Urinary tract infection 1.7
0.5Investigations Weight increased 1.9
0.5Musculoskeletal and Connective Tissue Disorders Pain in extremity 1.9
0.5Back pain 1.7
1.1Nervous System Disorders Dizziness 10.9
2.2Somnolence 4.5
2.7Headache 4.2
4.1Lethargy 1.1
0.3In addition to the adverse reactions reported in Table 4 above, the following adverse reactions with an uncertain relationship to GRALISE were reported during the clinical development for the treatment of postherpetic neuralgia. Events in more than 1% of patients but equally or more frequently in the GRALISE-treated patients than in the placebo group included blood pressure increase, confusional state, gastroenteritis viral, herpes zoster, hypertension, joint swelling, memory impairment, nausea, pneumonia, pyrexia, rash, seasonal allergy, and upper respiratory infection.
6.2Postmarketing and Other Experience with other Formulations of Gabapentin In addition to the adverse experiences reported during clinical testing of gabapentin, the following adverse experiences have been reported in patients receiving other formulations of marketed gabapentin. These adverse experiences have not been listed above and data are insufficient to support an estimate of their incidence or to establish causation. The listing is alphabetized: angioedema, blood glucose fluctuation, breast enlargement, bullous pemphigoid, elevated creatine kinase, elevated liver function tests…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS In vitro studies were conducted to investigate the potential of gabapentin to inhibit the major cytochrome P450 enzymes (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) that mediate drug and xenobiotic metabolism using isoform selective marker substrates and human liver microsomal preparations. Only at the highest concentration tested (171 mcg/mL; 1mM) was a slight degree of inhibition (14% to 30%) of isoform CYP2A6 observed. No inhibition of any of the other isoforms tested was observed at gabapentin concentrations up to 171 mcg/mL (approximately 15 times the C max at 3,600 mg/day).
Gabapentin is not appreciably metabolized nor does it interfere with the metabolism of commonly coadministered antiepileptic drugs. The drug interaction data described in this section were obtained from studies involving healthy adults and adult patients with epilepsy. An increase in gabapentin AUC values have been reported when administered with hydrocodone.
( 7.6 ) An increase in gabapentin AUC values have been reported when administered with morphine. ( 7.7 ) An antacid containing aluminum hydroxide and magnesium hydroxide reduced the bioavailability of gabapentin immediate release by about approximately 20%, but by only 5% when gabapentin was taken 2 hours after antacids. It is recommended that GRALISE be taken at least 2 hours following antacid administration.
( 7.10 )
7.1Phenytoin In a single (400 mg) and multiple dose (400 mg three times daily) study of gabapentin immediate release in epileptic patients (N=8) maintained on phenytoin monotherapy for at least 2 months, gabapentin had no effect on the steady-state trough plasma concentrations of phenytoin and phenytoin had no effect on gabapentin pharmacokinetics.
7.2Carbamazepine Steady-state trough plasma carbamazepine and carbamazepine 10, 11 epoxide concentrations were not affected by concomitant gabapentin immediate release (400 mg three times daily; N=12) administration. Likewise, gabapentin pharmacokinetics were unaltered by carbamazepine administration.
7.3Valproic Acid The mean steady-state trough serum valproic acid concentrations prior to and during concomitant gabapentin immediate release administration (400 mg three times daily; N=17) were not different and neither were gabapentin pharmacokinetic parameters affected by valproic acid.
7.4Phenobarbital Estimates of steady-state pharmacokinetic parameters for phenobarbital or gabapentin immediate release (300 mg three times daily; N=12) are identical whether the drugs are administered alone or together.
7.5Naproxen Coadministration of single doses of naproxen (250 mg) and gabapentin immediate release (125 mg) to 18 volunteers increased gabapentin absorption by 12% to 15%. Gabapentin immediate release had no effect on naproxen pharmacokinetics. The doses are lower than the therapeutic doses for both drugs. The effect of coadministration of these drugs at therapeutic doses is not known.
7.6Hydrocodone Coadministration of gabapentin immediate release (125 mg and 500 mg) and hydrocodone (10 mg) reduced hydrocodone C max by 3% and 21%, respectively, and AUC by 4% and 22%, respectively. The mechanism of this interaction is unknown. Gabapentin AUC values were increased by 14%; the magnitude of the interaction at other doses is not known.
7.7Morphine When a single dose (60 mg) of controlled-release morphine capsule was administered 2 hours prior to a single dose (600 mg) of gabapentin immediate release in 12 volunteers, mean gabapentin AUC values increased by 44% compared to gabapentin immediate release administered without morphine. The pharmacokinetics of morphine were not affected by administration of gabapentin immediate release 2 hours after morphine. The magnitude of this interaction at other doses is not known.
7.8Cimetidine Cimetidine 300 mg decreased the apparent oral clearance of gabapentin by 14% and creatinine clearance by 10%. The effect of gabapentin immediate release on cimetidine was n…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Elderly: Reductions in GRALISE dose should be made in patients with age-related compromised renal function. ( 8.5 ) Renal impairment: Dosage adjustment is necessary for patients with impaired renal function. ( 8.7 )
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to gabapentin, including GRALISE, during pregnancy. Encourage women who are taking GRALISE during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling the toll free number 1-888-233-2334 or visiting https://www.aedpregnancyregistry.org/. Risk Summary Available data from published prospective and retrospective cohort studies, and case reports over decades of use with gabapentin during pregnancy have not identified a drug-associated risk of major birth defects.
The available data are insufficient to evaluate a drug-associated risk of miscarriage and other maternal or fetal outcomes. In nonclinical studies in mice, rats, and rabbits, gabapentin was developmentally toxic (increased fetal skeletal and visceral abnormalities, and increased embryofetal mortality) when administered to pregnant animals at doses similar to those used clinically (see Data) . Postmarketing data suggest that extended gabapentin use with opioids close to delivery mayincrease the risk of neonatal withdrawal versus opioids alone [see Clinical Considerations] .
Although there is at least one report of neonatal withdrawal syndrome in an infant exposed togabapentin alone during pregnancy, there are no comparative epidemiologic studies evaluatingthis association. Therefore, it is not known whether exposure to gabapentin alone late inpregnancy may cause withdrawal signs and symptoms. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Neonatal withdrawal syndrome has been reported in newborns exposed to gabapentin in utero foran extended period of time when also exposed to opioids close to delivery.
Neonatal withdrawal signs and symptoms reported have included tachypnea, vomiting, diarrhea, hypertonia, irritability, sneezing, poor feeding, hyperactivity, abnormal sleep pattern, and tremor. Reported signs and symptoms that may also be related to withdrawal include tongue thrusting, wandering eye movements while awake, back arching, and continuous extremity movements. Observe neonates exposed to GRALISE and opioids for signs and symptoms of neonatal withdrawal and manage accordingly.
Data Animal Data When pregnant mice received oral doses of gabapentin (1,000 or 3,000 mg/kg/day, approximately 3 to 8 times the maximum recommended dose of 1,800 mg on a mg/m 2 basis) during the period of organogenesis, embryofetal toxicity (increased incidences of skeletal variations) was observed. The no effect level was 500 mg/kg/day, representing approximately the maximum recommended human dose [MRHD] on a mg/m 2 basis. When rats were dosed prior to and during mating, and throughout gestation, pups from all dose groups (500, 1,000 and 2,000 mg/kg/day) were affected.
These doses are equivalent to approximately 3 to 11 times the MRHD on a mg/m 2 basis. There was an increased incidence of hydroureter and/or hydronephrosis in rats in a study of fertility and general reproductive performance at 2,000 mg/kg/day with no effect at 1,000 mg/kg/day, in a teratology study at 1,500 mg/kg/day with no effect at 300 mg/kg/day, and in a perinatal and postnatal study at all doses studied (500, 1,000 and 2,000 mg/kg/day). The doses at which the effects occurred are approximately 3 to 11 times the maximum rec…
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to gabapentin, including GRALISE, during pregnancy. Encourage women who are taking GRALISE during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling the toll free number 1-888-233-2334 or visiting https://www.aedpregnancyregistry.org/. Risk Summary Available data from published prospective and retrospective cohort studies, and case reports over decades of use with gabapentin during pregnancy have not identified a drug-associated risk of major birth defects.
The available data are insufficient to evaluate a drug-associated risk of miscarriage and other maternal or fetal outcomes. In nonclinical studies in mice, rats, and rabbits, gabapentin was developmentally toxic (increased fetal skeletal and visceral abnormalities, and increased embryofetal mortality) when administered to pregnant animals at doses similar to those used clinically (see Data) . Postmarketing data suggest that extended gabapentin use with opioids close to delivery mayincrease the risk of neonatal withdrawal versus opioids alone [see Clinical Considerations] .
Although there is at least one report of neonatal withdrawal syndrome in an infant exposed togabapentin alone during pregnancy, there are no comparative epidemiologic studies evaluatingthis association. Therefore, it is not known whether exposure to gabapentin alone late inpregnancy may cause withdrawal signs and symptoms. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Neonatal withdrawal syndrome has been reported in newborns exposed to gabapentin in utero foran extended period of time when also exposed to opioids close to delivery.
Neonatal withdrawal signs and symptoms reported have included tachypnea, vomiting, diarrhea, hypertonia, irritability, sneezing, poor feeding, hyperactivity, abnormal sleep pattern, and tremor. Reported signs and symptoms that may also be related to withdrawal include tongue thrusting, wandering eye movements while awake, back arching, and continuous extremity movements. Observe neonates exposed to GRALISE and opioids for signs and symptoms of neonatal withdrawal and manage accordingly.
Data Animal Data When pregnant mice received oral doses of gabapentin (1,000 or 3,000 mg/kg/day, approximately 3 to 8 times the maximum recommended dose of 1,800 mg on a mg/m 2 basis) during the period of organogenesis, embryofetal toxicity (increased incidences of skeletal variations) was observed. The no effect level was 500 mg/kg/day, representing approximately the maximum recommended human dose [MRHD] on a mg/m 2 basis. When rats were dosed prior to and during mating, and throughout gestation, pups from all dose groups (500, 1,000 and 2,000 mg/kg/day) were affected.
These doses are equivalent to approximately 3 to 11 times the MRHD on a mg/m 2 basis. There was an increased incidence of hydroureter and/or hydronephrosis in rats in a study of fertility and general reproductive performance at 2,000 mg/kg/day with no effect at 1,000 mg/kg/day, in a teratology study at 1,500 mg/kg/day with no effect at 300 mg/kg/day, and in a perinatal and postnatal study at all doses studied (500, 1,000 and 2,000 mg/kg/day). The doses at which the effects occurred are approximately 3 to 11 times the maximum recommended dose of 1,800 mg on a mg/m 2 basis; the no-effect doses were approximately 5 times (Fertility and General Reproductive Performance study) and approximately equal to (Teratogenicity study) the MRHD on a mg/m 2 basis.
Other than hydrourete…
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of GRALISE in the management of postherpetic neuralgia in patients less than 18 years of age has not been studied.
🧓 Geriatric Use ▾
8.5Geriatric Use The total number of patients treated with GRALISE in controlled clinical trials in patients with postherpetic neuralgia was 359, of which 63% were 65 years of age or older. The types and incidence of adverse events were similar across age groups except for peripheral edema, which tended to increase in incidence with age. GRALISE is known to be substantially excreted by the kidney.
Reductions in GRALISE dose should be made in patients with age-related compromised renal function [see Dosage and Administration ( 2.2 )] .
🆘 Overdosage ▾
10 OVERDOSAGE Signs of acute toxicity in animals included ataxia, labored breathing, ptosis, sedation, hypoactivity, or excitation. Acute oral overdoses of gabapentin have been reported. Symptoms include double-vision, tremor, slurred speech, drowsiness, altered mental status, dizziness, lethargy, and diarrhea.
Fatal respiratory depression has been reported with gabapentin overdose, alone and in combination with other central nervous system (CNS) depressants. Gabapentin can be removed by hemodialysis. Hemodialysis has been performed in overdose cases reported, and it may be indicated by the patient’s clinical state or in patients with significant renal impairment.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action The mechanism of action by which gabapentin exerts its analgesic action is unknown but in animal models of analgesia, gabapentin prevents allodynia (pain-related behavior in response to a normally innocuous stimulus) and hyperalgesia (exaggerated response to painful stimuli). Gabapentin prevents pain-related responses in several models of neuropathic pain in rats and mice (e.g., spinal nerve ligation models, spinal cord injury model, acute herpes zoster infection model). Gabapentin also decreases pain-related responses after peripheral inflammation (carrageenan footpad test, late phase of formulin test), but does not alter immediate pain-related behaviors (rat tail flick test, formalin footpad acute phase).
The relevance of these models to human pain is not known. Gabapentin is structurally related to the neurotransmitter GABA (gamma-aminobutyric acid), but it does not modify GABA A or GABA B radioligand binding, it is not converted metabolically into GABA or a GABA agonist, and it is not an inhibitor of GABA uptake or degradation. In radioligand binding assays at concentrations up to 100 μM, gabapentin did not exhibit affinity for a number of other receptor sites, including benzodiazepine, glutamate, N-methyl-D-aspartate (NMDA), quisqualate, kainate, strychnine-insensitive or strychnine-sensitive glycine; alpha 1, alpha 2, or beta adrenergic; adenosine A1 or A2; cholinergic, muscarinic, or nicotinic; dopamine D1 or D2; histamine H1; serotonin S1 or S2; opiate mu, delta, or kappa; cannabinoid 1; voltage-sensitive calcium channel sites labeled with nitrendipine or diltiazem; or at voltage-sensitive sodium channel sites labeled with batrachotoxinin A20-alpha-benzoate.
Gabapentin did not alter the cellular uptake of dopamine, noradrenaline, or serotonin. In vitro studies with radiolabeled gabapentin have revealed a gabapentin binding site in areas of rat brain including neocortex and hippocampus. A high-affinity binding protein in animal brain tissue has been identified as an auxiliary subunit of voltage-activated calcium channels.
However, functional correlates of gabapentin binding, if any, remain to be elucidated. It is hypothesized that gabapentin antagonizes thrombospondin binding to α2δ-1 as a receptor involved in excitatory synapse formation and suggested that gabapentin may function therapeutically by blocking new synapse formation.
12.2Pharmacodynamics No pharmacodynamic studies have been conducted with GRALISE.
12.3Pharmacokinetics Absorption Gabapentin is absorbed from the proximal small bowel by a saturable L-amino transport system. Gabapentin bioavailability is not dose proportional; as the dose is increased, bioavailability decreases. When GRALISE (1,800 mg once daily) and gabapentin immediate release (600 mg three times a day) were administered with high fat meals (50% of calories from fat), GRALISE has a higher C max and lower AUC at steady state compared to gabapentin immediate release (Table 5).
Time to reach maximum plasma concentration (T max ) for GRALISE is 8 hours, which is about 4-6 hours longer compared to gabapentin immediate release. Table 5: Mean ± SD Steady-State Pharmacokinetics for GRALISE and Gabapentin Immediate Release in Healthy Subjects under high-fat high calorie fed state (Day 5, n = 21) Pharmacokinetic Parameter (Mean ± SD) GRALISE 1,800 mg QD (3 x 600 mg) Gabapentin Immediate Release 600 mg TID $ Tmax is presented as median (range); * relative to most recent dose AUC0-24 (μg.hr/mL) 132.8 ± 34.7 141.3 ±
29.8C max (μg/mL) 9.59 ± 2.33 8.54 ±
1.72C min (μg/mL) 1.84 ± 0.65 2.6 ±
0.78T max (hr) $ 8 (3-12) 2 (1-5)* The single dose pharmacokinetic parameters of 900 mg strength under high fat-high calorie fed state and low fat-low calorie fed state are presented shown in Table 6. Table 6: Mean ± SD Single-Dose Pharmacokinetic parameters for GRALISE 900 mg strength in Healthy Subjects (n = 27) $ Tmax is presented as median (range) Pharmacokinetic…
🧬 Mechanism of Action ▾
12.1Mechanism of Action The mechanism of action by which gabapentin exerts its analgesic action is unknown but in animal models of analgesia, gabapentin prevents allodynia (pain-related behavior in response to a normally innocuous stimulus) and hyperalgesia (exaggerated response to painful stimuli). Gabapentin prevents pain-related responses in several models of neuropathic pain in rats and mice (e.g., spinal nerve ligation models, spinal cord injury model, acute herpes zoster infection model). Gabapentin also decreases pain-related responses after peripheral inflammation (carrageenan footpad test, late phase of formulin test), but does not alter immediate pain-related behaviors (rat tail flick test, formalin footpad acute phase).
The relevance of these models to human pain is not known. Gabapentin is structurally related to the neurotransmitter GABA (gamma-aminobutyric acid), but it does not modify GABA A or GABA B radioligand binding, it is not converted metabolically into GABA or a GABA agonist, and it is not an inhibitor of GABA uptake or degradation. In radioligand binding assays at concentrations up to 100 μM, gabapentin did not exhibit affinity for a number of other receptor sites, including benzodiazepine, glutamate, N-methyl-D-aspartate (NMDA), quisqualate, kainate, strychnine-insensitive or strychnine-sensitive glycine; alpha 1, alpha 2, or beta adrenergic; adenosine A1 or A2; cholinergic, muscarinic, or nicotinic; dopamine D1 or D2; histamine H1; serotonin S1 or S2; opiate mu, delta, or kappa; cannabinoid 1; voltage-sensitive calcium channel sites labeled with nitrendipine or diltiazem; or at voltage-sensitive sodium channel sites labeled with batrachotoxinin A20-alpha-benzoate.
Gabapentin did not alter the cellular uptake of dopamine, noradrenaline, or serotonin. In vitro studies with radiolabeled gabapentin have revealed a gabapentin binding site in areas of rat brain including neocortex and hippocampus. A high-affinity binding protein in animal brain tissue has been identified as an auxiliary subunit of voltage-activated calcium channels.
However, functional correlates of gabapentin binding, if any, remain to be elucidated. It is hypothesized that gabapentin antagonizes thrombospondin binding to α2δ-1 as a receptor involved in excitatory synapse formation and suggested that gabapentin may function therapeutically by blocking new synapse formation.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING GRALISE (gabapentin) Tablets are supplied as follows: • 300 mg tablets: GRALISE 300 mg tablets are white, oval, debossed with “SLV” on one side and “300” on the other side. NDC 52427-803-90 (Bottle of 90) • 450 mg tablets: GRALISE 450 mg tablets are red, oval, debossed with “ALM” on one side and “450” on the other side. NDC 52427-804-60 (Bottle of 60) • 600 mg tablets: GRALISE 600 mg tablets are beige, oval, debossed with “SLV” on one side and “600” on the other side.
NDC 52427-806-90 (Bottle of 90) • 750 mg tablets: GRALISE 750 mg tablets are yellow, oval, debossed with “ALM” on one side and “750” on the other side. NDC 52427-850-60 (Bottle of 60) • 900 mg tablets: GRALISE 900 mg tablets are pink, oval, debossed with “ALM” on one side and “900” on NDC 52427-890-60 (Bottle of 60) Storage Store at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted to 15ºC to 30ºC (59ºF to 86ºF) [see USP Controlled Room Temperature]. Keep out of reach of children.
📋 Description ▾
11 DESCRIPTION GRALISE contains gabapentin, a gamma-aminobutyric acid (GABA) analogue, as the active pharmaceutical ingredient. Gabapentin's chemical name is 1-(aminomethyl)cyclohexaneacetic acid; with a molecular formula of C 9 H 17 NO 2 and a molecular weight of 171.24 g/mol. Gabapentin chemical structural formula is: Gabapentin is a white to off-white crystalline solid with a pKa1 of 3.7 and a pKa2 of 10.7.
It is freely soluble in water and acidic and basic solutions. The log of the partition coefficient (n-octanol/ 0.05M phosphate buffer) at pH 7.4 is -1.25. GRALISE is intended for oral administration and is supplied as tablets containing 300 mg, 450 mg, 600 mg, 750 mg, or 900 mg of gabapentin USP.
Each 300 mg tablet contains the inactive ingredients Copovidone NF, Hypromellose USP, Magnesium Stearate NF, Microcrystalline Cellulose NF, Polyethylene Oxide NF, and white film coating (Polyvinyl Alcohol USP, Talc USP, Titanium Oxide USP, Polyethylene Glycol 3350 USP, and Lecithin NF (soya)). Each 450 mg tablet contains the inactive ingredients Copovidone NF, Hypromellose USP, Magnesium Stearate NF, Polyethylene Oxide NF, and red film coating (Polyethylene glycol 3350 USP, Polyvinyl Alcohol USP, Talc USP, Titanium Oxide USP, and Iron Oxide Red NF).
Each 600 mg tablet contains the inactive ingredients Copovidone NF, Hypromellose USP, Magnesium Stearate NF, Polyethylene Oxide NF, and beige film coating (Polyethylene Glycol 3350 USP, Polyvinyl Alcohol USP, Talc USP, Titanium Oxide USP, Iron Oxide Yellow NF, and Iron Oxide Red NF). Each 750 mg tablet contains the inactive ingredients Copovidone NF, Hypromellose USP, Magnesium Stearate NF, Polyethylene Oxide NF, and yellow film coating (Polyethylene Glycol 3350 USP, Polyvinyl Alcohol USP, Talc USP, Titanium oxide USP, and Iron Oxide Yellow NF).
Each 900 mg tablet contains the inactive ingredients Copovidone NF, Hypromellose USP, Magnesium Stearate NF, Polyethylene Oxide NF, and pink film coating (Polyethylene Glycol 3350 USP, Polyvinyl Alcohol USP, Talc USP, Titanium oxide USP, and Iron Oxide Red NF). structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise patients of the availability of a Medication Guide , and instruct them to read the Medication Guide prior to taking GRALISE. Advise patients that GRALISE is not substitutable with other formulations of gabapentin. Advise patients to take GRALISE only as prescribed.
GRALISE may cause dizziness, somnolence, and other signs and symptoms of CNS depression. Advise patients not to drive or operate other complex machinery until they have gained sufficient experience on GRALISE to gauge whether or not it adversely affects their mental and/or motor performance. Advise patients who require concomitant treatment with morphine to tell their prescriber if they develop signs of CNS depression such as somnolence.
If this occurs the dose of GRALISE or morphine should be reduced accordingly. Advise patients that if they miss a dose of GRALISE to take it with food as soon as they remember. If it is almost time for the next dose, just skip the missed dose and take the next dose at the regular time.
Do not take two doses at the same time. Advise patients that if they take too much GRALISE, to call their healthcare provider or poison control center, or go to the nearest emergency room right away. Suicidal Thoughts and Behavior Counsel patients, their caregivers, and families that AEDs, including gabapentin, the active ingredient in GRALISE, may increase the risk of suicidal thoughts and behavior and of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm.
Instruct patients, caregivers, and families to report behaviors of concern immediately to healthcare providers. Also inform patients who plan to or have discontinued GRALISE that suicidal thoughts and behavior can appear even after the drug is stopped [see Warnings and Precautions ( 5.1 )] . Respiratory Depression Inform patients about the risk of respiratory depression.
Include information that the risk is greatest for those using concomitant central nervous system (CNS) depressants (such as opioid analgesics) or in those with underlying respiratory impairment. Teach patients how to recognize respiratory depression and advise them to seek medical attention immediately if it occurs [see Warnings and Precautions ( 5.3 )] . Dosing and Administration GRALISE is not substitutable with other gabapentin products because of differing pharmacokinetic profiles that affect the frequency of administration.
The safety and effectiveness of GRALISE in patients with epilepsy has not been studied. Advise patients that GRALISE should be taken orally once daily with the evening meal. GRALISE tablets should be swallowed whole.
Do not split, crush, or chew the tablets [see Dosage and Administration ( 2.1 )] . Use in Pregnancy Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with GRALISE, and to notify their physician if they are breast feeding or intend to breast feed during therapy [ see Use in Specific Populations ( 8.1 ) and ( 8.2 )] . Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) PregnancyRegistry if they become pregnant.
This registry is collecting information about the safety ofantiepileptic drugs during pregnancy. To enroll, patients can call the toll-free number 1-888-233-2334 [see Use in Specific Populations ( 8.1 )] .
💬 Medication Guide ▾
MEDICATION GUIDE GRALISE ® (gra leez') (gabapentin) Tablets Read this Medication Guide before you start taking GRALISE and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.
If you have any questions about GRALISE, ask your healthcare provider or pharmacist. What is the most important information I should know about GRALISE? Do not stop taking GRALISE without first talking with your healthcare provider.
Stopping GRALISE suddenly can cause serious problems. Like other antiepileptic drugs, gabapentin, the active ingredient in GRALISE, may cause suicidal thoughts or actions in a very small number of people, about 1 in 500. This can happen while you take GRALISE or after stopping.
However, it is not known if GRALISE is safe and effective in people with seizure problems (epilepsy). Therefore, GRALISE should not be used in place of other gabapentin products. Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you: thoughts about suicide or dying attempts to commit suicide serious breathing problems new or worse depression new or worse anxiety feeling agitated or restless panic attacks trouble sleeping (insomnia) new or worse irritability acting aggressive, being angry, or violent acting on dangerous impulses an extreme increase in activity and talking (mania) other unusual changes in behavior or mood How can I watch for early symptoms of suicidal thoughts and actions?
Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you are worried about symptoms.
Serious breathing problems Serious breathing problems can occur when GRALISE is taken with other medicines that can cause severe sleepiness or decreased awareness, or when it is taken by someone who already has breathing problems. Watch for increased sleepiness or decreased breathing when starting GRALISE or when the dose is increased. Get help right away if breathing problems occur.
Do not stop taking GRALISE without first talking with your healthcare provider. Stopping GRALISE suddenly can cause serious problems. What is GRALISE?
GRALISE is a prescription medicine used in adults, 18 years and older, to treat: pain from damaged nerves (neuropathic pain) that follows healing of shingles (a painful rash that comes after a herpes zoster infection). It is not known if GRALISE is safe and effective in people with seizure problems (epilepsy). It is not known if GRALISE is safe and effective in children under 18 years of age with postherpetic pain.
GRALISE is not substitutable with other gabapentin products. Who should not take GRALISE? Do not take GRALISE if you are allergic to gabapentin or any of the ingredients in GRALISE.
See the end of this Medication Guide for a complete list of ingredients in GRALISE. What should I tell my healthcare provider before taking GRALISE? Before taking GRALISE, tell your healthcare provider if you: have or have had depression, mood problems or suicidal thoughts or behavior have breathing problems have seizures have kidney problems or get kidney dialysis are pregnant or plan to become pregnant.
It is not known if GRALISE can harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking GRALISE. You and your healthcare provider will decide if you should take GRALISE while you are pregnant.
If you become pregnant while taking GRALISE, talk to your healthcare provider about registering with the North American Antiepileptic Drug (NAAED) Pregnancy Registry. The purpose of this registry is to collect information about the safety of antiepileptic drugs, including gabapentin, the active ingredient in GRALISE, during pregnancy. You can enroll in this regi…