Gralise once-daily (gabapentin) tablets

Mechanism of Delivery

GRALISE is absorbed gradually to manage PHN throughout the night and day

GRALISE is a unique formulation that delivers a gradual release of gabapentin over time.

The GRALISE Mechanism of Delivery

When taken with an evening meal, the unique technology of GRALISE allows for once-daily dosing.12

2 hours post-dose

Tablet expands and remains in the stomach to gradually release gabapentin to the upper gastrointestinal tract, the optimal site of absorption.134

8-10 hours post-dose

A gradual release of gabapentin from the stomach to the upper small intestine occurs over 8 to 10 hours.1

~15 hours post-dose

The GRALISE tablet completely dissolves approximately 15 hours after dosing.4

PHARMACOKINETIC DATA DO NOT PREDICT EFFICACY OR SAFETY
Do not use GRALISE interchangeably with other gabapentin products because of differing pharmacokinetic profiles that affect frequency of administration.2
GRALISE should be taken with an evening meal. If it is taken on an empty stomach, the bioavailability will be substantially lower.2

Pharmacokinetics

GRALISE vs gabapentin immediate release

GRALISE reaches peak concentration at 8 hours when taken once daily with the evening meal.1

GRALISE plasma levels peak overnight1

PHARMACOKINETIC DATA DO NOT PREDICT EFFICACY OR SAFETY
When GRALISE (1800 mg once daily) and gabapentin immediate release (600 mg three times a day) were administered with high-fat evening meals (50% of calories from fat), GRALISE had a higher Cmax and lower AUC at steady state compared to gabapentin immediate release. Time to reach maximum plasma concentration (Tmax) for GRALISE is 8 hours, which is about 4 to 6 hours longer compared to gabapentin immediate release.2
Do not use GRALISE interchangeably with other gabapentin products because of differing pharmacokinetic profiles that affect frequency of administration.2
GRALISE should be taken with an evening meal. If it is taken on an empty stomach, the bioavailability will be substantially lower.2

QD=Once daily; TID=3x/day.

References:

  1. Argoff CE, Chen C, Cowles VE. Clinical development of a once-daily gastroretentive formulation of gabapentin for treatment of postherpetic neuralgia: an overview. Expert Opin Drug Deliv. 2012;9(9):1147-1160.
  2. GRALISE. Prescribing information. Almatica Pharma LLC; 2023.
  3. Sang CN, Sathyanarayana R, Sweeney M; DM-1796 Study Investigators. Gastroretentive gabapentin (G-GR) formulation reduces intensity of pain associated with postherpetic neuralgia (PHN). Clin J Pain. 2013;29(4):281-288.
  4. Gordi T, Hou E, Kasichayanula S, Berner B. Pharmacokinetics of gabapentin after a single day and at steady state following the administration of gastric-retentive-extended-release and immediate-release tablets: a randomized, open-label, multiple-dose, three-way crossover, exploratory study in healthy subjects. Clin Ther. 2008;30(5):909-916.
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Gabapentin is a controlled substance in several states. Contact local authorities for more information. Advise patients to take GRALISE only as prescribed.

Important Safety Information

Contraindications

GRALISE is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients.

Warnings and Precautions

The safety and efficacy of GRALISE in patients with epilepsy have not been studied.

Suicidal 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. 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.

Respiratory Depression

Gabapentin has been associated with serious, life-threatening, or fatal respiratory depression when co-administered with central nervous system (CNS) depressants, including opioids, or when there is an underlying respiratory impairment. When the decision is made to co-prescribe GRALISE with another CNS depressant, particularly an opioid, or to prescribe GRALISE to patients with underlying respiratory impairment, monitor patients for symptoms of respiratory depression and sedation, and consider initiating GRALISE at a low dose.

Withdrawal of Gabapentin

Gabapentin should be withdrawn gradually. If GRALISE is discontinued, this should be done gradually over a minimum of 1 week or longer (at the discretion of the prescriber).

Tumorigenic Potential

In standard preclinical in vivo lifetime carcinogenicity studies, an unexpectedly high incidence of pancreatic acinar adenocarcinomas was identified in male, but not female, rats. The clinical significance of this finding is unknown.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as Multiorgan Hypersensitivity, has been reported in patients taking antiepileptic drugs, including GRALISE. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. If such signs or symptoms are present, the patient should be evaluated immediately.

Adverse Reactions

In clinical trials, the most common adverse reactions were dizziness (10.9%) and somnolence (4.5%). Across all GRALISE clinical trials, the other most common adverse reactions (≥2%) were headache, peripheral edema, diarrhea, dry mouth, and nasopharyngitis. The types and incidence of adverse events were similar across age groups except for peripheral edema, which tended to increase in incidence with age.

Drug Interactions

An increase in gabapentin AUC values has been reported when administered with hydrocodone or morphine.

It is recommended that GRALISE be taken at least 2 hours following antacid administration.

Use in Specific Populations

Pediatric Use

The safety and effectiveness of GRALISE in the management of postherpetic neuralgia in patients less than 18 years of age have not been studied.

Geriatric 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.

Hepatic Impairment

Because gabapentin is not metabolized, studies have not been conducted in patients with hepatic impairment.

Renal Impairment

Dosage adjustment of GRALISE is necessary in patients with impaired renal function. GRALISE should not be administered in patients with creatinine clearance <30 mL/min or in patients undergoing hemodialysis. Reductions in GRALISE dose should be made in patients with age-related compromised renal function.

Overdosage

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 CNS depressants.

Indications and Usage

GRALISE® (gabapentin) is indicated for the management of postherpetic neuralgia (PHN). GRALISE is not interchangeable with other gabapentin products because of differing pharmacokinetic profiles that affect the frequency of administration.

Please see the full Prescribing Information, including Medication Guide.