gralise

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 ) 2.1 Postherpetic 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 2.2 Patients with Renal Impairment In patients with stable renal function, creatinine clearance (C Cr ) can be…

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 6.1 Clinical 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…

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 )

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.

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

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 ) 7.1 Phenytoin 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. 7.2 Carbamazepine 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. 7.3 Valproic 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. 7.4 Phenobarbital 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. 7.5 Naproxen 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. 7.6 Hydrocodone 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. 7.7 Morphine 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. 7.8 Cimetidine 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 not evaluated. This decrease is not expected to be clinically significant. 7.9 Oral Contraceptives Gabapentin immediate release (400 mg three times daily) had no effect on the pharmacokinetics of norethindrone (2.5 mg) or ethinyl estradiol (50 mcg) administered as a single tablet, except that the C max of norethindrone was increased by 13%. This interaction is not considered to be clinically significant. 7.10 Antacid (containing aluminum hydroxide and magnesium hydroxide) 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 immediate release was taken 2 hours after the antacid. It is recommended that GRALISE be taken at least 2 hours following the antacid (containing aluminum hydroxide and magnesium hydroxide) administration. 7.11 Probenecid Gabapentin immediate release pharmacokinetic parameters were comparable with and without probenecid, indicating that gabapentin does not undergo renal tubular secretion by the pathway that is blocked by probenecid. 7.12 Drug/Laboratory Test Interactions False positive readings were reported with the Ames-N-Multistix SG® dipstick test for urine protein when gabapentin was added to other antiepileptic drugs; therefore, the more specific sulfosalicylic acid precipitation procedure is recommended to determine the presence of urine protein.