gabapentin 800 MG Oral Tablet
Generic Name: GABAPENTIN
Brand Name: GABAPENTIN
- Substance Name(s):
- GABAPENTIN
WARNINGS
Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including gabapentin, 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.
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 to 100 years) in the clinical trials analyzed.
Table 2 shows absolute and relative risk by indication for all evaluated AEDs.
TABLE 2 Risk by indication for antiepileptic drugs in the pooled analysis Indication Placebo Patients with Events Per 1000 Patients Drug Patients with Events Per 1000 Patients Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients Risk Difference: Additional Drug Patients with Events Per 1000 Patients Epilepsy 1.0 3.4 3.5 2.4 Psychiatric 5.7 8.5 1.5 2.9 Other 1.0 1.8 1.9 0.9 Total 2.4 4.3 1.8 1.9 The 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 gabapentin or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness.
Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior.
Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm.
Behaviors of concern should be reported immediately to healthcare providers.
Neuropsychiatric Adverse Events–Pediatric Patients 3 to 12 Years of Age Gabapentin use in pediatric patients with epilepsy 3 to 12 years of age is associated with the occurrence of central nervous system related adverse events.
The most significant of these can be classified into the following categories: 1) emotional lability (primarily behavioral problems), 2) hostility, including aggressive behaviors, 3) thought disorder, including concentration problems and change in school performance, and 4) hyperkinesia (primarily restlessness and hyperactivity).
Among the gabapentin-treated patients, most of the events were mild to moderate in intensity.
In controlled trials in pediatric patients 3 to 12 years of age, the incidence of these adverse events was: emotional lability 6% (gabapentin-treated patients) vs 1.3% (placebo-treated patients); hostility 5.2% vs 1.3%; hyperkinesia 4.7% vs 2.9%; and thought disorder 1.7% vs 0%.
One of these events, a report of hostility, was considered serious.
Discontinuation of gabapentin treatment occurred in 1.3% of patients reporting emotional lability and hyperkinesia and 0.9% of gabapentin-treated patients reporting hostility and thought disorder.
One placebo-treated patient (0.4%) withdrew due to emotional lability.
Withdrawal Precipitated Seizure, Status Epilepticus Antiepileptic drugs should not be abruptly discontinued because of the possibility of increasing seizure frequency.
In the placebo-controlled studies in patients > 12 years of age, the incidence of status epilepticus in patients receiving gabapentin was 0.6% (3 of 543) versus 0.5% in patients receiving placebo (2 of 378).
Among the 2074 patients > 12 years of age treated with gabapentin across all studies (controlled and uncontrolled) 31 (1.5%) had status epilepticus.
Of these, 14 patients had no prior history of status epilepticus either before treatment or while on other medications.
Because adequate historical data are not available, it is impossible to say whether or not treatment with gabapentin is associated with a higher or lower rate of status epilepticus than would be expected to occur in a similar population not treated with gabapentin.
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 (See PRECAUTIONS , Carcinogenesis, Mutagenesis, Impairment of Fertility).
The clinical significance of this finding is unknown.
Clinical experience during gabapentin’s premarketing development provides no direct means to assess its potential for inducing tumors in humans.
In clinical studies in adjunctive therapy in epilepsy comprising 2085 patient-years of exposure in patients > 12 years of age, new tumors were reported in 10 patients (2 breast, 3 brain, 2 lung, 1 adrenal, 1 non-Hodgkin’s lymphoma, 1 endometrial carcinoma in situ), and preexisting tumors worsened in 11 patients (9 brain, 1 breast, 1 prostate) during or up to 2 years following discontinuation of gabapentin.
Without knowledge of the background incidence and recurrence in a similar population not treated with gabapentin, it is impossible to know whether the incidence seen in this cohort is or is not affected by treatment.
Sudden and Unexplained Death in Patients With Epilepsy During the course of premarketing development of gabapentin 8 sudden and unexplained deaths were recorded among a cohort of 2203 patients treated (2103 patient-years of exposure).
Some of these could represent seizure-related deaths in which the seizure was not observed, e.g., at night.
This represents an incidence of 0.0038 deaths per patient-year.
Although this rate exceeds that expected in a healthy population matched for age and sex, it is within the range of estimates for the incidence of sudden unexplained deaths in patients with epilepsy not receiving gabapentin (ranging from 0.0005 for the general population of epileptics to 0.003 for a clinical trial population similar to that in the gabapentin program, to 0.005 for patients with refractory epilepsy).
Consequently, whether these figures are reassuring or raise further concern depends on comparability of the populations reported upon to the gabapentin cohort and the accuracy of the estimates provided.
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 gabapentin.
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.
Eosinophilia is often present.
Because this disorder is variable in its expression, other organ systems not noted here may be involved.
It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident.
If such signs or symptoms are present, the patient should be evaluated immediately.
Gabapentin should be discontinued if an alternative etiology for the signs or symptoms cannot be established.
DRUG INTERACTIONS
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; 1 mM) 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 Cmax at 3600 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.
OVERDOSAGE
A lethal dose of gabapentin was not identified in mice and rats receiving single oral doses as high as 8000 mg/kg.
Signs of acute toxicity in animals included ataxia, labored breathing, ptosis, sedation, hypoactivity, or excitation.
Acute oral overdoses of gabapentin up to 49 grams have been reported.
In these cases, double vision, slurred speech, drowsiness, lethargy and diarrhea were observed.
All patients recovered with supportive care.
Gabapentin can be removed by hemodialysis.
Although hemodialysis has not been performed in the few overdose cases reported, it may be indicated by the patient’s clinical state or in patients with significant renal impairment.
DESCRIPTION
Gabapentin tablets, USP are white colored film coated, modified capsule shaped biconvex tablets containing 600 mg and 800 mg of gabapentin, USP.
Each tablet for oral administration contains the following inactive ingredients: Mannitol, Hydroxypropyl Cellulose, Crospovidone, Talc, Magnesium Stearate and Aquarius® BP18114 Cool Vanilla.
Gabapentin is described as 1-(aminomethyl)cyclohexaneacetic acid with a molecular formula of C9H17NO2 and a molecular weight of 171.24.
The structural formula of gabapentin 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 both basic and acidic aqueous solutions.
The log of the partition coefficient (n-octanol/0.05M phosphate buffer) at pH 7.4 is -1.25.
This product(Gabapentin Tablets, USP 600 mg and 800 mg) meets the USP Dissolution Test 1.
gabapentin-structure
CLINICAL STUDIES
Clinical Studies
HOW SUPPLIED
Gabapentin Tablets, USP 600 mg: White colored film coated, Modified Capsule shaped, biconvex tablets de-bossed with ‘1’ on the left side of the bisect and ‘2’ on the right side of the bisect on one side and bisect on other; supplied in: 30 TABLET in a BOTTLE (0440-5562-30) 60 TABLET in a BOTTLE (0440-5562-60) 300 TABLET in a BOTTLE (0440-5562-81) 120 TABLET in a BOTTLE (0440-5562-91) 180 TABLET in a BOTTLE (0440-5562-92) 270 TABLET in a BOTTLE (0440-5562-94) 500 TABLET in a BOTTLE (0440-5562-05) 90 TABLET in a BOTTLE (0440-5562-90) Gabapentin Tablets, USP 800 mg: White colored film coated, Modified Capsule shaped, biconvex tablets de-bossed with ‘1’ on the left side of the bisect and ‘3’ on the right side of the bisect on one side and bisect on other; supplied in: 30 TABLET in a BOTTLE (0440-5563-30) 60 TABLET in a BOTTLE (0440-5563-60) 300 TABLET in a BOTTLE (0440-5563-81) 120 TABLET in a BOTTLE (0440-5563-91) 180 TABLET in a BOTTLE (0440-5563-92) 270 TABLET in a BOTTLE (0440-5563-94) 500 TABLET in a BOTTLE (0440-5563-05) 90 TABLET in a BOTTLE (0440-5563-90) Store at 20° to 25°C (68° to 77°F).
[See USP controlled room temperature].
PACKAGED BY: AIDAREX PHARMACEUTICALS LLC, CORONA CA, 92880 Rev: 08/2016.
GERIATRIC USE
Geriatric Use The total number of patients treated with gabapentin in controlled clinical trials in patients with postherpetic neuralgia was 336, of which 102 (30%) were 65 to 74 years of age, and 168 (50%) were 75 years of age and older.
There was a larger treatment effect in patients 75 years of age and older compared with younger patients who received the same dosage.
Since gabapentin is almost exclusively eliminated by renal excretion, the larger treatment effect observed in patients ≥75 years may be a consequence of increased gabapentin exposure for a given dose that results from an age-related decrease in renal function.
However, other factors cannot be excluded.
The types and incidence of adverse events were similar across age groups except for peripheral edema and ataxia, which tended to increase in incidence with age.
Clinical studies of gabapentin in epilepsy did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects.
Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function.
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients (see CLINICAL PHARMACOLOGY, ADVERSE REACTIONS, and DOSAGE AND ADMINISTRATION sections).
MECHANISM OF ACTION
Mechanism of Action The mechanism 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).
In particular, gabapentin prevents pain-related responses in several models of neuropathic pain in rats or mice (e.g., spinal nerve ligation models, streptozocin-induced diabetes model, spinal cord injury model, acute herpes zoster infection model).
Gabapentin also decreases pain-related responses after peripheral inflammation (carrageenan footpad test, late phase of formalin test).
Gabapentin did not alter immediate pain-related behaviors (rat tail flick test, formalin footpad acute phase, acetic acid abdominal constriction test, footpad heat irradiation test).
The relevance of these models to human pain is not known.
The mechanism by which gabapentin exerts its anticonvulsant action is unknown, but in animal test systems designed to detect anticonvulsant activity, gabapentin prevents seizures as do other marketed anticonvulsants.
Gabapentin exhibits antiseizure activity in mice and rats in both the maximal electroshock and pentylenetetrazole seizure models and other preclinical models (e.g., strains with genetic epilepsy, etc.).
The relevance of these models to human epilepsy is not known.
Gabapentin is structurally related to the neurotransmitter GABA (gamma-aminobutyric acid) but it does not modify GABAA or GABAB radioligand binding, it is not converted metabolically into GABA or a GABA agonist, and it is not an inhibitor of GABA uptake or degradation.
Gabapentin was tested in radioligand binding assays at concentrations up to 100 µM and did not exhibit affinity for a number of other common 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 A 20-alpha-benzoate.
Furthermore, 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.
INDICATIONS AND USAGE
INDICATIONS & USAGE Gabapentin Tablets, USP Read the Medication Guide before you start taking gabapentin 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.
What is the most important information I should know about gabapentin? Do not stop taking gabapentin without first talking to your healthcare provider.
Stopping gabapentin suddenly can cause serious problems.
Gabapentin can cause serious side effects including: 1.
Like other antiepileptic drugs, gabapentin may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.
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 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.
Do not stop taking gabapentin without first talking to a healthcare provider.
Stopping gabapentin suddenly can cause serious problems.
Stopping a seizure medicine suddenly in a patient who has epilepsy can cause seizures that will not stop (status epilepticus).
Suicidal thoughts or actions can be caused by things other than medicines.
If you have suicidal thoughts or actions, your healthcare provider may check for other causes.
2.
Changes in behavior and thinking – Using gabapentin in children 3 to 12 years of age can cause emotional changes, aggressive behavior, problems with concentration, restlessness, changes in school performance, and hyperactivity.
What is gabapentin? Gabapentin is a prescription medicine used to treat: Pain from damaged nerves (postherpetic pain) that follows healing of shingles (a painful rash that comes after a herpes zoster infection) in adults.
Partial seizures when taken together with other medicines in adults and children 3 years of age and older.
Who should not take gabapentin? Do not take gabapentin if you are allergic to gabapentin or any of the other ingredients in gabapentin.
See the end of this Medication Guide for a complete list of ingredients in gabapentin.
What should I tell my healthcare provider before taking gabapentin? Before taking gabapentin, tell your healthcare provider if you: have or have had kidney problems or are on hemodialysis have or have had depression, mood problems, or suicidal thoughts or behavior are pregnant or plan to become pregnant.
It is not known if gabapentin can harm your unborn baby.
Tell your healthcare provider right away if you become pregnant while taking gabapentin.
You and your healthcare provider will decide if you should take gabapentin while you are pregnant.
If you become pregnant while taking gabapentin, 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 during pregnancy.
You can enroll in this registry by calling 1-888-233-2334.
are breastfeeding or plan to breastfeed.
Gabapentin can pass into breast milk.
You and your healthcare provider should decide how you will feed your baby while you take gabapentin.
Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.
Taking gabapentin with certain other medicines can cause side effects or affect how well they work.
Do not start or stop other medicines without talking to your healthcare provider.
Know the medicines you take.
Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.
How should I take gabapentin? Take gabapentin exactly as prescribed.
Your healthcare provider will tell you how much gabapentin to take.
Do not change your dose of gabapentin without talking to your healthcare provider.
If you break a tablet in half the unused half of the tablet should be taken at your next scheduled dose.
Half tablets not used within several days of breaking should be thrown away.
Gabapentin can be taken with or without food.
If you take an antacid containing aluminum and magnesium, such as Maalox®, Mylanta®, Gelusil®, Gaviscon®, or Di-Gel®, you should wait at least 2 hours before taking your next dose of gabapentin.
If you take too much gabapentin, call your healthcare provider or your local Poison Control Center right away.
What should I avoid while taking gabapentin? Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking gabapentin without first talking with your healthcare provider.
Taking gabapentin with alcohol or drugs that cause sleepiness or dizziness may make your sleepiness or dizziness worse.
Do not drive, operate heavy machinery, or do other dangerous activities until you know how gabapentin affects you.
Gabapentin can slow your thinking and motor skills.
What are the possible side effects of gabapentin? See “What is the most important information I should know about gabapentin?” The most common side effects of gabapentin include: dizziness lack of coordination viral infection feeling drowsy feeling tired fever jerky movements difficulty with speaking temporary loss of memory (amnesia) tremor difficulty with coordination double vision unusual eye movement Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of gabapentin.
For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects.
You may report side effects to FDA at 1-800-FDA-1088.
How should I store gabapentin? Store gabapentin tablets at 20° to 25°C (68° to 77°F).
[See USP controlled room temperature].
Keep gabapentin and all medicines out of the reach of children.
General information about the safe and effective use of gabapentin Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide.
Do not use gabapentin for a condition for which it was not prescribed.
Do not give gabapentin to other people, even if they have the same symptoms that you have.
It may harm them.
This Medication Guide summarizes the most important information about gabapentin.
If you would like more information, talk with your healthcare provider.
You can ask your healthcare provider or pharmacist for information about gabapentin that was written for healthcare professionals.
For more information about gabapentin tablets, or to report side effects regarding gabapentin tablets, please call Exelan Pharmaceuticals Inc.
at 1-855-295-7455.
What are the ingredients in gabapentin Tablets? Active ingredient: Gabapentin, USP Inactive ingredients: Mannitol, Hydroxypropyl Cellulose, Crospovidone, Talc, Magnesium Stearate and Aquarius® BP18114 Cool Vanilla.
Postherpetic Neuralgia Gabapentin tablets USP are indicated for the management of postherpetic neuralgia in adults.
Epilepsy Gabapentin tablets USP are indicated as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in patients over 12 years of age with epilepsy.
Gabapentin tablets USP are also indicated as adjunctive therapy in the treatment of partial seizures in pediatric patients age 3 to 12 years.
PEDIATRIC USE
Pediatric Use Safety and effectiveness of gabapentin in the management of postherpetic neuralgia in pediatric patients have not been established.
Effectiveness as adjunctive therapy in the treatment of partial seizures in pediatric patients below the age of 3 years has not been established (see CLINICAL PHARMACOLOGY, Clinical Studies ).
PREGNANCY
Pregnancy Pregnancy Category C: Gabapentin has been shown to be fetotoxic in rodents, causing delayed ossification of several bones in the skull, vertebrae, forelimbs, and hindlimbs.
These effects occurred when pregnant mice received oral doses of 1000 or 3000 mg/kg/day during the period of organogenesis, or approximately 1 to 4 times the maximum dose of 3600 mg/day given to epileptic patients on a mg/m2 basis.
The no-effect level was 500 mg/kg/day or approximately ½ of the human dose on a mg/m2 basis.
When rats were dosed prior to and during mating, and throughout gestation, pups from all dose groups (500, 1000 and 2000 mg/kg/day) were affected.
These doses are equivalent to less than approximately 1 to 5 times the maximum human dose on a mg/m2 basis.
There was an increased incidence of hydroureter and/or hydronephrosis in rats in a study of fertility and general reproductive performance at 2000 mg/kg/day with no effect at 1000 mg/kg/day, in a teratology study at 1500 mg/kg/day with no effect at 300 mg/kg/day, and in a perinatal and postnatal study at all doses studied (500, 1000 and 2000 mg/kg/day).
The doses at which the effects occurred are approximately 1 to 5 times the maximum human dose of 3600 mg/day on a mg/m2 basis; the no-effect doses were approximately 3 times (Fertility and General Reproductive Performance study) and approximately equal to (Teratogenicity study) the maximum human dose on a mg/m2 basis.
Other than hydroureter and hydronephrosis, the etiologies of which are unclear, the incidence of malformations was not increased compared to controls in offspring of mice, rats, or rabbits given doses up to 50 times (mice), 30 times (rats), and 25 times (rabbits) the human daily dose on a mg/kg basis, or 4 times (mice), 5 times (rats), or 8 times (rabbits) the human daily dose on a mg/m2 basis.
In a teratology study in rabbits, an increased incidence of postimplantation fetal loss occurred in dams exposed to 60, 300, and 1500 mg/kg/day, or less than approximately 1/4 to 8 times the maximum human dose on a mg/m2 basis.
There are no adequate and well-controlled studies in pregnant women.
This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
To provide information regarding the effects of in utero exposure to gabapentin, physicians are advised to recommend that pregnant patients taking gabapentin enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry.
This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves.
Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/.
NUSRING MOTHERS
Use in Nursing Mothers Gabapentin is secreted into human milk following oral administration.
A nursed infant could be exposed to a maximum dose of approximately 1 mg/kg/day of gabapentin.
Because the effect on the nursing infant is unknown, gabapentin should be used in women who are nursing only if the benefits clearly outweigh the risks.
INFORMATION FOR PATIENTS
Information for Patients Inform patients of the availability of a Medication Guide, and instruct them to read the Medication Guide prior to taking gabapentin.
Instruct patients to take gabapentin only as prescribed.
Patients, their caregivers, and families should be counseled that AEDs, including gabapentin,may increase the risk of suicidal thoughts and behavior and should be advised 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.
Behaviors of concern should be reported immediately to healthcare providers.
Patients should be advised that gabapentin may cause dizziness, somnolence and other symptoms and signs of CNS depression.
Accordingly, they should be advised neither to drive a car nor to operate other complex machinery until they have gained sufficient experience on gabapentin to gauge whether or not it affects their mental and/or motor performance adversely.
Patients who require concomitant treatment with morphine may experience increases in gabapentin concentrations.
Patients should be carefully observed for signs of CNS depression, such as somnolence, and the dose of gabapentin or morphine should be reduced appropriately (see Drug Interactions ).
Patients should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant.
This registry is collecting information about the safety of antiepileptic drugs during pregnancy.
To enroll, patients can call the toll free number 1-888-233-2334 (see PRECAUTIONS, Pregnancy section).
DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION Gabapentin tablets USP are given orally with or without food.
Patients should be informed that, should they break the scored 600 or 800 mg tablet in order to administer a half-tablet, they should take the unused half-tablet as the next dose.
Half-tablets not used within several days of breaking the scored tablet should be discarded.
If gabapentin tablets USP dose is reduced, discontinued or substituted with an alternative medication, this should be done gradually over a minimum of 1 week (a longer time period may be needed at the discretion of the prescriber).
Postherpetic Neuralgia In adults with postherpetic neuralgia, gabapentin therapy may be initiated as a single 300 mg dose on Day 1, 600 mg/day on Day 2 (divided BID), and 900 mg/day on Day 3 (divided TID).
The dose can subsequently be titrated up as needed for pain relief to a daily dose of 1800 mg (divided TID).
In clinical studies, efficacy was demonstrated over a range of doses from 1800 mg/day to 3600 mg/day with comparable effects across the dose range.
Additional benefit of using doses greater than 1800 mg/day was not demonstrated.
Epilepsy Gabapentin tablets USP, are recommended for add-on therapy in patients 3 years of age and older.
Effectiveness in pediatric patients below the age of 3 years has not been established.
Patients >12 years of age: The effective dose of gabapentin is 900 to 1800 mg/day and given in divided doses (three times a day) using 300 or 400 mg capsules, 600 or 800 mg tablets.
The starting dose is 300 mg three times a day.
If necessary, the dose may be increased using 300 or 400 mg capsules, 600 or 800 mg tablets three times a day up to 1800 mg/day.
Dosages up to 2400 mg/day have been well tolerated in long-term clinical studies.
Doses of 3600 mg/day have also been administered to a small number of patients for a relatively short duration, and have been well tolerated.
The maximum time between doses in the TID schedule should not exceed 12 hours.
Pediatric Patients Age 3 to 12 years: The starting dose should range from 10 to 15 mg/kg/day in 3 divided doses, and the effective dose reached by upward titration over a period of approximately 3 days.
The effective dose of gabapentin in patients 5 years of age and older is 25 to 35 mg/kg/day and given in divided doses (three times a day).
The effective dose in pediatric patients ages 3 and 4 years is 40 mg/kg/day and given in divided doses (three times a day) (see CLINICAL PHARMACOLOGY, Pediatrics).
Gabapentin may be administered as the oral solution, capsule, or tablet, or using combinations of these formulations.
Dosages up to 50 mg/kg/day have been well tolerated in a long-term clinical study.
The maximum time interval between doses should not exceed 12 hours.
It is not necessary to monitor gabapentin plasma concentrations to optimize gabapentin therapy.
Further, because there are no significant pharmacokinetic interactions among gabapentin and other commonly used antiepileptic drugs, the addition of gabapentin does not alter the plasma levels of these drugs appreciably.
If gabapentin tablets are discontinued and/or an alternate anticonvulsant medication is added to the therapy, this should be done gradually over a minimum of 1 week.
Dosage in Renal Impairment Creatinine clearance is difficult to measure in outpatients.
In patients with stable renal function, creatinine clearance (CCr) can be reasonably well estimated using the equation of Cockcroft and Gault: for females CCr =(0.85)(140-age)(weight)/[(72)(SCr)] for males CCr =(140-age)(weight)/[(72)(SCr)] where age is in years, weight is in kilograms and SCr is serum creatinine in mg/dL.
Dosage adjustment in patients ≥12 years of age with compromised renal function or undergoing hemodialysis is recommended as follows (see dosing recommendations above for effective doses in each indication).
TABLE 6.
Gabapentin Dosage Based on Renal Function Renal Function Creatinine Clearance (mL/min) Total Daily Dose Range (mg/day) Dose Regimen (mg) ≥60 900 to 3600 300 TID 400 TID 600 TID 800 TID 1200 TID >30 to 59 400 to 1400 200 BID 300 BID 400 BID 500 BID 700 BID >15 to 29 200 to 700 200 QD 300 QD 400 QD 500 QD 700 QD 15For patients with creatinine clearance <15 mL/min, reduce daily dose in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7.5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive).
100 to 300 100 QD 125 QD 150 QD 200 QD 300 QD Post-Hemodialysis Supplemental Dose (mg)Patients on hemodialysis should receive maintenance doses based on estimates of creatinine clearance as indicated in the upper portion of the table and a supplemental post-hemodialysis dose administered after each 4 hours of hemodialysis as indicated in the lower portion of the table.
Hemodialysis 125 150 200 250 350 The use of gabapentin tablets USP in patients <12 years of age with compromised renal function has not been studied.
Dosage in Elderly Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients.