Gabapentin

The following serious adverse reactions are discussed in greater detail in other sections:

• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity [see WARNINGS AND PRECAUTIONS]
• Anaphylaxis and Angioedema [see WARNINGS AND PRECAUTIONS]
• Somnolence/Sedation and Dizziness [see WARNINGS AND PRECAUTIONS]
• Withdrawal Precipitated Seizure, Status Epilepticus [see WARNINGS AND PRECAUTIONS]
• Suicidal Behavior and Ideation [see WARNINGS AND PRECAUTIONS]
• Neuropsychiatric Adverse Reactions (Pediatric Patients 3–12 Years of Age) [see WARNINGS AND PRECAUTIONS]
• Sudden and Unexplained Death in Patients with Epilepsy [see WARNINGS AND PRECAUTIONS]

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.

The most common adverse reactions associated with the use of NEURONTIN in adults, not seen at an equivalent frequency among placebo-treated patients, were dizziness, somnolence, and peripheral edema.

In the 2 controlled trials in postherpetic neuralgia, 16% of the 336 patients who received NEURONTIN and 9% of the 227 patients who received placebo discontinued treatment because of an adverse reaction. The adverse reactions that most frequently led to withdrawal in NEURONTIN-treated patients were dizziness, somnolence, and nausea.

Table 3 lists adverse reactions that occurred in at least 1% of NEURONTIN-treated patients with postherpetic neuralgia participating in placebo-controlled trials and that were numerically more frequent in the NEURONTIN group than in the placebo group.

TABLE 3. Adverse Reactions in Pooled Placebo-Controlled Trials in Postherpetic Neuralgia

Other reactions in more than 1% of patients but equally or more frequent in the placebo group included pain, tremor, neuralgia, back pain, dyspepsia, dyspnea, and flu syndrome.

There were no clinically important differences between men and women in the types and incidence of adverse reactions. Because there were few patients whose race was reported as other than white, there are insufficient data to support a statement regarding the distribution of adverse reactions by race.

The most common adverse reactions with NEURONTIN in combination with other antiepileptic drugs in patients >12 years of age, not seen at an equivalent frequency among placebo-treated patients, were somnolence, dizziness, ataxia, fatigue, and nystagmus.

The most common adverse reactions with NEURONTIN in combination with other antiepileptic drugs in pediatric patients 3 to 12 years of age, not seen at an equal frequency among placebo-treated patients, were viral infection, fever, nausea and/or vomiting, somnolence, and hostility [see WARNINGS AND PRECAUTIONS].

Approximately 7% of the 2074 patients >12 years of age and approximately 7% of the 449 pediatric patients 3 to 12 years of age who received NEURONTIN in premarketing clinical trials discontinued treatment because of an adverse reaction. The adverse reactions most commonly associated with withdrawal in patients >12 years of age were somnolence (1.2%), ataxia (0.8%), fatigue (0.6%), nausea and/or vomiting (0.6%), and dizziness (0.6%). The adverse reactions most commonly associated with withdrawal in pediatric patients were emotional lability (1.6%), hostility (1.3%), and hyperkinesia (1.1%).

Table 4 lists adverse reactions that occurred in at least 1% of NEURONTIN-treated patients >12 years of age with epilepsy participating in placebo-controlled trials and were numerically more common in the NEURONTIN group. In these studies, either NEURONTIN or placebo was added to the patient's current antiepileptic drug therapy.

TABLE 4. Adverse Reactions in Pooled Placebo-Controlled Add-On Trials In Epileps y Patients >12 years of age

Among the adverse reactions occurring at an incidence of at least 10% in NEURONTIN-treated patients, somnolence and ataxia appeared to exhibit a positive dose-response relationship.

The overall incidence of adverse reactions and the types of adverse reactions seen were similar among men and women treated with NEURONTIN. The incidence of adverse reactions increased slightly with increasing age in patients treated with either NEURONTIN or placebo. Because only 3% of patients (28/921) in placebo-controlled studies were identified as nonwhite (black or other), there are insufficient data to support a statement regarding the distribution of adverse reactions by race.

Table 5 lists adverse reactions that occurred in at least 2% of NEURONTIN-treated patients, age 3 to 12 years of age with epilepsy participating in placebo-controlled trials, and which were numerically more common in the NEURONTIN group.

TABLE 5. Adverse Reactions in a Placebo-Controlled Add-On Trial in Pediatric Epilepsy Patients Age 3 to 12 Years

Other reactions in more than 2% of pediatric patients 3 to 12 years of age but equally or more frequent in the placebo group included: pharyngitis, upper respiratory infection, headache, rhinitis, convulsions, diarrhea, anorexia, coughing, and otitis media.

Postmarketing Experience

The following adverse reactions have been identified during postmarketing use of NEURONTIN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hepatobiliary disorders: jaundice

Investigations: elevated creatine kinase, elevated liver function tests

Metabolism and nutrition disorders: hyponatremia

Musculoskeletal and connective tissue disorder: rhabdomyolysis

Nervous system disorders: movement disorder

Reproductive system and breast disorders: breast enlargement, changes in libido, ejaculation disorders and anorgasmia

Skin and subcutaneous tissue disorders: angioedema [see WARNINGS AND PRECAUTIONS], erythema multiforme, Stevens-Johnson syndrome.

Adverse reactions following the abrupt discontinuation of gabapentin have also been reported. The most frequently reported reactions were anxiety, insomnia, nausea, pain, and sweating.

NEURONTIN
(Neu ron' tin)
(Gabapentin) Capsules, Tablets, and Oral Solution

Read the Medication Guide before you start taking NEURONTIN 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 NEURONTIN?

Do not stop taking NEURONTIN without first talking to your healthcare provider.

Stopping NEURONTIN suddenly can cause serious problems.

NEURONTIN can cause serious side effects including:

1. Suicidal Thoughts. Like other antiepileptic drugs, NEURONTIN 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 NEURONTIN without first talking to a healthcare provider.

   • Stopping NEURONTIN 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 NEURONTIN in children 3 to 12 years of age can cause emotional changes, aggressive behavior, problems with concentration, restlessness, changes in school performance, and hyperactivity.
3. NEURONTIN may cause serious or life-threatening allergic reactions that may affect your skin or other parts of your body such as your liver or blood cells. This may cause you to be hospitalized or to stop NEURONTIN. You may or may not have a rash with an allergic reaction caused by NEURONTIN. Call a healthcare provider right away if you have any of the following symptoms:
   • skin rash
   • hives
   • difficulty breathing
   • fever
   • swollen glands that do not go away
   • swelling of your face, lips, throat, or tongue
   • yellowing of your skin or of the whites of the eyes
   • unusual bruising or bleeding
   • severe fatigue or weakness
   • unexpected muscle pain
   • frequent infections
   These symptoms may be the first signs of a serious reaction. A healthcare provider should examine you to decide if you should continue taking NEURONTIN.

What is NEURONTIN?

NEURONTIN 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 with seizures.

Who should not take NEURONTIN?

Do not take NEURONTIN if you are allergic to gabapentin or any of the other ingredients in NEURONTIN. See the end of this Medication Guide for a complete list of ingredients in NEURONTIN.

What should I tell my healthcare provider before taking NEURONTIN?

Before taking NEURONTIN, 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
• have diabetes
• are pregnant or plan to become pregnant. It is not known if NEURONTIN can harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking NEURONTIN. You and your healthcare provider will decide if you should take NEURONTIN while you are pregnant.
  • If you become pregnant while taking NEURONTIN, 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 breast-feeding or plan to breast-feed. NEURONTIN can pass into breast milk. You and your healthcare provider should decide how you will feed your baby while you take NEURONTIN.

Tell your healthcare provider about all the medicines you take, including prescription and over-thecounter medicines, vitamins, and herbal supplements.

Taking NEURONTIN 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 NEURONTIN?

• Take NEURONTIN exactly as prescribed. Your healthcare provider will tell you how much NEURONTIN to take.
  • Do not change your dose of NEURONTIN without talking to your healthcare provider.
  • If you take NEURONTIN tablets and break a tablet in half, the unused half of the tablet should be taken at your next scheduled dose. Half tablets not used within 28 days of breaking should be thrown away.
  • Take NEURONTIN capsules with water.
• NEURONTIN tablets 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 NEURONTIN. If you take too much NEURONTIN, call your healthcare provider or your local Poison Control Center right away at 1-800-222-1222.

What should I avoid while taking NEURONTIN?

• Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking NEURONTIN without first talking with your healthcare provider. Taking NEURONTIN 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 NEURONTIN affects you. NEURONTIN can slow your thinking and motor skills.

What are the possible side effects of NEURONTIN?

NEURONTIN may cause serious side effects including:

See "What is the most important information I should know about NEURONTIN?"

• problems driving while using NEURONTIN. See "What I should avoid while taking Neurontin?"
• sleepiness and dizziness, which could increase the occurrence of accidental injury, including falls
• The most common side effects of NEURONTIN include:
  • lack of coordination
  • viral infection
  • feeling drowsy
  • nausea and vomiting
  • difficulty with speaking
  • tremor
  • swelling, usually of legs and feet
  • feeling tired
  • fever
  • jerky movements
  • 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 NEURONTIN. 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 NEURONTIN?

• Store NEURONTIN Capsules and Tablets between 68°F to 77°F (20°C to 25°C).
• Store NEURONTIN Oral Solution in the refrigerator between 36°F to 46°F (2°C to 8°C).

Keep NEURONTIN and all medicines out of the reach of children.

General information about the safe and effective use of NEURONTIN

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use NEURONTIN for a condition for which it was not prescribed. Do not give NEURONTIN 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 NEURONTIN. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about NEURONTIN that was written for healthcare professionals.

For more information go to http://www.pfizer.com or call 1-800-438-1985.

What are the ingredients in NEURONTIN?

Active ingredient: gabapentin

Inactive ingredients in the capsules: lactose, cornstarch, talc, gelatin, titanium dioxide and FD&C Blue No. 2.

The 300-mg capsule shell also contains: yellow iron oxide.

The 400-mg capsule shell also contains: red iron oxide, and yellow iron oxide.

Inactive ingredients in the tablets: poloxamer 407, copovidone, cornstarch, magnesium stearate, hydroxypropyl cellulose, talc, and candelilla wax

Inactive ingredients in the oral solution: glycerin, xylitol, purified water, and artificial flavor.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Gabapentin is part of the drug class:

• Other antiepileptics

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. 
• are breastfeeding or plan to breastfeed. 

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.

General

• Closely monitor for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.55 56 57 59 60 61 (See Suicidality Risk under Cautions.)

• If therapy is discontinued, gradually decrease dosage to avoid manifestations of abrupt withdrawal.1 60 61 (See Dosage under Dosage and Administration, and also see Withdrawal Seizures under Cautions.)

Administration

Oral Administration

Gabapentin: Commercially available as conventional (immediate-release) capsules, tablets, or oral solution.1 Also available as gastroretentive tablets (Gralise); although not considered by FDA to be an extended-release formulation, the gastroretentive tablets are sometimes referred to in this manner because of similar pharmacokinetics to an extended-release dosage form.60 62 63 64 65 Because of differences in pharmacokinetics that affect frequency of administration, gabapentin gastroretentive tablets are not interchangeable with other gabapentin preparations.60 (See Pharmacokinetics.)

Gabapentin enacarbil: Commercially available as extended-release tablets (Horizant).61 Because of differences in pharmacokinetics that affect frequency of administration, gabapentin enacarbil extended-release tablets are not interchangeable with other gabapentin preparations.61 (See Pharmacokinetics.)

Administer orally 3 times daily without regard to meals.1 Interval between doses should not exceed 12 hours.1

If film-coated scored tablets containing 600 or 800 mg of gabapentin are divided to administer a 300- or 400-mg dose, use the remaining half tablet for the next dose.1 Discard half tablets that are not used within 28 days.1

Swallow capsules whole with water.1

Administer orally once daily with the evening meal.60 Swallow tablets whole; do not chew, crush, or split.60

Administer orally once or twice daily depending on indication.61

When used for restless legs syndrome, administer once daily at about 5 p.m.; if a dose is missed, take next dose the following day as scheduled.61

When used for PHN, administer orally twice daily; if a dose is missed, skip dose and take next dose at regularly scheduled time.61

Swallow tablets whole; do not crush, chew, or cut.61

Dosage

Pediatric Patients

Gabapentin conventional (immediate-release) tablets, capsules, or oral solution in children 3–11 years of age: Initially, 10–15 mg/kg daily in 3 divided doses.1 Interval between doses should not exceed 12 hours.1 Titrate upward over a period of approximately 3 days until an effective maintenance dosage is achieved.1 Recommended maintenance dosage in children 3–4 years of age is 40 mg/kg daily in 3 divided doses; recommended maintenance dosage in children 5–11 years of age is 25–35 mg/kg daily in 3 divided doses.1 Dosages up to 50 mg/kg daily have been well tolerated in clinical studies.1

Gabapentin conventional (immediate-release) tablets, capsules, or oral solution in children ≥12 years of age: Initially, 300 mg 3 times daily.1 Maintenance dosage of 300–600 mg 3 times daily recommended.1 Interval between doses should not exceed 12 hours.1 Dosages up to 2.4 g daily have been well tolerated in long-term clinical studies, and a small number of patients have tolerated dosages of 3.6 g daily for short periods.1

If therapy is discontinued, dosage reduced, or an alternative drug substituted, such changes should be done gradually over ≥1 week.1

Adults

Gabapentin conventional (immediate-release) tablets, capsules, or oral solution: Initially, 300 mg 3 times daily.1 Maintenance dosage of 300–600 mg 3 times daily recommended.1 Interval between doses should not exceed 12 hours.1 Dosages up to 2.4 g daily have been well tolerated in long-term clinical studies, and a small number of patients have tolerated dosages of 3.6 g daily for short periods.1

If therapy is discontinued, dosage reduced, or an alternative drug substituted, such changes should be done gradually over ≥1 week.1

Gabapentin conventional (immediate-release) tablets, capsules, or oral solution: 300 mg on day 1, 300 mg twice daily on day 2, and 300 mg 3 times daily on day 3.1 Increase dosage as needed for relief of pain up to a total dosage of 1.8 g daily in 3 divided doses.1 No evidence of additional benefit with dosages >1.8 g daily.1 If therapy is discontinued, dosage reduced, or an alternative drug substituted, such changes should be done gradually over ≥1 week.1

Gabapentin gastroretentive tablets (Gralise): Titrate gradually over 2 weeks up to recommended maintenance dosage of 1.8 g once daily as follows: 300 mg once daily on day 1, 600 mg once daily on day 2, 900 mg once daily on days 3–6, 1.2 g once daily on days 7–10, 1.5 g once daily on days 11–14, and 1.8 g once daily on day 15.60 If therapy is discontinued, dosage reduced, or an alternative drug substituted, such changes should be done gradually over ≥1 week.60

Gabapentin enacarbil extended-release tablets (Horizant): Initially, 600 mg once daily in the morning for 3 days, then increase to recommended maintenance dosage of 600 mg twice daily.61 Dosages >1.2 g daily provide no additional benefit and associated with an increased incidence of adverse effects.61 When discontinuing therapy in patients receiving a dosage of 600 mg twice daily, reduce to 600 mg once daily for 1 week prior to withdrawing therapy.61

Dosages of gabapentin 900 mg to 3.6 g daily have been used; however, pain relief generally observed in patients receiving dosages >1.8 g daily.24 25

Gabapentin enacarbil extended-release tablets (Horizant): 600 mg once daily at approximately 5 p.m.61

When discontinuing therapy, gradual withdrawal only necessary in patients receiving higher than recommended dosages; in such cases, reduce dosage to 600 mg once daily for 1 week prior to withdrawing therapy.61

300 mg 3 times daily as gabapentin conventional (immediate-release) preparations has been effective; higher dosages may provide additional benefit.30 31 37

Special Populations

Renal Impairment

Adjust dosage of gabapentin or gabapentin enacarbil in patients with renal impairment based on Clcr (see Tables 1–4).1 60 61

Geriatric Patients

Select dosage carefully, usually initiating therapy at the low end of the dosage range.1 Adjust dosage based on Clcr.1 (See Renal Impairment under Dosage and Administration.)

• Mechanism of anticonvulsant action is unknown.1 4 5 7 8 9 Does not bind to GABA receptors,1 4 5 6 7 17 affect GABA reuptake or metabolism, 1 6 7 17 or act as a precursor of GABA or other substances active at GABA receptors.1 17

• Mechanism of analgesic action is unknown.1 20 21 22 23 Prevents allodynia (pain-related behavior in response to normally innocuous stimuli) and hyperalgesia (exaggerated response to painful stimuli) in several animal models of neuropathic pain.1 20 Decreases pain-related responses after peripheral inflammation in animals; however, has not altered immediate pain-related behaviors, and clinical relevance is not known.1 In vitro studies demonstrate that the drug binds with high affinity to the α2δ subunit of voltage-activated calcium channels; however, clinical relevance not known.1 66 69

Gabapentin capsules, USP are contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients.

8.1 Pregnancy

Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. In nonclinical studies in mice, rats, and rabbits, Gabapentin was developmentally toxic when administered to pregnant animals at doses similar to or lower than those used clinically. Gabapentin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

When pregnant mice received oral doses of Gabapentin (500, 1000, or 3000 mg/kg/day) during the period of organogenesis, embryo-fetal toxicity (increased incidences of skeletal variations) was observed at the two highest doses. The no-effect dose for embryo-fetal developmental toxicity in mice was 500 mg/kg/day or approximately ½ of the maximum recommended human dose (MRHD) of 3600 mg/kg on a body surface area (mg/m 2) basis.

In studies in which rats received oral doses of Gabapentin (500 to 2000 mg/kg/day), during pregnancy, adverse effect on offspring development (increased incidences of hydroureter and/or hydronephrosis) were observed at all doses. The lowest effect dose for developmental toxicity in rats is approximately equal to the MRHD on a mg/m 2 basis.

When pregnant rabbits were treated with Gabapentin during the period of organogenesis, an increase in embryo-fetal mortality was observed at all doses tested (60, 300, or 1500 mg/kg). The lowest effect dose for embryo-fetal developmental toxicity in rabbits is less than the MRHD on a mg/m 2 basis.

In a published study, Gabapentin (400 mg/kg/day) was administered by intraperitoneal injection to neonatal mice during the first postnatal week, a period of synaptogenesis in rodents (corresponding to the last trimester of pregnancy in humans). Gabapentin caused a marked decrease in neuronal synapse formation in brains of intact mice and abnormal neuronal synapse formation in a mouse model of synaptic repair. Gabapentin has been shown in vitro to interfere with activity of the α2δ subunit of voltage-activated calcium channels, a receptor involved in neuronal synaptogenesis. The clinical significance of these findings is unknown.

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/.

8.3 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.

8.4 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 STUDIES (14.2)].

8.5 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 reactions 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 DOSAGE AND ADMINISTRATION (2.4), ADVERSE REACTIONS (6), and CLINICAL PHARMACOLOGY (12.3)].

8.6 Renal Impairment

Dosage adjustment in adult patients with compromised renal function is necessary [see DOSAGE AND ADMINISTRATION (2.3) and CLINICAL PHARMACOLOGY (12.3)]. Pediatric patients with renal insufficiency have not been studied.

Dosage adjustment in patients undergoing hemodialysis is necessary [see DOSAGE AND ADMINISTRATION (2.3) and CLINICAL PHARMACOLOGY (12.3)].

The active ingredient in Gabapentin capsules, USP is Gabapentin, USP which has the chemical name 1-(aminomethyl)cyclohexaneacetic acid. The molecular formula of Gabapentin is C 9H 17NO 2 and the molecular weight is 171.24. The structural formula of Gabapentin is:

Gabapentin, USP 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.

Each Gabapentin, USP capsule contains 100 mg, 300 mg, or 400 mg of Gabapentin and the following inactive ingredients: magnesium stearate, pregelatinized starch (corn), starch (corn) and talc. The 100 mg capsule shell contains gelatin, sodium lauryl sulfate and titanium dioxide. The 300 mg capsule shell contains gelatin, sodium lauryl sulfate, titanium dioxide, and iron oxide yellow. The 400 mg capsule shell contains gelatin, sodium lauryl sulfate, titanium dioxide, FD&C Yellow No.6 and FD&C Blue No.1.

Gabapentin (GA-be-PEN-tin) Capsules

Read the Medication Guide before you start taking Gabapentin capsules 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 capsules? Do not stop taking Gabapentin capsules without first talking to your healthcare provider.

Stopping Gabapentin capsules suddenly can cause serious problems.

Gabapentin capsules can cause serious side effects including:

1. Suicidal Thoughts. Like other antiepileptic drugs, Gabapentin capsules 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 capsules without first talking to a healthcare provider.

• Stopping Gabapentin capsules 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 capsules in children 3 to 12 years of age can cause emotional changes, aggressive behavior, problems with concentration, restlessness, changes in school performance, and hyperactivity.

3. Gabapentin capsules may cause serious or life-threatening allergic reactions that may affect your skin or other parts of your body such as your liver or blood cells. This may cause you to be hospitalized or to stop Gabapentin capsules. You may or may not have a rash with an allergic reaction caused by Gabapentin capsules. Call a healthcare provider right away if you have any of the following symptoms:

• skin rash
• hives
• difficulty breathing
• fever
• swollen glands that do not go away
• swelling of your face, lips, throat, or tongue
• yellowing of your skin or of the whites of the eyes
• unusual bruising or bleeding
• severe fatigue or weakness
• unexpected muscle pain
• frequent infections

These symptoms may be the first signs of a serious reaction. A healthcare provider should examine you to decide if you should continue taking Gabapentin capsules.

What are Gabapentin capsules?

Gabapentin capsules are 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 with seizures.

Who should not take Gabapentin capsules?

Do not take Gabapentin capsules if you are allergic to Gabapentin or any of the other ingredients in Gabapentin capsules. See the end of this Medication Guide for a complete list of ingredients in Gabapentin capsules.

Before taking Gabapentin capsules, 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
• have diabetes
• are pregnant or plan to become pregnant. It is not known if Gabapentin capsules can harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking Gabapentin capsules. You and your healthcare provider will decide if you should take Gabapentin capsules while you are pregnant.
• If you become pregnant while taking Gabapentin capsules, 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 breast-feeding or plan to breast-feed. Gabapentin can pass into breast milk. You and your healthcare provider should decide how you will feed your baby while you take Gabapentin capsules.
• What should I tell my healthcare provider before taking Gabapentin capsules?

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Taking Gabapentin capsules 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 capsules?

• Take Gabapentin capsules exactly as prescribed. Your healthcare provider will tell you how much Gabapentin capsules to take.
• Do not change your dose of Gabapentin capsules without talking to your healthcare provider.
• Take Gabapentin capsules with water.
• Gabapentin capsules 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 capsules.

If you take too much Gabapentin capsules, call your healthcare provider or your local Poison Control Center right away at 1-800-222-1222.

What should I avoid while taking Gabapentin capsules?

• Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking Gabapentin capsules without first talking with your healthcare provider. Taking Gabapentin capsules 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 capsules affects you. Gabapentin capsules can slow your thinking and motor skills.

What are the possible side effects of Gabapentin capsules?

Gabapentin capsules may cause serious side effects including:

See “What is the most important information I should know about Gabapentin capsules?

• problems driving while using Gabapentin capsules. See “What I should avoid while taking Gabapentin capsules?”
• sleepiness and dizziness, which could increase the occurrence of accidental injury, including falls
• The most common side effects of Gabapentin capsules include:
• lack of coordination
• viral infection
• feeling drowsy
• nausea and vomiting
• difficulty with speaking
• tremor
• swelling, usually of legs and feet
• feeling tired
• fever
• jerky movements
• 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 capsules. 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 capsules?

Store Gabapentin Capsules between 68°F to 77°F (20°C to 25°C).

Keep Gabapentin capsules and all medicines out of the reach of children.

General information about the safe and effective use of Gabapentin capsules

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Gabapentin capsules for a condition for which it was not prescribed. Do not give Gabapentin capsules 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 capsules. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about Gabapentin capsules that was written for healthcare professionals.

What are the ingredients in Gabapentin capsules?

Active ingredient: Gabapentin, USP

Inactive ingredients in the capsules: magnesium stearate, pregelatinized starch (corn), starch (corn) and talc.

For more information go to WWW.AMNEAL.COM or call 1-877-835-5472.

The 100-mg capsule shell contains: gelatin, sodium lauryl sulfate, and titanium dioxide.

The 300-mg capsule shell contains: gelatin, sodium lauryl sulfate, titanium dioxide, and iron oxide yellow.

The 400-mg capsule shell contains: gelatin, sodium lauryl sulfate, titanium dioxide, FD&C Yellow No. 6, and FD&C Blue No. 1.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

This product’s label may have been updated. For current full prescribing information, please visit www.amneal.com

*Trademarks are the property of their respective owners.

Manufactured by:
Amneal Pharmaceuticals Pvt. Ltd.
Ahmedabad, INDIA 382220

Distributed by:
Amneal Pharmaceuticals
Bridgewater, NJ 08807

Rev. 10-2015-04

(GA ba pen tin)

• Anticonvulsant, Miscellaneous
• GABA Analog

Gabapentin is structurally related to GABA. However, it does not bind to GABAA or GABAB receptors, and it does not appear to influence synthesis or uptake of GABA. High affinity gabapentin binding sites have been located throughout the brain; these sites correspond to the presence of voltage-gated calcium channels specifically possessing the alpha-2-delta-1 subunit. This channel appears to be located presynaptically, and may modulate the release of excitatory neurotransmitters which participate in epileptogenesis and nociception.

Absorption

Variable, from proximal small bowel by L-amino transport system; saturable process; dose-dependent

Distribution

Vd: 58 ± 6 L; CSF concentrations are ~20% of plasma concentrations

Metabolism

Not metabolized

Excretion

Proportional to renal function; urine (as unchanged drug)

Clearance: Apparent oral clearance is directly proportional to CrCl: Clearance in infants is highly variable; oral clearance (per kg) in children <5 years of age is higher than in children ≥5 years of age

Time to Peak

Immediate release: Infants 1 month to Children 12 years: 2 to 3 hours; Adults: 2 to 4 hours; Gralise: 8 hours

Half-Life Elimination

Infants 1 month to Children 12 years: 4.7 hours

Adults, normal: 5 to 7 hours; increased half-life with decreased renal function; anuric adult patients: 132 hours; adults during hemodialysis: 3.8 hours

Protein Binding

<3%

In CrCl less than 30 mL/minute, half-life is approximately 52 hours (immediate release). In moderate and severe renal impairment, Cl was decreased to 3 and 1 L/hour, respectively, compared with 5 to 7 L/hour in nonrenal impairment patients (ER).

The half-life in anuric patients is approximately 132 hours on nondialysis days; during dialysis, half-life is reduced to 3.8 hours (immediate release). Gabapentin is significantly removed by hemodialysis.

Alcohol dependence

Data from randomized, double-blind, placebo-controlled studies supports the use of gabapentin in the maintenance of abstinence in patients with alcohol dependence [Brower 2008], [Furieri 2007], [Mason 2014]. Additional trials may be necessary to further define the role of gabapentin in this condition.

Based on the VA/DoD clinical practice guideline for the management of substance use disorders, gabapentin given for moderate to severe alcohol use disorder is effective and suggested when first-line pharmacotherapy is contraindicated or ineffective [VA/DoD 2015].

Alcohol withdrawal

Data from a randomized, double-blind, active-controlled study supports the use of gabapentin in the treatment of alcohol withdrawal [Myrick 2009]. Additional trials may be necessary to further define the role of gabapentin in this condition.

Based on the VA/DoD clinical practice guideline for the management of substance use disorders, gabapentin given for mild to moderate alcohol withdrawal is effective and suggested when the risk of benzodiazepines outweigh the benefits (ie, inadequate monitoring available, abuse liability, contraindication, adverse reaction) [VA/DoD 2015].

Brachioradial pruritus

Data from a limited number of patients suggest that gabapentin may be beneficial for the treatment of brachioradial pruritus [Bueller 1999], [Carvalho 2015], [Kanitakis 2006], [Winhoven 2004], [Yilmaz 2010]. Additional data may be necessary to further define the role of gabapentin in this condition.

Based on European Dermatology Forum and European Academy of Dermatology and Venerology guidelines for the treatment of chronic pruritus, gabapentin is recommended for chronic pruritus of neuropathic origin. Evidence for brachioradial pruritus in based on anecdotal (case report) data [EDF/EADV [Weisshaar 2012]].

Cough, chronic (refractory)

Data from a small, randomized, double-blind, placebo-controlled trial showed that gabapentin significantly improved cough-specific quality of life in patients with refractory chronic cough compared to placebo. Participants with central sensitization of the cough reflex exhibited a greater response to gabapentin treatment compared to participants without central sensitization [Ryan 2012]. Additional trials may be necessary to further define the role of gabapentin in this condition.

Based on the American College of Chest Physicians guidelines for the treatment of unexplained chronic cough, gabapentin, on a therapeutic trial basis, is suggested in patients with unexplained chronic cough as long as the potential side-effects and risk-benefit profile are discussed prior to use, and there is reassessment at 6 months prior to continuation of treatment [ACCP [Gibson 2016]].

Diabetic neuropathy

Gabapentin has been evaluated in the management of diabetic neuropathy in several controlled trials. Results were conflicting; gabapentin demonstrated no or little benefit in some trials and comparable activity to amitriptyline or tramadol with acetaminophen in other trials. Guideline recommendations also vary. Gabapentin is considered first-line therapy supported by strong evidence in guidelines by the American Association of Clinical Endocrinologists, American Diabetes Association/Toronto Diabetic Neuropathy Expert Group, and European Federation of Neurological Societies. In contrast, guidelines from the American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation state that gabapentin is probably effective and should be considered alternative treatment for painful diabetic neuropathy based on limited benefit in controlled trials.

Fibromyalgia syndrome

Data from a randomized, double-blind, placebo-controlled study supports the use of gabapentin in the treatment of pain and sleep disturbances associated with fibromyalgia [Arnold 2007]. Additional trials may be necessary to further define the role of gabapentin in this condition.

Hot flashes

Data from controlled trials support the use of gabapentin for the treatment of hot flashes. However, most trials were of short duration (up to 12 weeks), and use of gabapentin may be limited by its adverse effect profile. Additional trials may be necessary to further define the role of gabapentin in this condition.

Evidence-based American and Canadian guidelines recommend gabapentin as an alternative to SSRIs/SSNRIs for the management of hot flashes in natural and medically induced menopause in women.

Neuropathic pain

In a meta-analysis of trials evaluating the treatment of peripheral neuropathy caused by multiple etiologies, including painful polyneuropathy, post-amputation pain, post-traumatic pain, complex regional pain syndrome type II, central post-stroke pain, spinal cord injury pain, multiple sclerosis-associated pain, cancer pain and radiculopathy, gabapentin was shown to be safe and effective [IASP [Finnerup 2015]].

Based on International Association for the Study of Pain (IASP), European Federation of Neurological Societies (EFNS) and Society of Critical Care Medicine (SCCM) guidelines, gabapentin is effective and recommended for the management of peripheral neuropathy.

Post-operative pain (adjunct)

Data from 3 meta-analyses supports the use of preemptive doses of gabapentin to decrease postoperative pain and opioid use [Doleman 2015], [Peng 2007], [Yu 2013]. Additional trials may be necessary to further define the role of gabapentin in this condition.

Restless legs syndrome

Gabapentin in the management of RLS has been evaluated in small controlled trials, demonstrating benefits when compared with placebo. Additional trials may be necessary to further define the role of gabapentin in this condition.

The American Academy of Sleep Medicine guidelines regarding RLS management consider gabapentin effective based on low level evidence and noted that patients with pain symptoms appeared to benefit most. The benefit-risk ratio is unclear. The EFNS/ENS/ESRS task force guidelines consider gabapentin effective for short-term management and possibly effective for long-term management of RLS. Additional study is needed to establish optimal dosing.

Social anxiety disorder

Data from a limited number of patients studied in a double-blind, placebo-controlled trial suggest that gabapentin may be beneficial for the treatment of social anxiety disorder [Pande 1999]. Additional data may be necessary to further define the role of gabapentin in this condition.

Uremic pruritus

Data from randomized, blinded, controlled trials and a meta-analysis supports the use of gabapentin in the treatment of uremic pruritus unresponsive to previous therapy [Gunal 2004], [Naini 2007], [Nofal 2016], [Pongcharoen 2016], [Razeghi 2009]. Additional trials may be necessary to further define the role of gabapentin in this condition.

Based on the European Dermatology Forum and European Academy of Dermatology and Venerology guidelines for the management of chronic pruritus, gabapentin is recommended in the management of chronic kidney disease-associated pruritus [EDF/EADV [Weisshaar 2012]].

Postherpetic neuralgia: Oral:

Day 1: 300 mg, Day 2: 300 mg twice daily, Day 3: 300 mg 3 times daily; dose may be titrated as needed for pain relief (range: 1,800 to 3,600 mg/day in divided doses, daily doses >1,800 mg do not generally show greater benefit)

Gralise only: Day 1: 300 mg, Day 2: 600 mg, Days 3 to 6: 900 mg once daily, Days 7 to 10: 1,200 mg once daily, Days 11 to 14: 1,500 mg once daily, Days ≥15: 1,800 mg once daily

Seizures, partial onset: Oral (excluding Gralise):

Initial: 300 mg 3 times daily; increase dosage based on response and tolerability; usual dosage: 900 to 1,800 mg/day administered in 3 divided doses; doses of up to 2,400 mg/day have been tolerated in long-term clinical studies; up to 3,600 mg/day has been tolerated in short-term studies

Note: If gabapentin is discontinued or if another anticonvulsant is added to therapy, it should be done slowly over a minimum of 1 week.

Alcohol dependence (off-label use): Oral: Immediate release: 300 mg once daily on day 1, followed by dosage escalation, based on response and tolerability, in increments of 300 mg/day up to a target dose of 1,800 mg/day in 3 divided doses (Brower 2008; Mason 2014; VA/DoD 2015).

Alcohol withdrawal (off-label use): Oral: Immediate release: 300 to 400 mg 3 times daily on days 1 through 3, then 300 to 400 mg twice daily on day 4, then discontinue. For breakthrough symptoms during days 1 through 4, consider providing single doses of 100 mg administered up to 3 times daily and a 300 mg dose reserved for the evening (Myrick 2009).

Brachioradial pruritus (off-label use): Oral: Immediate release: Initial: 100 mg 3 times daily; increase dose based on response and tolerability up to 1,800 mg/day (Bueller 1999; Kanitakis 2006; Winhoven 2004; Yilmaz 2010). Additional data may be necessary to further define the role of gabapentin in this condition.

Cough, chronic (refractory) (off-label use): Oral: Immediate release: 300 mg once daily on day 1, followed by dosage escalation in increments of 300 mg/day until cough symptoms cease, side effects are intolerable, or a maximum tolerated dose of 1,800 mg/day given in 2 divided doses is reached (ACCP [Gibson 2016]; Ryan 2012). Additional data may be necessary to further define the role of gabapentin in this condition.

Diabetic neuropathy (off-label use): Oral: Immediate release: 900 to 3,600 mg/day (Bril 2011)

Fibromyalgia syndrome (off-label use): Oral: Immediate release: Initial: 300 mg once daily at bedtime, increase in increments of 300 to 600 mg/day every 1 to 2 weeks based on response and tolerability up to 2,400 mg/day in divided doses. Median dosage in clinical trial was 1,800 mg/day with a range of 1,200 to 2,400 mg/day (Arnold 2007).

Hot flashes (off-label use): Oral: Immediate release: 300 mg once daily at bedtime on day 1, then 300 mg twice daily on day 2, then 300 mg 3 times daily (Butt 2008).

Neuropathic pain (off-label use): Oral: Immediate release: 1,200 to 3,600 mg/day in 3 divided doses (IASP [Finnerup 2015]).

Critically ill patients: Oral: Immediate release: Initial: 100 mg 3 times daily in combination with IV opioids; maintenance: 300 to 1,200 mg 3 times daily; maximum dose: 3,600 mg daily (SCCM [Barr 2013])

Postoperative pain (adjunct) (off-label use): Oral: Immediate release: 300 to 1,200 mg given the night before, 1 to 2 hours prior to surgery or immediately following surgery (Doleman 2015; Peng 2007; Yu 2013)

Restless legs syndrome (RLS) (off-label use): Oral: Immediate release: Initial: 300 mg once daily 2 hours before bedtime. Doses ≥600 mg/day have been given in 2 divided doses (late afternoon and 2 hours before bedtime). Dose may be titrated every 2 weeks until symptom relief achieved (range: 300 to 1,800 mg/day). Suggested maintenance dosing schedule: One-third of total daily dose given at 12 pm, remaining two-thirds total daily dose given at 8 pm. (Garcia-Borreguero 2002; Happe 2003; Saletu 2010; Vignatelli 2006)

Social anxiety disorder (off-label use): Oral: Immediate release: Initial: 300 mg twice daily; increase dose based on response and tolerability in increments of no more than 300 mg/day up to a maximum of 3,600 mg/day given in 3 divided doses. Doses for responders ranged from 900 to 3,600 mg/day in the clinical trial (Pande 1999). Additional data may be necessary to further define the role of gabapentin in this condition.

Uremic pruritus (off-label use): Oral: Immediate release: Initial: 100 mg after dialysis on hemodialysis days; may increase dose based on response and tolerability up to 400 mg after dialysis on hemodialysis days (Gunal 2004; Naini 2007; Nofal 2016; Razeghi 2009).

Concerns related to adverse effects:

• Anaphylaxis/angioedema: May occur after the first dose or at any time during treatment. Discontinue therapy and seek immediate medical care if signs or symptoms of anaphylaxis or angioedema occur.

• CNS depression: May cause CNS depression including somnolence and dizziness, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Multiorgan hypersensitivity: Potentially serious, sometimes fatal multiorgan hypersensitivity (also known as drug reaction with eosinophilia and systemic symptoms [DRESS]) has been reported with some antiepileptic drugs, including gabapentin. Monitor for signs and symptoms of possible disparate manifestations associated with lymphatic, hepatic, renal, cardiac, and/or hematologic systems; fever, rash, and eosinophilia may also be present. Discontinue immediately if suspected.

• Neuropsychiatric effects: Use in pediatric patients with epilepsy has been associated with the occurrence of CNS adverse effects of mild to moderate intensity. The most significant include emotional lability, hostility (eg, aggressive behaviors), changes in behavior and thinking (eg, concentration problems and changes in school performance), and hyperkinesia (primarily restlessness and hyperactivity).

• Suicidal ideation: Pooled analysis of trials involving various antiepileptics (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify healthcare provider immediately if symptoms occur.

Disease-related concerns:

• Renal impairment: Use with caution in patients with severe renal impairment; dose adjustment required.

• Seizure disorder: The safety and efficacy of Gralise has not been studied in patients with epilepsy.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Product interchangeability: Gabapentin immediate release and Gralise products are not interchangeable with each other or with gabapentin enacarbil (Horizant) due to differences in formulations, indications, and pharmacokinetics.

Other warnings/precautions:

• Tumorigenic potential: Male rat studies demonstrated an association with pancreatic adenocarcinoma (clinical implication in humans is unknown).

• Withdrawal: Anticonvulsants should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal. Gralise should be withdrawn over ≥1 week.