Pregabalin

Warnings and Precautions (5.3, 5.4)                                                                       04/2025

Pregabalin capsule is indicated for:

• Management of neuropathic pain associated with diabetic peripheral neuropathy
• Management of postherpetic neuralgia
• Adjunctive therapy for the treatment of partial-onset seizures in patients 1 month of age and older
• Management of fibromyalgia
• Management of neuropathic pain associated with spinal cord injury

• For adult indications, begin dosing at 150 mg/day. For partial-onset seizure dosing in pediatric patients 1 month of age and older, refer to section
  
  
  2.4 Adjunctive Therapy for Partial-Onset Seizures in Patients 1 Month of Age and Older

  The recommended dosages for adults and pediatric patients 1 month of age and older are included in Table 1. Administer the total daily dosage orally in two or three divided doses as indicated in Table 1. In pediatric patients, the recommended dosing regimen is dependent upon body weight. Based on clinical response and tolerability, dosage may be increased, approximately weekly.

  Table 1. Recommended Dosage for Adults and Pediatric Patients 1 Month and Older

  Age and Body Weight	Recommended Initial Dosage	Recommended Maximum Dosage	Frequency of Administration
  Adults (17 years and older)	150 mg/day	600 mg/day	2 or 3 divided doses
  Pediatric patients weighing 30 kg or more	2.5 mg/kg/day	10 mg/kg/day (not to exceed 600 mg/day)	2 or 3 divided doses
  Pediatric patients weighing less than 30 kg	3.5 mg/kg/day	14 mg/kg/day	1 month to less than 4 years of age: 3 divided doses 4 years of age and older : 2 or 3 divided doses

  Both the efficacy and adverse event profiles of pregabalin capsules have been shown to be dose-related.

  The effect of dose escalation rate on the tolerability of pregabalin capsules has not been formally studied.

  The efficacy of adjunctive pregabalin capsules in patients taking gabapentin has not been evaluated in controlled trials. Consequently, dosing recommendations for the use of pregabalin capsules with gabapentin cannot be offered.
  . (
  
  
  2.2 Neuropathic Pain Associated with Diabetic Peripheral Neuropathy in Adults

  The maximum recommended dose of pregabalin capsules are 100 mg three times a day (300 mg/day) in patients with creatinine clearance of at least 60 mL/min. Begin dosing at 50 mg three times a day (150 mg/day). The dose may be increased to 300 mg/day within 1 week based on efficacy and tolerability.

  Although pregabalin capsules were also studied at 600 mg/day, there is no evidence that this dose confers additional significant benefit and this dose was less well tolerated. In view of the dose-dependent adverse reactions, treatment with doses above 300 mg/day is not recommended

  [see Adverse Reactions (6.1)].
  ,
  
  
  2.3 Postherpetic Neuralgia in Adults

  The recommended dose of pregabalin capsules are 75 to 150 mg two times a day, or 50 to 100 mg three times a day (150 to 300 mg/day) in patients with creatinine clearance of at least 60 mL/min. Begin dosing at 75 mg two times a day, or 50 mg three times a day (150 mg/day). The dose may be increased to 300 mg/day within 1 week based on efficacy and tolerability.

  Patients who do not experience sufficient pain relief following 2 to 4 weeks of treatment with 300 mg/day, and who are able to tolerate pregabalin capsules, may be treated with up to 300 mg two times a day, or 200 mg three times a day (600 mg/day). In view of the dose-dependent adverse reactions and the higher rate of treatment discontinuation due to adverse reactions, reserve dosing above 300 mg/day for those patients who have on-going pain and are tolerating 300 mg daily

  [see Adverse Reactions (6.1)].
  ,
  
  
  2.4 Adjunctive Therapy for Partial-Onset Seizures in Patients 1 Month of Age and Older

  The recommended dosages for adults and pediatric patients 1 month of age and older are included in Table 1. Administer the total daily dosage orally in two or three divided doses as indicated in Table 1. In pediatric patients, the recommended dosing regimen is dependent upon body weight. Based on clinical response and tolerability, dosage may be increased, approximately weekly.

  Table 1. Recommended Dosage for Adults and Pediatric Patients 1 Month and Older

  Age and Body Weight	Recommended Initial Dosage	Recommended Maximum Dosage	Frequency of Administration
  Adults (17 years and older)	150 mg/day	600 mg/day	2 or 3 divided doses
  Pediatric patients weighing 30 kg or more	2.5 mg/kg/day	10 mg/kg/day (not to exceed 600 mg/day)	2 or 3 divided doses
  Pediatric patients weighing less than 30 kg	3.5 mg/kg/day	14 mg/kg/day	1 month to less than 4 years of age: 3 divided doses 4 years of age and older : 2 or 3 divided doses

  Both the efficacy and adverse event profiles of pregabalin capsules have been shown to be dose-related.

  The effect of dose escalation rate on the tolerability of pregabalin capsules has not been formally studied.

  The efficacy of adjunctive pregabalin capsules in patients taking gabapentin has not been evaluated in controlled trials. Consequently, dosing recommendations for the use of pregabalin capsules with gabapentin cannot be offered.
  ,
  
  
  2.5 Management of Fibromyalgia in Adults

  The recommended dose of pregabalin capsules for fibromyalgia is 300 to 450 mg/day. Begin dosing at 75 mg two times a day (150 mg/day). The dose may be increased to 150 mg two times a day (300 mg/day) within 1 week based on efficacy and tolerability. Patients who do not experience sufficient benefit with 300 mg/day may be further increased to 225 mg two times a day (450 mg/day). Although pregabalin capsules were also studied at 600 mg/day, there is no evidence that this dose confers additional benefit and this dose was less well tolerated. In view of the dose-dependent adverse reactions, treatment with doses above 450 mg/day is not recommended

  [see Adverse Reactions (6.1)].
  ,
  
  
  2.6 Neuropathic Pain Associated with Spinal Cord Injury in Adults

  The recommended dose range of pregabalin capsules for the treatment of neuropathic pain associated with spinal cord injury is 150 to 600 mg/day. The recommended starting dose is 75 mg two times a day (150 mg/day). The dose may be increased to 150 mg two times a day (300 mg/day) within 1 week based on efficacy and tolerability. Patients who do not experience sufficient pain relief after 2 to 3 weeks of treatment with 150 mg two times a day and who tolerate pregabalin capsules may be treated with up to 300 mg two times a day

  [see Clinical Studies (14.5)].
  )
  
• Dosing recommendations:

• Dose should be adjusted in adult patients with reduced renal function. (
  
  
  2.7 Dosing for Adult Patients with Renal Impairment

  In view of dose-dependent adverse reactions and since pregabalin capsules are eliminated primarily by renal excretion, adjust the dose in adult patients with reduced renal function. The use of pregabalin capsules in pediatric patients with compromised renal function has not been studied.

  Base the dose adjustment in patients with renal impairment on creatinine clearance (CLcr), as indicated in Table 2. To use this dosing table, an estimate of the patient's CLcr in mL/min is needed. CLcr in mL/min may be estimated from serum creatinine (mg/dL) determination using the Cockcroft and Gault equation:

  

  Next, refer to the Dosage and Administration section to determine the recommended total daily dose based on indication, for a patient with normal renal function (CLcr greater than or equal to 60 mL/min). Then refer to Table 2 to determine the corresponding renal adjusted dose.

  (For example: A patient initiating pregabalin capsules therapy for postherpetic neuralgia with normal renal function (CLcr greater than or equal to 60 mL/min), receives a total daily dose of 150 mg/day pregabalin. Therefore, a renal impaired patient with a CLcr of 50 mL/min would receive a total daily dose of 75 mg/day pregabalin administered in two or three divided doses.)

  For patients undergoing hemodialysis, adjust the pregabalin daily dose based on renal function. In addition to the daily dose adjustment, administer a supplemental dose immediately following every 4-hour hemodialysis treatment (see Table 2).

  T able 2. Pregabalin Dosag e Adjustment Based on Renal Function

  Creatinine Clearance (CLcr) (mL/min)	Total Pregabalin Daily Dose (mg/day)*				Dose Regimen
  Greater than or equal to 60	150	300	450	600	BID or TID
  30-60	75	150	225	300	BID or TID
  15–30	25–50	75	100–150	150	QD or BID
  Less than 15	25	25–50	50–75	75	QD
  Supplementary dosage following hemodialysis (mg)†
  Patients on the 25 mg QD regimen: take one supplemental dose of 25 mg or 50 mg Patients on the 25–50 mg QD regimen: take one supplemental dose of 50 mg or 75 mg Patients on the 50–75 mg QD regimen: take one supplemental dose of 75 mg or 100 mg Patients on the 75 mg QD regimen: take one supplemental dose of 100 mg or 150 mg

  TID= Three divided doses; BID = Two divided doses; QD = Single daily dose.

  * Total daily dose (mg/day) should be divided as indicated by dose regimen to provide mg/dose.

  ^†Supplementary dose is a single additional dose.

  

  )
  

Capsules: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and 300 mg

[see

11 DESCRIPTION

Pregabalin USP is described chemically as (S)-3-(aminomethyl)-5-methylhexanoic acid. The molecular formula is C₈H₁₇NO₂and the molecular weight is 159.23. The chemical structure of pregabalin is:

Pregabalin USP is a white to off-white, crystalline solid with a pK_a1of 4.2 and a pK_a2of 10.6. It is sparingly soluble in water and freely soluble in both basic and acidic aqueous solutions. The log of the partition coefficient (n-octanol/0.05M phosphate buffer) at pH 7.4 is –1.35.

Pregabalin capsules are administered orally and are supplied as imprinted hard-shell capsules containing 25, 50, 75, 100, 150, 200, 225, and 300 mg of pregabalin, along with lactose monohydrate, pregelatinised starch, and talc as inactive ingredients.

The capsule shells contain gelatin and titanium dioxide. In addition, the orange capsule shells contain red iron oxide.

The imprinting ink contains shellac, black iron oxide, propylene glycol, ammonium solution concentrated and potassium hydroxide.

and

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Angioedema

Advise patients that pregabalin capsules may cause angioedema, with swelling of the face, mouth (lip, gum, tongue) and neck (larynx and pharynx) that can lead to life-threatening respiratory compromise. Instruct patients to discontinue pregabalin capsules and immediately seek medical care if they experience these symptoms

[see Warnings and Precautions (5.1)].

Hypersensitivity

Advise patients that pregabalin capsules has been associated with hypersensitivity reactions such as wheezing, dyspnea, rash, hives, and blisters. Instruct patients to discontinue pregabalin capsules and immediately seek medical care if they experience these symptoms

[see Warnings and Precautions (5.2)].

Suicidal Thinking and Behavior

Counsel patients, their caregivers, and families that AEDs, including pregabalin capsules, 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. Instruct patients, caregivers, and families to report behaviors of concern immediately to healthcare providers Also inform patients who plan to or have discontinued pregabalin capsules that suicidal thoughts and behavior can appear even after the drug is stopped

[see Warnings and Precautions (5.3)].

Respiratory Depression

Inform patients about the risk of respiratory depression. Include information that the risk is greatest for those using concomitant central nervous system (CNS) depressants (such as opioid analgesics) or in those with underlying respiratory impairment. Teach patients how to recognize respiratory depression and advise them to seek medical attention immediately if it occurs

[see Warnings and Precautions (5.5)].

Dizziness and Somnolence

Counsel patients that pregabalin capsules may cause dizziness, somnolence, blurred vision and other CNS signs and symptoms. Accordingly, advise patients not to drive, operate complex machinery, or engage in other hazardous activities until they have gained sufficient experience on pregabalin capsules to gauge whether or not it affects their mental, visual, and/or motor performance adversely

[see Warnings and Precautions (5.6)].

CNS Depressants

Inform patients who require concomitant treatment with central nervous system depressants such as opiates or benzodiazepines that they may experience additive CNS side effects, such as respiratory depression, somnolence, and dizziness

[see Warnings and Precautions and Drug Interactions (7)].

Advise patients to avoid consuming alcohol while taking pregabalin capsules, as pregabalin capsules may potentiate the impairments of motor skills and sedating effects of alcohol.

Adverse Reactions with Abrupt or Rapid Discontinuation

Advise patients to take pregabalin capsules as prescribed. Abrupt or rapid discontinuation may result in increased seizure frequency in patients with seizure disorders, and insomnia, nausea, headache, anxiety, hyperhidrosis, or diarrhea

[see Warnings and Precautions (5.4)].

Missed Dose

Counsel patients if they miss a dose, they should take it as soon as they remember. If it is almost time for the next dose, they should skip the missed dose and take the next dose at their regularly scheduled time. Instruct patients not to take two doses at the same time.

Weight Gain and Edema

Counsel patients that pregabalin capsules may cause edema and weight gain. Advise patients that concomitant treatment with pregabalin capsules and a thiazolidinedione antidiabetic agent may lead to an additive effect on edema and weight gain. For patients with preexisting cardiac conditions, this may increase the risk of heart failure

[see Warnings and Precautions ].

Ophthalmological Effects

Counsel patients that pregabalin capsules may cause visual disturbances. Inform patients that if changes in vision occur, they should notify their physician

[see Warnings and Precautions (5.10)].

Creatine Kinase Elevations

Instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever

[see Warnings and Precautions (5.11)].

Use in Pregnancy

Instruct patients to inform their healthcare provider if they are pregnant or intend to become pregnant during therapy, and to notify their physician if they are breast feeding or intend to breast feed during therapy

[see Use in Specific Populations (8.1)and (8.2)]

.

Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) 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 Use in Specific Populations (8.1)].

Lactation

Advise nursing mothers that breastfeeding is not recommended during treatment with pregabalin capsules

[see Use in Specific Populations (8.2)].

Male Fertility

Inform men being treated with pregabalin capsules who plan to father a child of the potential risk of male-mediated teratogenicity. In preclinical studies in rats, pregabalin was associated with an increased risk of male-mediated teratogenicity. The clinical significance of this finding is uncertain

[see Nonclinical Toxicology (13.1)and Use in Specific populations (8.3)]

.

Dermatopathy

Instruct diabetic patients to pay particular attention to skin integrity while being treated with pregabalin capsules and to inform their healthcare provider about any sores or skin problems. Some animals treated with pregabalin capsules developed skin ulcerations, although no increased incidence of skin lesions associated with pregabalin capsules was observed in clinical trials

[see Nonclinical Toxicology (13.2)].

Revised: 08/2025

Manufactured by:

V-Ensure Pharma Technologies Pvt. Ltd

Raigad, Maharashtra-410206, India.

Distributed by:

Creekwood Pharmaceuticals LLC.

Parsippany, NJ 07054.

PA1220107

]

• Lactation: Breastfeeding is not recommended. (
  
  
  8.2 Lactation

  Risk Summary

  Small amounts of pregabalin have been detected in the milk of lactating women. A pharmacokinetic study in lactating women detected pregabalin in breast milk at average steady state concentrations approximately 76% of those in maternal plasma. The estimated average daily infant dose of pregabalin from breast milk (assuming mean milk consumption of 150 mL/kg /day) was 0.31 mg/kg/day, which on a mg/kg basis would be approximately 7% of the maternal dose

  (see Data).

  The study did not evaluate the effects of pregabalin capsules on milk production or the effects of pregabalin capsules on the breastfed infant.

  Based on animal studies, there is a potential risk of tumorigenicity with pregabalin exposure via breast milk to the breastfed infant

  [see Nonclinical Toxicology (13.1)].

  Available clinical study data in patients greater than 12 years of age do not provide a clear conclusion about the potential risk of tumorigenicity with pregabalin

  [see Warnings and Precautions (5.9)].

  Because of the potential risk of tumorigenicity, breastfeeding is not recommended during treatment with pregabalin capsules.

  Data

  A pharmacokinetic study in ten lactating women, who were at least 12 weeks postpartum, evaluated the concentrations of pregabalin in plasma and breast milk. Pregabalin capsules 150 mg oral capsule was given every 12 hours (300 mg daily dose) for a total of four doses. Pregabalin was detected in breast milk at average steady-state concentrations approximately 76% of those in maternal plasma. The estimated average daily infant dose of pregabalin from breast milk (assuming mean milk consumption of 150 mL/kg/day) was 0.31 mg/kg/day, which on a mg/kg basis would be approximately 7% of the maternal dose. The study did not evaluate the effects of pregabalin capsules on milk production. Infants did not receive breast milk obtained during the dosing period, therefore, the effects of pregabalin capsules on the breast fed infant were not evaluated.
  )