Pregabalin 225 mg Capsule, 10-count — NDC 67877-468-33 (Billing 67877-0468-33)
This is a package of 10 capsules of Pregabalin 225 mg Capsule from Ascend Laboratories, LLC, marketed since Jul 2019 and currently FDA-listed.
Other active recalls for Pregabalin (different manufacturers) — 1 · tap to view
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 059401
- GCN: 25019
- HICL (First Databank): 026470
- AHFS class code: 28:12.28.00
- RxCUI (RxNorm): 483438
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Gabapentinoids class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
Pregabalin capsules, oral solution (liquid), and extended-release (long-acting) tablets are used to relieve neuropathic pain (pain from damaged nerves) that can occur in your arms, hands, fingers, legs, feet, or toes if you have diabetes and postherpetic neuralgia (PHN; the burning, stabbing pain or aches that may last for months or years after an attack of shingles). Pregabalin capsules and oral solution are also used to relieve neuropathic pain that can occur after a spinal cord injury and to treat fibromyalgia (a long-lasting condition that may cause pain, muscle stiffness and tenderness, t...
Read the full MedlinePlus article ↗- It treats nerve pain from diabetes and from shingles. Some products, like Lyrica and pregabalin capsules and oral solution, are also used for fibromyalgia, spinal cord injury nerve...
- Yes for the capsules and oral solution, with or without food. The extended-release tablets are taken once a day after your evening meal and swallowed whole. Do not crush, split or...
- If you miss the dose after your evening meal, take your usual dose at bedtime with a snack. If you miss that too, take it after a morning meal. If you miss that as well, just take...
- What happens if I miss a dose of pregabalin extended-release?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Pregabalin — tap one for details:
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $0.1702 | $1.70 / 10 capsules |
Where does this data come from?
- CMS NADAC weekly file
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · refreshed Oct 3, 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Marketing end | Status |
|---|---|---|---|---|---|---|
| 67877-0468-05 67877-468-05 | 500 CAPSULE in 1 BOTTLE | $0.0635 / ea | $31.75 | 2019-07-21 | — | Active |
| 67877-0468-30 67877-468-30 | 30 CAPSULE in 1 BOTTLE | — | — | 2019-07-21 | — | Active |
| 67877-0468-33 You're viewing this | 1 BLISTER PACK in 1 CARTON / 10 CAPSULE in 1 BLISTER PACK | — | — | 2019-07-21 | — | Active |
| 67877-0468-38 67877-468-38 | 10 BLISTER PACK in 1 CARTON / 10 CAPSULE in 1 BLISTER PACK | — | — | 2019-07-21 | — | Active |
| 67877-0468-90 67877-468-90 Main listing | 90 CAPSULE in 1 BOTTLE | $0.0635 / ea | $5.71 | 2019-07-21 | — | Active |
This pack shows little to no recent Medicaid volume — the 90 capsules pack carries most fills. See all packs ↓
Pack size FAQ
What quantity is in this package?
How does this package differ from NDC 67877-0468-30?
What NDC number is used to bill for this package of Pregabalin 225 mg Capsule?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Pregabalin 225 mg 00904-7004-04 | Major | 30 capsules | $0.063 | AB | Availability likely | — |
| Pregabalin 225 mg 31722-0616-05 | Camber | 500 capsules | $0.063 | AB | Availability likely | — |
| Pregabalin 225 mg 43547-0512-09 | Solco | 90 capsules | $0.063 | AB | Availability likely | — |
| Pregabalin 225 mg 50228-0651-05 | ScieGen | 500 capsules | $0.063 | AB | Availability likely | — |
| Pregabalin 225 mg 69238-1316-09 | Amneal | 90 capsules | $0.063 | AB | Availability likely | — |
| Pregabalin 225 mg 69367-0330-09 | Westminster | 90 capsules | $0.063 | AB | Availability likely | — |
| Pregabalin 225 mg 69097-0961-05 | Cipla | 90 capsules | $0.086 | AB | FDA listed | — |
| Lyrica 225 mg 58151-0243-77 | Viatris | 90 capsules | $9.684 | AB | Availability likely | — |
| Pregabalin 225 mg 13668-0364-01 | Torrent | 100 capsules | — | AB | FDA listed | — |
| pregabalin 225 mg 14445-0127-90 | Indoco | 90 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 25000-0185-07 | MARKSANS | 90 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 27808-0240-01 | Tris | 90 capsules | — | AB | FDA listed | — |
| Pregablin 225 mg 33342-0171-10 | Macleods | 90 capsules | — | — | FDA listed | — |
| pregabalin 225 mg 43598-0297-05 | Dr.Reddys | 500 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 46708-0125-10 | Alembic | 100 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 47335-0692-08 | Sun | 100 capsules | — | — | FDA listed | — |
| Pregabalin 225 mg 50228-0356-05 | ScieGen | 500 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 51407-0580-90 | Golden | 90 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 60219-1316-09 | Amneal | 90 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 62332-0125-10 | Alembic | 100 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 63629-8239-01 | Bryant | 30 capsules | — | AB | Discontinued | — |
| Pregabalin 225 mg 64980-0416-01 | Rising | 100 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 65862-0764-05 | Aurobindo | 500 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mgthis 67877-0468-33 | Ascend | 10 capsules | — | AB | FDA listed | — |
| PREGABALIN capsules, CV 225 mg 69097-0684-02 | Cipla | 30 capsules | — | — | Discontinued | — |
| Pregabalin 225 mg 69367-0430-05 | Westminster | 500 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 70518-4569-00 | REMEDYREPACK | 90 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 71205-0875-00 | Proficient | 100 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 71209-0038-04 | Cadila | 90 capsules | — | — | FDA listed | — |
| Pregabalin 225 mg 71335-1744-01 | Bryant | 30 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 71335-9671-01 | Bryant | 30 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 71610-0319-53 | Aphena | 60 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 71610-0760-46 | Aphena | 56 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 71610-0946-30 | Aphena | 30 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 71610-0947-30 | Aphena | 30 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 71610-0995-30 | Aphena | 30 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 72162-1547-09 | Bryant | 90 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 72189-0045-30 | Direct_Rx | 30 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 72189-0328-60 | Direct | 60 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 72205-0017-06 | Novadoz | 1000 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 72658-0813-01 | Eskayef | 60 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 73190-0059-50 | AvKARE | 500 capsules | — | AB | Discontinued | — |
| Pregabalin 225 mg 76282-0574-05 | Exelan | 500 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 76420-0101-30 | Asclemed | 30 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 76420-0123-30 | Asclemed | 30 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 80425-0399-01 | Advanced | 30 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 82619-0128-01 | Creekwood | 90 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 82804-0949-00 | Proficient | 100 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 82968-0012-01 | FOURRTS | 90 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 29300-0445-19 | Unichem | 90 capsules | — | AB | FDA listed | — |
| Pregabalin 225 mg 58118-0764-08 | Clinical | 30 capsules | — | AB | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Oct 3, 2026
- CMS NADAC weekly file
Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
- FDA Orange Book · refreshed Oct 3, 2026
What it looks like
Where does this data come from?
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 1K09F3G675
Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
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UNII EX438O2MRT
Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
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UNII XM0M87F357
A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
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UNII 2G86QN327L
Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
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UNII WZH3C48M4T
Potassium hydroxide is a strong alkaline chemical used in medicines to adjust and maintain the pH level of liquid formulations, helping keep the product stable and the active ingredients effective.
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UNII 6DC9Q167V3
Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
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UNII 46N107B71O
Shellac is a natural resin secreted by the lac beetle. It's used as a coating on tablets and capsules to control how quickly the medicine dissolves and to improve appearance and stability.
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UNII 368GB5141J
A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
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UNII O8232NY3SJ
A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
11 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 1, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
Manufacturer & labeler
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Pregabalin 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 Pregabalin is indicated for: Neuropathic pain associated with diabetic peripheral neuropathy (DPN) ( 1 ) Postherpetic neuralgia (PHN) ( 1 ) Adjunctive therapy for the treatment of partial-onset seizures in patients 1 month of age and older ( 1 ) Fibromyalgia ( 1 ) Neuropathic pain associated with spinal cord injury ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION 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. ( 2.2, 2.3, 2.4, 2.5, 2.6 ) Dosing recommendations: INDICATION Dosing Regimen Maximum Dose DPN Pain ( 2.2 ) 3 divided doses per day 300 mg/day within 1 week.
PHN ( 2.3 ) 2 or 3 divided doses per day 300 mg/day within 1 week. Maximum dose of 600 mg/day. Adjunctive Therapy for Partial-Onset Seizures in Pediatric and Adult Patients Weighing 30 kg or More ( 2.4 ) 2 or 3 divided doses per day Maximum dose of 600 mg/day.
Adjunctive Therapy for Partial-Onset Seizures in Pediatric Patients Weighing Less than 30 kg ( 2.4 ) 1 month to less than 4 years: 3 divided doses per day 4 years and older : 2 or 3 divided doses per day 14mg/kg/day. Fibromyalgia ( 2.5 ) 2 divided doses per day 300 mg/day within 1 week. Maximum dose of 450 mg/day.
Neuropathic Pain Associated with Spinal Cord Injury ( 2.6 ) 2 divided doses per day 300 mg/day within 1 week. Maximum dose of 600 mg/day. Dose should be adjusted in adult patients with reduced renal function.
( 2.7 )
2.1Important Administration Instructions Pregabalin is given orally with or without food. When discontinuing pregabalin, taper gradually over a minimum of 1 week [ see Warnings and Precautions ( 5.4 ) ] . Because pregabalin is eliminated primarily by renal excretion, adjust the dose in adult patients with reduced renal function [ see Dosage and Administration ( 2.7 ) ].
2.2Neuropathic Pain Associated with Diabetic Peripheral Neuropathy in Adults The maximum recommended dose of pregabalin is 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 was 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 )].
2.3Postherpetic Neuralgia in Adults The recommended dose of pregabalin is 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, 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 )].
2.4Adjunctive 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 tha… [Excerpted — this section continues on DailyMed.]
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Capsules: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and 300 mg. [see Description (11) and How Supplied/Storage and Handling (16) ]. Capsules: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and 300 mg. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Pregabalin is contraindicated in patients with known hypersensitivity to pregabalin or any of its components. Angioedema and hypersensitivity reactions have occurred in patients receiving pregabalin therapy [see Warnings and Precautions ( 5.2 )]. Known hypersensitivity to pregabalin or any of its components. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Angioedema (e.g., swelling of the throat, head, and neck) can occur, and may be associated with life-threatening respiratory compromise requiring emergency treatment. Discontinue pregabalin immediately in these cases. ( 5.1 ) Hypersensitivity reactions (e.g., hives, dyspnea, and wheezing) can occur.
Discontinue pregabalin immediately in these patients. ( 5.2 ) Antiepileptic drugs, including pregabalin, the active ingredient in pregabalin capsules, increase the risk of suicidal thoughts or behavior. ( 5.3 ) Abrupt or rapid discontinuation may increase the risk for seizures.
Withdrawal symptoms or suicidal behavior and ideation have been observed after discontinuation. Taper pregabalin gradually over a minimum of 1 week. ( 5.4 ) Respiratory depression: May occur with pregabalin, when used with concomitant CNS depressants or in the setting of underlying respiratory impairment.
Monitor patients and adjust dosage as appropriate. ( 5.5 ) Pregabalin may cause dizziness and somnolence and impair patients’ ability to drive or operate machinery. ( 5.6 ) Pregabalin may cause peripheral edema.
Exercise caution when co-administering pregabalin and thiazolidinedione antidiabetic agents. ( 5.7 )
5.1Angioedema There have been postmarketing reports of angioedema in patients during initial and chronic treatment with pregabalin. Specific symptoms included swelling of the face, mouth (tongue, lips, and gums), and neck (throat and larynx). There were reports of life-threatening angioedema with respiratory compromise requiring emergency treatment.
Discontinue pregabalin immediately in patients with these symptoms. Exercise caution when prescribing pregabalin to patients who have had a previous episode of angioedema. In addition, patients who are taking other drugs associated with angioedema (e.g., angiotensin converting enzyme inhibitors [ACE-inhibitors]) may be at increased risk of developing angioedema.
5.2Hypersensitivity There have been postmarketing reports of hypersensitivity in patients shortly after initiation of treatment with pregabalin. Adverse reactions included skin redness, blisters, hives, rash, dyspnea, and wheezing. Discontinue pregabalin immediately in patients with these symptoms.
5.3Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including pregabalin, the active ingredient in pregabalin capsules, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Suicidal behavior and ideation have also been reported in patients after discontinuation of pregabalin [see Warnings and Precautions ( 5.4 )]. Monitor patients treated with any AED for any indication 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.… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Angioedema [see Warnings and Precautions ( 5.1 )] Hypersensitivity [see Warnings and Precautions ( 5.2 )] Suicidal Behavior and Ideation [see Warnings and Precautions ( 5.3 )] Increased Risk of Adverse Reactions with Abrupt or Rapid Discontinuation [see Warnings and Precautions ( 5.4 )] Respiratory Depression [see Warnings and Precautions ( 5.5 )] Dizziness and Somnolence [see Warnings and Precautions ( 5.6 )] Peripheral Edema [see Warnings and Precautions ( 5.7 )] Weight Gain [see Warnings and Precautions ( 5.8 )] Tumorigenic Potential [see Warnings and Precautions ( 5.9 )] Ophthalmological Effects [see Warnings and Precautions ( 5.10 )] Creatine Kinase Elevations [see Warnings and Precautions ( 5.11 )] Decreased Platelet Count [see Warnings and Precautions ( 5.12 )] PR Interval Prolongation [see Warnings and Precautions ( 5.13 )] Most common adverse reactions (greater than or equal to 5% and twice placebo) in adults are dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, and thinking abnormal (primarily difficulty with concentration/attention).
( 6.1 ) Most common adverse reactions (greater than or equal to 5% and twice placebo) in pediatric patients for the treatment of partial-onset seizures are increased weight and increased appetite. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-272-7901 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical 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. In all controlled and uncontrolled trials across various patient populations during the premarketing development of pregabalin, more than 10,000 patients have received pregabalin. Approximately 5,000 patients were treated for 6 months or more, over 3,100 patients were treated for 1 year or longer, and over 1,400 patients were treated for at least 2 years.
Adverse Reactions Most Commonly Leading to Discontinuation in All Premarketing Controlled Clinical Studies In premarketing controlled trials of all adult populations combined, 14% of patients treated with pregabalin and 7% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin treatment group, the adverse reactions most frequently leading to discontinuation were dizziness (4%) and somnolence (4%). In the placebo group, 1% of patients withdrew due to dizziness and less than 1% withdrew due to somnolence.
Other adverse reactions that led to discontinuation from controlled trials more frequently in the pregabalin group compared to the placebo group were ataxia, confusion, asthenia, thinking abnormal, blurred vision, incoordination, and peripheral edema (1% each). Most Common Adverse Reactions in All Controlled Clinical Studies in Adults In premarketing controlled trials of all adult patient populations combined (including DPN, PHN, and adult patients with partial-onset seizures), dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, and "thinking abnormal" (primarily difficulty with concentration/attention) were more commonly reported by subjects treated with pregabalin than by subjects treated with placebo (greater than or equal to 5% and twice the rate of that seen in placebo).
Controlled Studies with Neuropathic Pain Associated with Diabetic Peripheral Neuropathy Adverse Reactions Leading to Discontinuation In clinical trials in adults with neuropathic pain associated with diabetic peripheral neuropathy, 9% of patients treated with pregabalin and 4% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin treatment group, the most common reasons for discontinuation due to adverse re… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Since pregabalin is predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans (less than 2% of a dose recovered in urine as metabolites), and does not bind to plasma proteins, its pharmacokinetics are unlikely to be affected by other agents through metabolic interactions or protein binding displacement. In vitro and in vivo studies showed that pregabalin is unlikely to be involved in significant pharmacokinetic drug interactions. Specifically, there are no pharmacokinetic interactions between pregabalin and the following antiepileptic drugs: carbamazepine, valproic acid, lamotrigine, phenytoin, phenobarbital, and topiramate.
Important pharmacokinetic interactions would also not be expected to occur between pregabalin and commonly used antiepileptic drugs [see Clinical Pharmacology (12)] . Pharmacodynamics Multiple oral doses of pregabalin were co-administered with oxycodone, lorazepam, or ethanol. Although no pharmacokinetic interactions were seen, additive effects on cognitive and gross motor functioning were seen when pregabalin was co-administered with these drugs.
No clinically important effects on respiration were seen.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Breastfeeding is not recommended. ( 8.2 )
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to pregabalin during pregnancy. To provide information regarding the effects of in utero exposure to pregabalin, physicians are advised to recommend that pregnant patients taking pregabalin 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/ . Risk Summary Observational studies on the use of pregabalin during pregnancy suggest a possible small increase in the rate of overall major birth defects, but there was no consistent or specific pattern of major birth defects identified (see Data) . Available postmarketing data on miscarriage and other maternal, fetal, and long term developmental adverse effects were insufficient to identify risk associated with pregabalin.
Postmarketing data suggest that extended gabapentinoid use with opioids close to delivery may increase the risk of neonatal withdrawal versus opioids alone (see Clinical Considerations). There are no comparative epidemiologic studies evaluating this association. Therefore, it is not known whether exposure to pregabalin alone late in pregnancy may cause withdrawal signs and symptoms.
In animal reproduction studies, increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity, including skeletal malformations, retarded ossification, and decreased fetal body weight were observed in the offspring of rats and rabbits given pregabalin orally during organogenesis, at doses that produced plasma pregabalin exposures (AUC) greater than or equal to 16 times human exposure at the maximum recommended dose (MRD) of 600 mg/day ( see Data) . In an animal development study, lethality, growth retardation, and nervous and reproductive system functional impairment were observed in the offspring of rats given pregabalin during gestation and lactation.
The no-effect dose for developmental toxicity was approximately twice the human exposure at MRD. The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Neonatal withdrawal syndrome has been reported in newborns exposed to gabapentinoids in utero for an extended period of time when also exposed to opioids close to delivery. Neonatal withdrawal signs and symptoms reported have included tachypnea, vomiting, diarrhea, hypertonia, irritability, sneezing, poor feeding, hyperactivity, abnormal sleep pattern, and tremor.
Reported signs and symptoms that may also be related to withdrawal include tongue thrusting, wandering eye movements while awake, back arching, and continuous extremity movements. Observe neonates exposed to pregabalin and opioids for signs and symptoms of neonatal withdrawal and manage accordingly. Data Human Data One database study, which included over 2,700 pregnancies exposed to pregabalin (monotherapy) during the first trimester compared to 3,063,251 pregnancies unexposed to antiepileptics demonstrated prevalence ratios for major malformations overall of 1.14 (CI 95% 0.96-1.35) for pregabalin, 1.29 (CI 95% 1.01-1.65) for lamotrigine, 1.39 (CI 95% 1.07-1.82) for duloxetine, and 1.24 (CI 95% 1.00-1.54) for exposure to either lamotrigine or duloxetine.
Important study limitations include uncertainty of whether women who filled a prescription took the medication and inability to a… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to pregabalin during pregnancy. To provide information regarding the effects of in utero exposure to pregabalin, physicians are advised to recommend that pregnant patients taking pregabalin 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/ . Risk Summary Observational studies on the use of pregabalin during pregnancy suggest a possible small increase in the rate of overall major birth defects, but there was no consistent or specific pattern of major birth defects identified (see Data) . Available postmarketing data on miscarriage and other maternal, fetal, and long term developmental adverse effects were insufficient to identify risk associated with pregabalin.
Postmarketing data suggest that extended gabapentinoid use with opioids close to delivery may increase the risk of neonatal withdrawal versus opioids alone (see Clinical Considerations). There are no comparative epidemiologic studies evaluating this association. Therefore, it is not known whether exposure to pregabalin alone late in pregnancy may cause withdrawal signs and symptoms.
In animal reproduction studies, increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity, including skeletal malformations, retarded ossification, and decreased fetal body weight were observed in the offspring of rats and rabbits given pregabalin orally during organogenesis, at doses that produced plasma pregabalin exposures (AUC) greater than or equal to 16 times human exposure at the maximum recommended dose (MRD) of 600 mg/day ( see Data) . In an animal development study, lethality, growth retardation, and nervous and reproductive system functional impairment were observed in the offspring of rats given pregabalin during gestation and lactation.
The no-effect dose for developmental toxicity was approximately twice the human exposure at MRD. The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Neonatal withdrawal syndrome has been reported in newborns exposed to gabapentinoids in utero for an extended period of time when also exposed to opioids close to delivery. Neonatal withdrawal signs and symptoms reported have included tachypnea, vomiting, diarrhea, hypertonia, irritability, sneezing, poor feeding, hyperactivity, abnormal sleep pattern, and tremor.
Reported signs and symptoms that may also be related to withdrawal include tongue thrusting, wandering eye movements while awake, back arching, and continuous extremity movements. Observe neonates exposed to pregabalin and opioids for signs and symptoms of neonatal withdrawal and manage accordingly. Data Human Data One database study, which included over 2,700 pregnancies exposed to pregabalin (monotherapy) during the first trimester compared to 3,063,251 pregnancies unexposed to antiepileptics demonstrated prevalence ratios for major malformations overall of 1.14 (CI 95% 0.96-1.35) for pregabalin, 1.29 (CI 95% 1.01-1.65) for lamotrigine, 1.39 (CI 95% 1.07-1.82) for duloxetine, and 1.24 (CI 95% 1.00-1.54) for exposure to either lamotrigine or duloxetine.
Important study limitations include uncertainty of whether women who filled a prescription took the medication and inability to adequately control for the underlying disease and other potential confounders. A pub… [Excerpted — this section continues on DailyMed.]
🧒 Pediatric Use ▾
8.4Pediatric Use Neuropathic Pain Associated with Diabetic Peripheral Neuropathy, Postherpetic Neuralgia, and Neuropathic Pain Associated with Spinal Cord Injury Safety and effectiveness in pediatric patients have not been established. Fibromyalgia Safety and effectiveness in pediatric patients have not been established. A 15-week, placebo-controlled trial was conducted with 107 pediatric patients with fibromyalgia, ages 12 through 17 years, at pregabalin total daily doses of 75 to 450 mg per day.
The primary efficacy endpoint of change from baseline to Week 15 in mean pain intensity (derived from an 11-point numeric rating scale) showed numerically greater improvement for the pregabalin-treated patients compared to placebo-treated patients, but did not reach statistical significance. The most frequently observed adverse reactions in the clinical trial included dizziness, nausea, headache, weight increased, and fatigue. The overall safety profile in adolescents was similar to that observed in adults with fibromyalgia.
Adjunctive Therapy for Partial-Onset Seizures Safety and effectiveness in pediatric patients below the age of 1 month have not been established. 4 to Less Than 17 Years of Age with Partial-Onset Seizures The safety and effectiveness of pregabalin as adjunctive treatment for partial-onset seizures in pediatric patients 4 to less than 17 years of age have been established in a 12-week, double-blind, placebo-controlled study (n=295) [see Clinical Studies (14.3)] . Patients treated with pregabalin 10 mg/kg/day had, on average, a 21.0% greater reduction in partial-onset seizures than patients treated with placebo (p=0.0185).
Patients treated with pregabalin 2.5 mg/kg/day had, on average, a 10.5% greater reduction in partial-onset seizures than patients treated with placebo, but the difference was not statistically significant (p=0.2577). Responder rates (50% or greater reduction in partial-onset seizure frequency) were a key secondary efficacy parameter and showed numerical improvement with pregabalin compared with placebo: the responder rates were 40.6%, 29.1%, and 22.6%, for pregabalin 10 mg/kg/day, pregabalin 2.5 mg/kg/day, and placebo, respectively.
The most common adverse reactions (≥5%) with pregabalin in this study were somnolence, weight increased, and increased appetite [see Adverse Reactions (6.1)]. The use of pregabalin 2.5 mg/kg/day in pediatric patients is further supported by evidence from adequate and well-controlled studies in adults with partial-onset seizures and pharmacokinetic data from adult and pediatric patients [see Clinical Pharmacology (12.3)]. 1 Month to Less than 4 Years of Age with Partial-Onset Seizures The safety and effectiveness of pregabalin as adjunctive treatment for partial-onset seizures in pediatric patients 1 month to less than 4 years of age have been established in a 14-day double-blind, placebo-controlled study (N=175) [see Clinical Studies (14.3)] .
The youngest subject evaluated was 3 months of age; use in patients 1 month to less than 3 months of age is supported by additional pharmacokinetic analyses. Patients treated with pregabalin 14 mg/kg/day had, on average, 43.9% greater reduction in partial-onset seizures than patients treated with placebo (p=0.0223). In addition, pediatric patients treated with pregabalin 14 mg/kg/day showed numerical improvement in responder rates (≥50% reduction in partial-onset seizure frequency) compared with placebo (53.6% versus 41.5%).
Patients treated with pregabalin 7 mg/kg/day did not show improvement relative to placebo for either endpoint. The most common dose-related adverse reactions ( > 5%) with pregabalin in this study were somnolence, pneumonia, and viral infection [see Adverse Reactions ( 6.1 )]. Juvenile Animal Data In studies in which pregabalin (50 to 500 mg/kg) was orally administered to young rats from early in the postnatal period (Postnatal Day 7) through sexual maturity, neurobehavioral abnormalities (deficits in learnin… [Excerpted — this section continues on DailyMed.]
🧓 Geriatric Use ▾
8.5Geriatric Use In controlled clinical studies of pregabalin in neuropathic pain associated with diabetic peripheral neuropathy, 246 patients were 65 to 74 years of age, and 73 patients were 75 years of age or older. In controlled clinical studies of pregabalin in neuropathic pain associated with postherpetic neuralgia, 282 patients were 65 to 74 years of age, and 379 patients were 75 years of age or older. In controlled clinical studies of pregabalin in epilepsy, there were only 10 patients 65 to 74 years of age, and 2 patients who were 75 years of age or older.
No overall differences in safety and efficacy were observed between these patients and younger patients. In controlled clinical studies of pregabalin in fibromyalgia, 106 patients were 65 years of age or older. Although the adverse reaction profile was similar between the two age groups, the following neurological adverse reactions were more frequent in patients 65 years of age or older: dizziness, vision blurred, balance disorder, tremor, confusional state, coordination abnormal, and lethargy.
Pregabalin is known to be substantially excreted by the kidney, and the risk of toxic reactions to pregabalin may be greater in patients with impaired renal function. Because pregabalin is eliminated primarily by renal excretion, adjust the dose for elderly patients with renal impairment [see Dosage and Administration ( 2.7 )].
🆘 Overdosage ▾
10 OVERDOSAGE Signs, Symptoms and Laboratory Findings of Acute Overdosage in Humans In the postmarketing experience, the most commonly reported adverse events observed with pregabalin when taken in overdose include reduced consciousness, depression/anxiety, confusional state, agitation, and restlessness. Seizures and heart block have also been reported. Deaths have been reported in the setting of lone pregabalin overdose and in combination with other CNS depressants.
Treatment or Management of Overdose There is no specific antidote for overdose with pregabalin. If indicated, elimination of unabsorbed drug may be attempted by emesis or gastric lavage; observe usual precautions to maintain the airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of the clinical status of the patient.
Contact a Certified Poison Control Center for up-to-date information on the management of overdose with pregabalin. Pregabalin can be removed by hemodialysis. Standard hemodialysis procedures result in significant clearance of pregabalin (approximately 50% in 4 hours).
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Pregabalin binds with high affinity to the alpha 2 -delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues. Although the mechanism of action of pregabalin has not been fully elucidated, results with genetically modified mice and with compounds structurally related to pregabalin (such as gabapentin) suggest that binding to the alpha 2 -delta subunit may be involved in pregabalin’s anti-nociceptive and antiseizure effects in animals. In animal models of nerve damage, pregabalin has been shown to reduce calcium-dependent release of pro-nociceptive neurotransmitters in the spinal cord, possibly by disrupting alpha 2 -delta containing-calcium channel trafficking and/or reducing calcium currents.
Evidence from other animal models of nerve damage and persistent pain suggest the anti-nociceptive activities of pregabalin may also be mediated through interactions with descending noradrenergic and serotonergic pathways originating from the brainstem that modulate pain transmission in the spinal cord. While pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA A , GABA B , or benzodiazepine receptors, does not augment GABA A responses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on GABA uptake or degradation.
However, in cultured neurons prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport. Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.
12.3Pharmacokinetics Pregabalin is well absorbed after oral administration, is eliminated largely by renal excretion, and has an elimination half-life of about 6 hours. Absorption and Distribution Following oral administration of pregabalin capsules under fasting conditions, peak plasma concentrations occur within 1.5 hours. Pregabalin oral bioavailability is greater than or equal to 90% and is independent of dose.
Following single-(25 to 300 mg) and multiple-dose (75 to 900 mg/day) administration, maximum plasma concentrations (C max ) and area under the plasma concentration-time curve (AUC) values increase linearly. Following repeated administration, steady state is achieved within 24 to 48 hours. Multiple-dose pharmacokinetics can be predicted from single-dose data.
The rate of pregabalin absorption is decreased when given with food, resulting in a decrease in C max of approximately 25% to 30% and an increase in T max to approximately 3 hours. However, administration of pregabalin with food has no clinically relevant effect on the total absorption of pregabalin. Therefore, pregabalin can be taken with or without food.
Pregabalin does not bind to plasma proteins. The apparent volume of distribution of pregabalin following oral administration is approximately
0.5L/kg. Pregabalin is a substrate for system L transporter which is responsible for the transport of large amino acids across the blood brain barrier. Although there are no data in humans, pregabalin has been shown to cross the blood brain barrier in mice, rats, and monkeys.
In addition, pregabalin has been shown to cross the placenta in rats and is present in the milk of lactating rats. Metabolism and Elimination Pregabalin undergoes negligible metabolism in humans. Following a dose of radiolabeled pregabalin, approximately 90% of the administered dose was recovered in the urine as unchanged pregabalin.
The N-methylated derivative of pregabalin, the major metabolite of pregabalin found in urine, accounted for 0.9% of the dose. In preclinical studies, pregabalin (S-enantiomer) did not undergo racemization to the R-enantiomer in mice, rats, rabbit… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action Pregabalin binds with high affinity to the alpha 2 -delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues. Although the mechanism of action of pregabalin has not been fully elucidated, results with genetically modified mice and with compounds structurally related to pregabalin (such as gabapentin) suggest that binding to the alpha 2 -delta subunit may be involved in pregabalin’s anti-nociceptive and antiseizure effects in animals. In animal models of nerve damage, pregabalin has been shown to reduce calcium-dependent release of pro-nociceptive neurotransmitters in the spinal cord, possibly by disrupting alpha 2 -delta containing-calcium channel trafficking and/or reducing calcium currents.
Evidence from other animal models of nerve damage and persistent pain suggest the anti-nociceptive activities of pregabalin may also be mediated through interactions with descending noradrenergic and serotonergic pathways originating from the brainstem that modulate pain transmission in the spinal cord. While pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA A , GABA B , or benzodiazepine receptors, does not augment GABA A responses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on GABA uptake or degradation.
However, in cultured neurons prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport. Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING 25 mg capsules: White to off white powder filled in size"4" hard gelatin capsules, white opaque cap imprinted with 'A007' with black ink and white opaque body imprinted with "PREG 25"with black ink, available in: Bottles of 30: NDC-67877-462-30 Bottles of 90: NDC-67877-462-90 Bottles of 500: NDC-67877-462-05 Unit-Dose Blister Packages of 100 (10×10): NDC-67877-462-38 Unit-Dose Blister Pack of 10 (1x10): NDC-67877-462-33 50 mg capsules: White to off white powder filled in size"3" hard gelatin capsules, white opaque cap imprinted with 'A008' with black ink and white opaque body imprinted with "PREG 50"with black ink, available in: Bottles of 30: NDC-67877-463-30 Bottles of 90: NDC-67877-463-90 Bottles of 500: NDC-67877-463-05 Unit-Dose Blister Packages of 100 (10×10): NDC-67877-463-38 Unit-Dose Blister Pack of 10 (1x10): NDC-67877-463-33 75 mg capsules: White / orange hard gelatin capsules, imprinted with black ink ‘A009’ on the cap and “PREG 75” on the body; available in: Bottles of 30: NDC-67877-464-30 Bottles of 90: NDC-67877-464-90 Bottles of 500: NDC-67877-464-05 Unit-Dose Blister Packages of 100(10×10): NDC-67877-464-38 Unit-Dose Blister Pack of 10 (1x10): NDC-67877-464-33 100 mg capsules: Orange hard gelatin capsules, imprinted with black ink ‘A010’ on the cap and “PREG 100” on the body; available in: Bottles of 30: NDC-67877-465-30 Bottles of 90: NDC-67877-465-90 Bottles of 500: NDC-67877-465-05 Unit-Dose Blister Packages of 100(10×10): NDC-67877-465-38 Unit-Dose Blister Pack of 10 (1x10): NDC-67877-465-33 150 mg capsules: White hard gelatin capsules, imprinted with black ink ‘A011’ on the cap and “PREG 150” on the body; available in: Bottles of 30: NDC-67877-466-30 Bottles of 90: NDC-67877-466-90 Bottles of 500: NDC-67877-466-05 Unit-Dose Blister Packages of 100(10×10): NDC-67877-466-38 Unit-Dose Blister Pack of 10 (1x10): NDC-67877-466-33 200 mg capsules: Light orange hard gelatin capsules, imprinted with black ink ‘A012’ on the cap and “PREG 200” on the body; available in: Bottles of 30: NDC-67877-467-30 Bottles of 90: NDC-67877-467-90 Bottles of 500: NDC-67877-467-05 Unit-Dose Blister Packages of 100(10×10): NDC-67877-467-38 Unit-Dose Blister Pack of 10 (1x10): NDC-67877-467-33 225 mg capsules : White / light orange hard gelatin capsules, imprinted with black ink ‘A013’ and “PREG 225” on the body; available in: Bottles of 30: NDC-67877-468-30 Bottles of 90: NDC-67877-468-90 Bottles of 500: NDC-67877-468-05 Unit-Dose Blister Packages of 100(10×10): NDC-67877-468-38 Unit-Dose Blister Pack of 10 (1x10): NDC-67877-468-33 300 mg capsules: White / light orange hard gelatin capsules, imprinted with black ink ‘A014’ and “PREG 300” on the body; available in: Bottles of 30: NDC-67877-469-30 Bottles of 90: NDC-67877-469-90 Bottles of 500: NDC-67877-469-05 Unit-Dose Blister Packages of 100(10×10): NDC-67877-469-38 Unit-Dose Blister Pack of 10 (1x10): NDC-67877-469-33 Storage and Handling Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature].
📋 Description ▾
11 DESCRIPTION Pregabalin is described chemically as ( S )-3-(aminomethyl)-5-methylhexanoic acid. The molecular formula is C 8 H 17 NO 2 and the molecular weight is 159.23. The chemical structure of pregabalin is: Pregabalin is a white to off-white, crystalline solid with a pK a1 of 4.2 and a pK a2 of 10.6.
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 – 1.35. Pregabalin Capsules are administered orally and are supplied as imprinted hard-shell capsules containing 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and 300 mg of pregabalin, along with pregelatinized starch, and talc as inactive ingredients.
The capsule shells contain gelatin, sodium lauryl sulfate and titanium dioxide. In addition, the orange capsule shells (75 mg, 100 mg, 200 mg, 225 mg and 300 mg) contain red iron oxide, yellow iron oxide. The imprinting ink contains black iron oxide, potassium hydroxide, propylene glycol and shellac.
Pregabalin structure
💬 Information for Patients ▾
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 ( 5.5 , 5.6 ) and Drug Interactions ( 7 )].
Advise patients to avoid consuming alcohol while taking pregabalin capsules, as pregabalin capsules may potentiate the impairment 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 ( 5.7 , 5.8 )].
Ophthalmological Effects Counsel patients that pregabalin… [Excerpted — this section continues on DailyMed.]
💬 Medication Guide ▾
MEDICATION GUIDE PREGABALIN (pree gab' a lin) capsules, CV Read this Medication Guide before you start taking pregabalin 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.
If you have any questions about pregabalin capsules, ask your healthcare provider or pharmacist. What is the most important information I should know about pregabalin capsules? Pregabalin capsules may cause serious side effects including: serious, even life-threatening, allergic reactions suicidal thoughts or actions swelling of your hands, legs and feet dizziness and sleepiness serious breathing problems These serious side effects are described below: Serious, even life-threatening, allergic reactions.
Stop taking pregabalin capsules and call your healthcare provider right away if you have any of these signs of a serious allergic reaction: o swelling of your face, mouth, lips, gums, tongue, throat or neck o trouble breathing o rash, hives (raised bumps) or blisters Like other antiepileptic drugs, pregabalin capsules may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.This can happen while you take pregabalin capsules or after stopping. 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 If you have suicidal thoughts or actions, do not stop pregabalin capsules without first talking to a healthcare provider. o Stopping pregabalin capsules suddenly can cause serious problems. o 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. 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. Serious breathing problems can occur when pregabalin capsules is taken with other medicines that can cause severe sleepiness or decreased awareness, or when it is taken by someone who already has breathing problems.
Watch for increased sleepiness or decreased breathing when starting pregabalin capsules or when the dose is increased. Get help right away if breathing problems occur. Swelling of your hands, legs and feet .
This swelling can be a serious problem for people with heart problems. Dizziness and sleepiness. Do not drive a car, work with machines, or do other dangerous activities until you know how pregabalin capsules affects you.
Ask your healthcare provider about when it will be okay to do these activities. What are pregabalin capsules? Pregabalin capsule is a prescription medicine used in adults, 18 years of age and older to treat: pain from damaged nerves (neuropathic pain) that happens with diabetes pain from damaged nerves (neuropathic pain) that follows healing of shingles fibromyalgia (pain all over your body) pain from damaged nerves (neuropathic pain) that follows spinal cord injury It is not known if pregabalin capsules is safe and effective in people under 18 years of age for the treatment of fibromyalgia and neuropathic pain with diabetes, shingles, or spinal cord injury.
Pregabalin capsule is a prescription medicine used in people 1 month of age and older to treat: partial-onset seizures when taken together with other seizure medicines. For the treatment of par… [Excerpted — this section continues on DailyMed.]
🍼 Nursing Mothers ▾
8.3Females and Males of Reproductive Potential Infertility Males Effects on Spermatogenesis In a randomized, double-blind, placebo-controlled non-inferiority study to assess the effect of pregabalin on sperm characteristics, healthy male subjects received pregabalin at a daily dose up to 600 mg (n=111) or placebo (n=109) for 13 weeks (one complete sperm cycle) followed by a 13-week washout period (off-drug). A total of 65 subjects in the pregabalin group (59%) and 62 subjects in the placebo group (57%) were included in the per protocol (PP) population.
These subjects took study drug for at least 8 weeks, had appropriate timing of semen collections and did not have any significant protocol violations. Among these subjects, approximately 9% of the pregabalin group (6/65) vs. 3% in the placebo group (2/62) had greater than or equal to 50% reduction in mean sperm concentrations from baseline at Week 26 (the primary endpoint).
The difference between pregabalin and placebo was within the pre-specified non-inferiority margin of 20%. There were no adverse effects of pregabalin on sperm morphology, sperm motility, serum FSH or serum testosterone levels as compared to placebo. In subjects in the PP population with greater than or equal to 50% reduction in sperm concentration from baseline, sperm concentrations were no longer reduced by greater than or equal to 50% in any affected subject after an additional 3 months off-drug.
In one subject, however, subsequent semen analyses demonstrated reductions from baseline of greater than or equal to 50% at 9 and 12 months off-drug. The clinical relevance of these data is unknown. In the animal fertility study with pregabalin in male rats, adverse reproductive and developmental effects were observed [see Nonclinical Toxicology ( 13.1 )].
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Pregabalin is well absorbed after oral administration, is eliminated largely by renal excretion, and has an elimination half-life of about 6 hours. Absorption and Distribution Following oral administration of pregabalin capsules under fasting conditions, peak plasma concentrations occur within 1.5 hours. Pregabalin oral bioavailability is greater than or equal to 90% and is independent of dose.
Following single-(25 to 300 mg) and multiple-dose (75 to 900 mg/day) administration, maximum plasma concentrations (C max ) and area under the plasma concentration-time curve (AUC) values increase linearly. Following repeated administration, steady state is achieved within 24 to 48 hours. Multiple-dose pharmacokinetics can be predicted from single-dose data.
The rate of pregabalin absorption is decreased when given with food, resulting in a decrease in C max of approximately 25% to 30% and an increase in T max to approximately 3 hours. However, administration of pregabalin with food has no clinically relevant effect on the total absorption of pregabalin. Therefore, pregabalin can be taken with or without food.
Pregabalin does not bind to plasma proteins. The apparent volume of distribution of pregabalin following oral administration is approximately
0.5L/kg. Pregabalin is a substrate for system L transporter which is responsible for the transport of large amino acids across the blood brain barrier. Although there are no data in humans, pregabalin has been shown to cross the blood brain barrier in mice, rats, and monkeys.
In addition, pregabalin has been shown to cross the placenta in rats and is present in the milk of lactating rats. Metabolism and Elimination Pregabalin undergoes negligible metabolism in humans. Following a dose of radiolabeled pregabalin, approximately 90% of the administered dose was recovered in the urine as unchanged pregabalin.
The N-methylated derivative of pregabalin, the major metabolite of pregabalin found in urine, accounted for 0.9% of the dose. In preclinical studies, pregabalin (S-enantiomer) did not undergo racemization to the R-enantiomer in mice, rats, rabbits, or monkeys. Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug with a mean elimination half-life of 6.3 hours in subjects with normal renal function.
Mean renal clearance was estimated to be 67.0 to 80.9 mL/min in young healthy subjects. Because pregabalin is not bound to plasma proteins this clearance rate indicates that renal tubular reabsorption is involved. Pregabalin elimination is nearly proportional to creatinine clearance (CLcr) [see Dosage and Administration ( 2.7 )].
Pharmacokinetics in Specific Populations Race In population pharmacokinetic analyses of the clinical studies in various populations, the pharmacokinetics of pregabalin were not significantly affected by race (Caucasians, Blacks, and Hispanics). Gender Population pharmacokinetic analyses of the clinical studies showed that the relationship between daily dose and pregabalin drug exposure is similar between genders. Renal Impairment and Hemodialysis Pregabalin clearance is nearly proportional to creatinine clearance (CLcr).
Dosage reduction in patients with renal dysfunction is necessary. Pregabalin is effectively removed from plasma by hemodialysis. Following a 4-hour hemodialysis treatment, plasma pregabalin concentrations are reduced by approximately 50%.
For patients on hemodialysis, dosing must be modified [ see Dosage and Administration ( 2.7 )]. Elderly Pregabalin oral clearance tended to decrease with increasing age. This decrease in pregabalin oral clearance is consistent with age-related decreases in CLcr.
Reduction of pregabalin dose may be required in patients who have age-related compromised renal function [ see Dosage and Administration ( 2.7 )]. Pediatric Pharmacokinetics Pediatric Patients (3 months to less than 17 years of age) Pregabalin pharmacokinetics were evaluated in 358 pediatric… [Excerpted — this section continues on DailyMed.]
🔬 Clinical Studies ▾
14 CLINICAL STUDIES
14.1Neuropathic Pain Associated with Diabetic Peripheral Neuropathy The efficacy of the maximum recommended dose of pregabalin for the management of neuropathic pain associated with diabetic peripheral neuropathy was established in three double-blind, placebo-controlled, multicenter studies with three times a day dosing, two of which studied the maximum recommended dose. Patients were enrolled with either Type 1 or Type 2 diabetes mellitus and a diagnosis of painful distal symmetrical sensorimotor polyneuropathy for 1 to 5 years.
A total of 89% of patients completed Studies DPN 1 and DPN 2. The patients had a minimum mean baseline pain score of greater than or equal to 4 on an 11-point numerical pain rating scale ranging from 0 (no pain) to 10 (worst possible pain). The baseline mean pain scores across the two studies ranged from 6.1 to 6.7.
Patients were permitted up to 4 grams of acetaminophen per day as needed for pain, in addition to pregabalin. Patients recorded their pain daily in a diary. Study DPN 1: This 5-week study compared pregabalin 25, 100, or 200 mg three times a day with placebo.
Treatment with pregabalin 100 mg and 200 mg three times a day statistically significantly improved the endpoint mean pain score and increased the proportion of patients with at least a 50% reduction in pain score from baseline. There was no evidence of a greater effect on pain scores of the 200 mg three times a day dose than the 100 mg three times a day dose, but there was evidence of dose dependent adverse reactions [see Adverse Reactions ( 6.1 )] . For a range of levels of improvement in pain intensity from baseline to study endpoint, Figure 1 shows the fraction of patients achieving that level of improvement.
The figure is cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study.
Figure 1: Patients Achieving Various Levels of Improvement in Pain Intensity – Study DPN 1 Study DPN 2: This 8-week study compared pregabalin 100 mg three times a day with placebo. Treatment with pregabalin 100 mg three times a day statistically significantly improved the endpoint mean pain score and increased the proportion of patients with at least a 50% reduction in pain score from baseline. For various levels of improvement in pain intensity from baseline to study endpoint, Figure 2 shows the fraction of patients achieving that level of improvement.
The figure is cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement. Some patients experienced a decrease in pain as early as Week 1, which persisted throughout the study.
Figure 2: Patients Achieving Various Levels of Improvement in Pain Intensity– Study DPN 2 Study DPN 1 Study DPN 2
14.2Postherpetic Neuralgia The efficacy of pregabalin for the management of postherpetic neuralgia was established in three double-blind, placebo-controlled, multicenter studies. These studies enrolled patients with neuralgia persisting for at least 3 months following healing of herpes zoster rash and a minimum baseline score of greater than or equal to 4 on an 11-point numerical pain rating scale ranging from 0 (no pain) to 10 (worst possible pain). Seventy-three percent of patients completed the studies.
The baseline mean pain scores across the 3 studies ranged from 6 to 7. Patients were permitted up to 4 grams of acetaminophen per day as needed for pain, in addition to pregabalin. Patients recorded their pain daily in a diary.
Study PHN 1: This 13-week study compared pregabalin 75, 150, and 300 mg twice daily with placebo. Patients with creatinine clearance (CLcr) between 30 to 60 mL/min were randomized to… [Excerpted — this section continues on DailyMed.]
🔒 Drug Abuse and Dependence ▾
9 DRUG ABUSE AND DEPENDENCE
9.1Controlled Substance Pregabalin is a Schedule V controlled substance. Pregabalin is not known to be active at receptor sites associated with drugs of abuse. As with any CNS active drug, carefully evaluate patients for history of drug abuse and observe them for signs of pregabalin misuse or abuse (e.g., development of tolerance, dose escalation, drug-seeking behavior).
9.2Abuse In a study of recreational users (N=15) of sedative/hypnotic drugs, including alcohol, pregabalin (450 mg, single dose) received subjective ratings of "good drug effect," "high" and "liking" to a degree that was similar to diazepam (30 mg, single dose). In controlled clinical studies in over 5,500 patients, 4 % of pregabalin -treated patients and 1 % of placebo-treated patients overall reported euphoria as an adverse reaction, though in some patient populations studied, this reporting rate was higher and ranged from 1 to 12%.
9.3Dependence In clinical studies, following abrupt or rapid discontinuation of pregabalin, some patients reported symptoms including insomnia, nausea, headache or diarrhea [see Warnings and Precautions ( 5.4 )] , consistent with physical dependence. In the postmarketing setting, in addition to these reported symptoms, other reported adverse reactions include, but are not limited to, seizures, depression, suicidal ideation and behavior, agitation, confusion, disorientation, psychotic symptoms, pain, sweating, tremor, dizziness, and malaise.
🔒 Controlled Substance ▾
9.1Controlled Substance Pregabalin is a Schedule V controlled substance. Pregabalin is not known to be active at receptor sites associated with drugs of abuse. As with any CNS active drug, carefully evaluate patients for history of drug abuse and observe them for signs of pregabalin misuse or abuse (e.g., development of tolerance, dose escalation, drug-seeking behavior).
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis A dose-dependent increase in the incidence of malignant vascular tumors (hemangiosarcomas) was observed in two strains of mice (B6C3F1 and CD-1) given pregabalin (200, 1,000, or 5,000 mg/kg) in the diet for two years. Plasma pregabalin exposure (AUC) in mice receiving the lowest dose that increased hemangiosarcomas was approximately equal to the human exposure at the maximum recommended dose (MRD) of 600 mg/day. A no-effect dose for induction of hemangiosarcomas in mice was not established.
No evidence of carcinogenicity was seen in two studies in Wistar rats following dietary administration of pregabalin for two years at doses (50, 150, or 450 mg/kg in males and 100, 300, or 900 mg/kg in females) that were associated with plasma exposures in males and females up to approximately 14 and 24 times, respectively, human exposure at the MRD. Mutagenesis Pregabalin was not mutagenic in bacteria or in mammalian cells in vitro , was not clastogenic in mammalian systems in vitro and in vivo , and did not induce unscheduled DNA synthesis in mouse or rat hepatocytes.
Impairment of Fertility In fertility studies in which male rats were orally administered pregabalin (50 to 2,500 mg/kg) prior to and during mating with untreated females, a number of adverse reproductive and developmental effects were observed. These included decreased sperm counts and sperm motility, increased sperm abnormalities, reduced fertility, increased preimplantation embryo loss, decreased litter size, decreased fetal body weights, and an increased incidence of fetal abnormalities. Effects on sperm and fertility parameters were reversible in studies of this duration (3 to 4 months).
The no-effect dose for male reproductive toxicity in these studies (100 mg/kg) was associated with a plasma pregabalin exposure (AUC) approximately 3 times human exposure at the maximum recommended dose (MRD) of 600 mg/day. In addition, adverse reactions on reproductive organ (testes, epididymides) histopathology were observed in male rats exposed to pregabalin (500 to 1,250 mg/kg) in general toxicology studies of four weeks or greater duration. The no-effect dose for male reproductive organ histopathology in rats (250 mg/kg) was associated with a plasma exposure approximately 8 times human exposure at the MRD.
In a fertility study in which female rats were given pregabalin (500, 1,250, or 2,500 mg/kg) orally prior to and during mating and early gestation, disrupted estrous cyclicity and an increased number of days to mating were seen at all doses, and embryolethality occurred at the highest dose. The low dose in this study produced a plasma exposure approximately 9 times that in humans receiving the MRD. A no-effect dose for female reproductive toxicity in rats was not established.
13.2Animal Toxicology and/or Pharmacology Dermatopathy Skin lesions ranging from erythema to necrosis were seen in repeated-dose toxicology studies in both rats and monkeys. The etiology of these skin lesions is unknown. At the maximum recommended human dose (MRD) of 600 mg/day, there is a 2-fold safety margin for the dermatological lesions.
The more severe dermatopathies involving necrosis were associated with pregabalin exposures (as expressed by plasma AUCs) of approximately 3 to 8 times those achieved in humans given the MRD. No increase in incidence of skin lesions was observed in clinical studies. Ocular Lesions Ocular lesions (characterized by retinal atrophy [including loss of photoreceptor cells] and/or corneal inflammation/mineralization) were observed in two lifetime carcinogenicity studies in Wistar rats.
These findings were observed at plasma pregabalin exposures (AUC) greater than or equal to 2 times those achieved in humans given the maximum recommended dose of 600 mg/day. A no-effect dose for ocular lesions was not established. Similar lesions were not observed in lifetime carcinogenicity studie… [Excerpted — this section continues on DailyMed.]
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis A dose-dependent increase in the incidence of malignant vascular tumors (hemangiosarcomas) was observed in two strains of mice (B6C3F1 and CD-1) given pregabalin (200, 1,000, or 5,000 mg/kg) in the diet for two years. Plasma pregabalin exposure (AUC) in mice receiving the lowest dose that increased hemangiosarcomas was approximately equal to the human exposure at the maximum recommended dose (MRD) of 600 mg/day. A no-effect dose for induction of hemangiosarcomas in mice was not established.
No evidence of carcinogenicity was seen in two studies in Wistar rats following dietary administration of pregabalin for two years at doses (50, 150, or 450 mg/kg in males and 100, 300, or 900 mg/kg in females) that were associated with plasma exposures in males and females up to approximately 14 and 24 times, respectively, human exposure at the MRD. Mutagenesis Pregabalin was not mutagenic in bacteria or in mammalian cells in vitro , was not clastogenic in mammalian systems in vitro and in vivo , and did not induce unscheduled DNA synthesis in mouse or rat hepatocytes.
Impairment of Fertility In fertility studies in which male rats were orally administered pregabalin (50 to 2,500 mg/kg) prior to and during mating with untreated females, a number of adverse reproductive and developmental effects were observed. These included decreased sperm counts and sperm motility, increased sperm abnormalities, reduced fertility, increased preimplantation embryo loss, decreased litter size, decreased fetal body weights, and an increased incidence of fetal abnormalities. Effects on sperm and fertility parameters were reversible in studies of this duration (3 to 4 months).
The no-effect dose for male reproductive toxicity in these studies (100 mg/kg) was associated with a plasma pregabalin exposure (AUC) approximately 3 times human exposure at the maximum recommended dose (MRD) of 600 mg/day. In addition, adverse reactions on reproductive organ (testes, epididymides) histopathology were observed in male rats exposed to pregabalin (500 to 1,250 mg/kg) in general toxicology studies of four weeks or greater duration. The no-effect dose for male reproductive organ histopathology in rats (250 mg/kg) was associated with a plasma exposure approximately 8 times human exposure at the MRD.
In a fertility study in which female rats were given pregabalin (500, 1,250, or 2,500 mg/kg) orally prior to and during mating and early gestation, disrupted estrous cyclicity and an increased number of days to mating were seen at all doses, and embryolethality occurred at the highest dose. The low dose in this study produced a plasma exposure approximately 9 times that in humans receiving the MRD. A no-effect dose for female reproductive toxicity in rats was not established.
📄 Recent Major Changes ▾
Warnings and Precautions ( 5.3 , 5.4 ) 04/2025
📄 Package Label / Principal Display Panel ▾
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 67877-462-90 Pregabalin Capsules 25 mg Rx Only 90 Capsules NDC 67877-463-05 Pregabalin Capsules 50 mg Rx Only 500 Capsules NDC 67877-464-90 Pregabalin Capsules 75 mg Rx only 90 Capsules NDC 67877-465-90 Pregabalin Capsules 100 mg Rx only 90 Capsules NDC 67877-466-90 Pregabalin Capsules 150 mg Rx only 90 Capsules NDC 67877-467-05 Pregabalin Capsules 200 mg Rx only 500 Capsules NDC 67877-468-90 Pregabalin Capsules 225 mg Rx only 90 Capsules NDC 67877-469-90 Pregabalin Capsules 300 mg Rx only 90 Capsules prega-25mg-90s-a prega-50mg-500s-a Pregabalin 75 mg 90 Counts prega-100mg-90s-a prega-150mg-90s-a prega-200mg-500s-a prega-225mg-90s-a prega-300mg-90s-a
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