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Pregabalin

Medically reviewed on September 10, 2018

Pronunciation

See also: Lyrica

(pre GAB a lin)

Index Terms

  • CI-1008
  • S-(+)-3-isobutylgaba

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Lyrica: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, 300 mg [contains corn starch]

Solution, Oral:

Lyrica: 20 mg/mL (473 mL) [contains methylparaben, propylparaben]

Tablet Extended Release 24 Hour, Oral:

Lyrica CR: 82.5 mg, 165 mg, 330 mg

Brand Names: U.S.

  • Lyrica
  • Lyrica CR

Pharmacologic Category

  • Anticonvulsant, Miscellaneous
  • GABA Analog

Pharmacology

Binds to alpha-2-delta subunit of voltage-gated calcium channels within the CNS and modulates calcium influx at the nerve terminals, thereby inhibiting excitatory neurotransmitter release including glutamate, norepinephrine (noradrenaline), serotonin, dopamine, substance P, and calcitonin gene-related peptide (Gajraj 2007; McKeage 2009). Although structurally related to GABA, it does not bind to GABA or benzodiazepine receptors. Exerts antinociceptive and anticonvulsant activity. Pregabalin may also affect descending noradrenergic and serotonergic pain transmission pathways from the brainstem to the spinal cord.

Absorption

Extended release: AUC is approximately 30% lower when administered while fasting

Distribution

Vd: 0.5 L/kg

Metabolism

Negligible

Excretion

Urine (90% as unchanged drug; minor metabolites)

Onset of Action

Pain management: Effects may be noted as early as the first week of therapy

Time to Peak

Extended release: Median: 8 hours with food (range: 5 to 12 hours)

Immediate release: Children ≥4 years and Adolescents <17 years: 0.5 to 2 hours fasting; Median: 0.7 hours fasting (range: 0.7 to 1.5 hours), 3 hours with food

Half-Life Elimination

Mean: Children 4 to 6 years: 3 to 4 hours; Children ≥7 years and Adolescents <17 years: 4 to 6 hours; Adults: 6.3 hours

Protein Binding

0%

Special Populations: Elderly

Oral clearance tends to decrease with increasing age.

Use: Labeled Indications

Fibromyalgia (immediate release only): For the management of fibromyalgia

Neuropathic pain associated with diabetic peripheral neuropathy (immediate release and extended release): For the management of neuropathic pain associated with diabetic peripheral neuropathy

Neuropathic pain associated with spinal cord injury (immediate release only): For the management of neuropathic pain associated with spinal cord injury

Partial-onset seizures, adjunctive therapy (immediate release only): Adjunctive therapy in patients ≥4 years with partial-onset seizures

Postherpetic neuralgia (immediate release and extended release): For the management of postherpetic neuralgia

Off Label Uses

Generalized anxiety disorder

Data from several meta-analyses support the use of pregabalin in the treatment of generalized anxiety disorder. Additional trials may be necessary to further define the role of pregabalin in this condition.

Based on the World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders, pregabalin is effective and recommended as a first-line agent in the management of generalized anxiety disorder.

Restless legs syndrome

Data from randomized, double-blind, placebo-controlled studies support the use of pregabalin in the treatment of moderate to severe primary restless legs syndrome (RLS) with predominant evening symptoms. Additional trials may be necessary to further define the role of pregabalin in this condition.

Based on American Academy of Neurology guidelines and guidelines from the International Restless Legs Syndrome Study Group for the long-term treatment of RLS, pregabalin is effective and recommended in the management of primary RLS.

Based on the International Restless Legs Syndrome Study Group (IRLSSG), European Restless Legs Syndrome Study Group (ERLSSG), and Restless Legs Syndrome Foundation guidelines for the prevention and treatment of dopaminergic augmentation in restless legs syndrome, alpha-2-delta ligands (eg, pregabalin), are effective and should be considered for the initial treatment of patients with RLS due to their minimal risk of augmentation. Additionally, patients who experience augmentation on dopaminergic agents may benefit from a switch to alpha-2-delta ligands (eg, pregabalin).

Social anxiety disorder

Data from two double-blind, placebo-controlled, fixed-dose studies and a relapse prevention study supports the use of pregabalin in the treatment of social anxiety disorder [Feltner 2011], [Griest 2011], [Pande 2004]. Additional trials may be necessary to further define the role of pregabalin in this condition.

Vasomotor symptoms associated with menopause

Data from a randomized, double-blind, placebo-controlled trial support the use of pregabalin in the treatment of vasomotor symptoms associated with menopause (hot flashes), including women previously treated for breast cancer [Loprinzi 2010]. Additional trials may be necessary to further define the role of pregabalin in this condition.

Based on the Endocrine Society (ES) Treatment of Symptoms of the Menopause guideline and the North American Menopause Society (NAMS) Nonhormonal Management of Menopause-associated Vasomotor Symptoms guideline, pregabalin is an effective and recommended alternative for the management of vasomotor symptoms associated with menopause in patients with contraindications to hormonal therapy or who prefer not to use hormonal therapy.

Contraindications

Hypersensitivity (eg, angioedema) to pregabalin or any component of the formulation

Dosing: Adult

Note: When discontinuing, taper off gradually over at least 1 week.

Fibromyalgia: Immediate release: Oral: Initial: 150 mg/day in divided doses (75 mg twice daily); may be increased to 300 mg/day (150 mg twice daily) within 1 week based on tolerability and effect; may be further increased to 450 mg/day (225 mg twice daily). Maximum dose: 450 mg/day (dosages up to 600 mg/day were evaluated with no significant additional benefit and an increase in adverse effects)

Neuropathic pain, diabetes-associated:

Immediate release: Oral: Initial: 150 mg/day in divided doses (50 mg 3 times daily); may be increased within 1 week based on tolerability and effect; maximum dose: 300 mg/day in 3 divided doses (dosages up to 600 mg/day were evaluated with no significant additional benefit and an increase in adverse effects)

Extended release: Oral: Initial: 165 mg once daily; dosage may be increased to 330 mg once daily within 1 week, based on response and tolerability. Maximum: 330 mg/day (dosages up to 600 mg/day of the immediate release formulation were evaluated with no significant additional benefit and an increase in adverse effects)

Neuropathic pain, spinal cord injury associated: Immediate release: Oral: Initial: 150 mg/day in divided doses (75 mg twice daily); may be increased to 300 mg/day (150 mg twice daily) within 1 week based on tolerability and effect; further titration to 600 mg/day (300 mg twice daily) after 2 to 3 weeks may be considered in patients who do not experience sufficient relief of pain provided they are able to tolerate pregabalin. Maximum dose: 600 mg/day

Partial-onset seizures (adjunctive therapy): Immediate release: Oral: Initial: 150 mg/day in 2 or 3 divided doses; may be increased based on tolerability and effect (optimal titration schedule has not been defined). Maximum dose: 600 mg/day

Postherpetic neuralgia:

Immediate release: Oral: Initial: 150 mg/day in divided doses (75 mg twice daily or 50 mg 3 times daily); may be increased to 300 mg/day within 1 week based on tolerability and effect; further titration (to 600 mg/day) after 2 to 4 weeks may be considered in patients who do not experience sufficient relief of pain provided they are able to tolerate pregabalin. Maximum dose: 600 mg/day

Extended release: Oral: Initial: 165 mg once daily; dosage may be increased to 330 mg once daily within 1 week, based on response and tolerability. After 2 to 4 weeks of treatment, dosage may be increased to 660 mg once daily in patients tolerating therapy but not experiencing adequate pain relief. Maximum: 660 mg/day.

Conversion from immediate-release oral formulations to extended-release oral formulation: Note: On the day of the switch, administer morning dose of immediate-release product as prescribed, and initiate extended-release therapy after the evening meal.

Immediate-release total daily dose of 75 mg is equivalent to extended-release dose of 82.5 mg once daily

Immediate-release total daily dose of 150 mg is equivalent to extended-release dose of 165 mg once daily

Immediate-release total daily dose of 225 mg is equivalent to extended-release dose of 247.5 mg once daily

Immediate-release total daily dose of 300 mg is equivalent to extended-release dose of 330 mg once daily

Immediate-release total daily dose of 450 mg is equivalent to extended-release dose of 495 mg once daily

Immediate-release total daily dose of 600 mg is equivalent to extended-release dose of 660 mg once daily

Generalized anxiety disorder (off-label use): Immediate release: Oral: Initial: 150 mg/day in 2 to 3 divided doses; based on response and tolerability, adjust dose at weekly intervals in increments of 150 mg to a maximum dose of 600 mg/day (Frampton 2014; WFSBP [Bandelow 2008]).

Restless legs syndrome (off-label use): Immediate release: Oral: Initial: 75 mg daily, 1 to 3 hours before bedtime; then increase to 150 mg daily on day 6. On or after day 11, dosage may be further increased to 300 mg daily. Usual effective dose: 150 to 450 mg/day (Allen 2010; Allen 2014; Garcia-Borreguero 2014).

Social anxiety disorder (off-label use): Immediate release: Oral: Initial: 300 mg/day in 3 divided doses; on day 4, based on response and tolerability, increase dose to 450 mg/day. On or after day 6, dosage may be further increased to 600 mg/day. In clinical trials, efficacy for response and relapse prevention was found at doses of 450 and 600 mg/day (Feltner 2011; Greist 2011; Pande 2004).

Vasomotor symptoms associated with menopause (off-label use): Immediate release: Oral: Initial: 50 mg daily at bedtime; increase to 50 mg twice daily after 1 week and then increase to 75 mg twice daily after 1 week. Dose can be increased to 150 mg twice daily after 1 week, based on response and tolerability (Loprinzi 2010).

Dosing: Geriatric

Refer to adult dosing; use with caution. In the management of restless legs syndrome, a starting dose of 50 mg once daily in patients >65 years has been recommended (Garcia-Borreguero 2016).

Dosing: Pediatric

Note: When discontinuing, taper off gradually over at least 1 week.

Seizures, partial onset; adjunctive therapy: Immediate release:

Children ≥4 years and Adolescents <17 years:

11 to <30 kg: Oral: Initial dose: 3.5 mg/kg/day in 2 or 3 divided doses; dose may be increased weekly based on clinical response and tolerability (optimal titration schedule has not been defined). Maximum daily dose: 14 mg/kg/day

≥30 kg: Oral: Initial dose: 2.5 mg/kg/day in 2 or 3 divided doses; dose may be increased weekly based on clinical response and tolerability (optimal titration schedule has not been defined). Maximum daily dose: 10 mg/kg/day, not to exceed 600 mg/day

Adolescents ≥17 years: Oral: Initial dose: 150 mg daily in 2 or 3 divided doses; may be increased weekly based on tolerability and effect (optimal titration schedule has not been defined). Maximum daily dose: 600 mg/day

Dosing: Renal Impairment

Immediate release: Renal function may be estimated using the Cockcroft-Gault formula. Then determine recommended dosage regimen based on the indication-specific total daily dose for normal renal function (CrCl ≥60 mL/minute). For example, if the indication-specific daily dose is 450 mg daily for normal renal function, the daily dose should be reduced to 225 mg daily (in 2 to 3 divided doses) for a creatinine clearance of 30 to 60 mL/minute (see table).

Immediate-Release Pregabalin Renal Impairment Dosing

CrCl

(mL/minute)

Total Pregabalin Daily Dose

(mg/day)

Dosing Frequency

Posthemodialysis supplementary dosage (as a single additional dose):

25 mg/day schedule: Single supplementary dose of 25 mg or 50 mg

25 to 50 mg/day schedule: Single supplementary dose of 50 mg or 75 mg

50 to 75 mg/day schedule: Single supplementary dose of 75 mg or 100 mg

75 mg/day schedule: Single supplementary dose of 100 mg or 150 mg

≥60 (normal renal function)

150

300

450

600

2 to 3 divided doses

30 to 60

75

150

225

300

2 to 3 divided doses

15 to 30

25 to 50

75

100-150

150

1 to 2 divided doses

<15

25

25 to 50

50 to 75

75

Single daily dose

Table has been converted to the following text.

Immediate-Release Pregabalin Renal Impairment Dosing

CrCl ≥60 mL/minute (normal renal function): No dosage adjustment required.

150 mg in 2 to 3 divided doses or

300 mg in 2 to 3 divided doses or

450 mg in 2 to 3 divided doses or

600 mg in 2 to 3 divided doses

CrCl 30 to 60 mL/minute: Total daily dose:

75 mg in 2 to 3 divided doses or

150 mg in 2 to 3 divided doses or

225 mg in 2 to 3 divided doses or

300 mg in 2 to 3 divided doses

CrCl 15 to 30 mL/minute: Total daily dose:

25 to 50 mg in once daily or in 2 divided doses or

75 mg once daily or in 2 divided doses or

100 to 150 mg once daily or in 2 divided doses or

150 mg once daily or in 2 divided doses

CrCl <15 mL/minute: Total daily dose:

25 mg once daily or

25 to 50 mg once daily or

50 to 75 mg once daily or

75 mg once daily

Hemodialysis: Total daily dose (as a single posthemodialysis supplementary dose):

25 mg: Single supplementary dose of 25 mg or 50 mg

25 to 50 mg: Single supplementary dose of 50 mg or 75 mg

50 to 75 mg: Single supplementary dose of 75 mg or 100 mg

75 mg: Single supplementary dose of 100 mg or 150 mg

Extended release: Renal function may be estimated using the Cockcroft-Gault formula. Then determine recommended dosage regimen based on the indication-specific total daily dose for normal renal function (CrCl ≥60 mL/minute). For example, if the indication-specific daily dose is 495 mg once daily for normal renal function, the daily dose should be reduced to 247.5 mg once daily for a creatinine clearance of 30 to 60 mL/minute (see table).

Extended-Release Pregabalin Renal Impairment Dosing

CrCl (mL/minute)

Total Pregabalin Daily Dose (mg/day)

Dosing Frequency

≥60 (normal renal function)

165

330

495

660

Once daily

30 to 60

82.5

165

247.5

330

Once daily

<30

Extended-release product not recommended; use immediate-release product

Hemodialysis

Table has been converted to the following text.

Extended-Release Pregabalin Renal Impairment Dosing

CrCl ≥60 mL/minute (normal renal function): No dosage adjustment required.

165 mg once daily or

330 mg once daily or

495 mg once daily or

660 mg once daily

CrCl 30 to 60 mL/minute: Total daily dose:

82.5 mg once daily or

165 mg once daily or

247.5 mg once daily or

330 mg once daily

CrCl <30 mL/minute: Use is not recommended; use immediate-release product

Hemodialysis: Use is not recommended; use immediate-release product

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling. However, no adjustment is expected since undergoes minimal hepatic metabolism.

Administration

Immediate release: May be administered with or without food.

Extended release: Administer once daily after an evening meal; swallow whole, do not split, crush, or chew. A missed dose should be taken before bedtime following a snack. If missed before bedtime, administer in the morning with a meal. If missed in the morning, wait until the evening meal to take the next scheduled dose.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: May enhance the adverse/toxic effect of Pregabalin. Specifically, the risk of angioedema may be increased. Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Consider therapy modification

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Mianserin: May diminish the therapeutic effect of Anticonvulsants. Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Opioid Analgesics: CNS Depressants may enhance the CNS depressant effect of Opioid Analgesics. Management: Avoid concomitant use of opioid analgesics and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Orlistat: May decrease the serum concentration of Anticonvulsants. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Thiazolidinediones: Pregabalin may enhance the fluid-retaining effect of Thiazolidinediones. Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Adverse Reactions

>10%:

Cardiovascular: Peripheral edema (4% to 16%)

Central nervous system: Dizziness (3% to 45%), drowsiness (≤36%; children and adolescents: 17% to 26%), headache (2% to 14%), fatigue (4% to 11%)

Endocrine & metabolic: Weight gain (2% to 14%)

Gastrointestinal: Xerostomia (≤15%)

Ophthalmic: Visual field loss (13%), blurred vision (≤12%)

1% to 10%:

Cardiovascular: Edema (≤8%), facial edema (1% to 3%), chest pain (2%), hypertension (2%), hypotension (2%)

Central nervous system: Ataxia (2% to 9%), equilibrium disturbance (2% to 9%), abnormal gait (1% to 8%), euphoria (2% to 7%), confusion (1% to 7%), disturbance in attention (4% to 6%), abnormality in thinking (1% to 6%), neuropathy (5%), pain (3% to 5%), myasthenia (1% to 5%), insomnia (4%), amnesia (1% to 4%), memory impairment (1% to 4%), vertigo (1% to 4%), hypoesthesia (2% to 3%), feeling abnormal (1% to 3%), speech disturbance (1% to 3%), anxiety (2%), paresthesia (2%), disorientation (1% to 2%), intoxicated feeling (1% to 2%), lethargy (1% to 2%), anorgasmia (≥1%), depersonalization (≥1%), hypertonia (≥1%), sedation (≥1%), stupor (≥1%), twitching (≥1%; includes myokymia), nervousness (1%)

Dermatologic: Pressure ulcer (3%), ecchymoses (≥1%), pruritus (≥1%), contact dermatitis (1%)

Endocrine & metabolic: Fluid retention (2% to 3%), hypoglycemia (2% to 3%), decreased libido (≥1%)

Gastrointestinal: Constipation (3% to 10%), increased appetite (3% to 10%), nausea (3% to 5%), sialorrhea (children and adolescents: 1% to 4%), flatulence (2% to 3%), vomiting (1% to 3%), abdominal distension (2%), abdominal pain (≥1%), gastroenteritis (≥1%), diarrhea (1%), viral gastroenteritis (≤1%)

Genitourinary: Urinary incontinence (1% to 3%), impotence (≥1%), urinary frequency (≥1%), erectile dysfunction (≤1%), urinary tract infection (1%)

Hematologic & oncologic: Thrombocytopenia (3%)

Hepatic: Increased serum alanine aminotransferase (≤1%), increased serum aspartate aminotransferase (≤1%)

Hypersensitivity: Hypersensitivity reaction (≥1%)

Infection: Infection (6% to 8%)

Neuromuscular & skeletal: Asthenia (4% to 7%), arthralgia (1% to 6%), muscle spasm (4%), back pain (1% to 4%), limb pain (3%), neck pain (3%), increased creatine phosphokinase (2% to 3%), tremor (1% to 3%), joint swelling (≤2%), lower limb cramp (≥1%), myalgia (≥1%)

Ophthalmic: Decreased visual acuity (7%), visual disturbance (1% to 5%), diplopia (≤4%), eye disease (1% to 2%), conjunctivitis (≥1%), nystagmus (≥1%)

Otic: Otitis media (≥1%), tinnitus (≥1%)

Respiratory: Nasopharyngitis (1% to 8%), sinusitis (≤7%), bronchitis (3%), pharyngolaryngeal pain (3%), dyspnea (2%), flu-like symptoms (2%), cough (1%), respiratory tract infection (1%)

Miscellaneous: Accidental injury (3% to 6%), fever (≥1%)

Frequency not defined: Cardiovascular: Prolongation P-R interval on ECG

<1%, postmarketing, and/or case reports: Abnormal dreams, abscess, accommodation disturbance, acute renal failure, ageusia, agitation, albuminuria, alopecia, altered sense of smell, amenorrhea, anaphylactoid shock, anemia, angioedema, anisocoria, apathy, aphasia, aphthous stomatitis, apnea, arthropathy, ascites, atelectasis, balanitis, bladder neoplasm, blepharitis, blepharoptosis, blindness, bradykinesia, breast hypertrophy, bronchiolitis, cardiac failure, cellulitis, cerebellar syndrome, cervicitis, chills, cholecystitis, cholelithiasis, chondrodystrophy, cognitive dysfunction, cogwheel rigidity, colitis, coma, corneal ulcer, cutaneous nodule, decreased glucose tolerance, delirium, delusions, depression of ST segment on ECG, dermal ulcer, drug dependence, dry mucous membranes, dysarthria, dysautonomia, dysgeusia, dyskinesia, dysmenorrhea, dyspareunia, dysphagia, dystonia, dysuria, eczema, ejaculatory disorder, encephalopathy, eosinophilia, epididymitis, erythema, esophageal ulcer, esophagitis, exfoliative dermatitis, exophthalmos, extraocular palsy, extrapyramidal reaction, facial pain, gastritis, gastrointestinal hemorrhage, glomerulonephritis, glycosuria, granuloma, Guillain-Barre syndrome, gynecomastia, hallucination, hangover effect, heavy menstrual bleeding, hematuria, hemophthalmos, hiccups, hirsutism, hostility, hypalgesia, hyperacusis, hyperalgesia, hyperesthesia, hyperkinesia, hypochromic anemia, hypokinesia, hypoprothrombinemia, hypotonia, impaired consciousness, increased libido, increased neutrophils, increased serum lipase, intentional injury, intracranial hypertension, iritis, irritability, joint stiffness, keratitis, keratoconjunctivitis, lactation (females), laryngismus, leukocytosis, leukopenia, leukorrhea, lichenoid dermatitis, local inflammation (coccydynia), lymphadenopathy, malaise, manic reaction, melanosis, melena, miosis, mydriasis, myelofibrosis, myoclonus, nail disease, neck stiffness, nephritis, nephrolithiasis, neuralgia, nocturnal amblyopia, nonthrombocytopenic purpura, oliguria, ophthalmoplegia, optic atrophy, oral mucosa ulcer, oral paresthesia, orthostatic hypotension, ovarian disease, palpitations, pancreatitis, papilledema, paranoia, pelvic pain, periodontal abscess, periorbital edema, peripheral neuritis, personality disorder, petechial rash, photophobia, pneumonia, polycythemia, proteinuria, psychomotor disturbance, psychotic depression, pulmonary edema, pulmonary fibrosis, purpuric rash, pustular rash, pyelonephritis, rectal hemorrhage, retinal edema, retinal vascular disease, retroperitoneal fibrosis, rhabdomyolysis, sciatica, schizophrenia, severe thrombocytopenia, shock, skin atrophy, skin blister, skin necrosis, skin photosensitivity, skin rash, sleep disorder, Stevens-Johnson syndrome, subcutaneous nodule, syncope, tachycardia, thrombocythemia, thrombophlebitis, tongue edema, torticollis, trismus, urate crystalluria, urinary retention, urine abnormality, urticaria, uterine hemorrhage, uveitis, ventricular fibrillation, vesiculobullous dermatitis, wheezing, xeroderma, xerophthalmia, yawning

Warnings/Precautions

Concerns related to adverse effects:

• Angioedema: Angioedema has been reported during initial and chronic treatment; may be life-threatening. Symptoms reported include facial, mouth (tongue, lips, and gums), and neck (throat and larynx) swelling. Use with caution in patients with a history of angioedema episodes. Concurrent use with other drugs known to cause angioedema (eg, ACE inhibitors) may increase risk. Discontinue treatment immediately if angioedema occurs.

• CNS effects: Dizziness and somnolence are commonly reported; effects generally occur shortly after initiation and occur more frequently at higher doses. Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Hematologic effects: May decrease platelet count. Severe thrombocytopenia is extremely rare.

• Hypersensitivity: Hypersensitivity reactions, including skin redness, blistering, hives, rash, dyspnea, and wheezing have been reported shortly after initiation of treatment; discontinue treatment if hypersensitivity occurs.

• Peripheral edema: Use may cause peripheral edema; use with caution in patients with heart failure (NYHA Class III or IV) due to limited data in this patient population. In addition, effect on weight gain/edema may be additive with the thiazolidinedione class of antidiabetic agents; use caution when coadministering these agents, particularly in patients with prior cardiovascular disease.

• PR interval: May cause mild prolongation of PR interval. Clinical significance unknown.

• Rhabdomyolysis: Has been associated with increases in creatine kinase and rare cases of rhabdomyolysis; patients should be instructed to notify their prescriber if unexplained muscle pain, tenderness, or weakness, particularly if fever and/or malaise are associated with these symptoms. Discontinue treatment if myopathy is suspected or diagnosed or if markedly elevated creatine kinase levels occur.

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

• Visual disturbances: Blurred vision, decreased acuity and visual field changes have been associated with therapy; patients should be instructed to notify their physician if these effects are noted.

• Weight gain: Use may cause weight gain; weight gain generally associated with dose and duration (average weight gain was 5.2 kg for diabetic patients receiving pregabalin for ≥2 years); weight gain was not limited to patients with edema and did not appear to be associated with baseline BMI, gender, age, or loss of glycemic control in diabetic patients.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with severe cardiovascular disease, including heart failure; weight gain and/or peripheral edema may occur. In a scientific statement from the American Heart Association, pregabalin has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: minor to moderate) (AHA [Page 2016]).

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

• Substance abuse: Use with caution in patients with a history of substance abuse; potential for behavioral dependence in this population exists (Bonnet 2017).

Concurrent drug therapy issues:

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

Other warnings/precautions:

• Tumorigenic potential: Increased incidence of hemangiosarcoma noted in animal studies; significance of these findings in humans is unknown.

• Withdrawal: Anticonvulsants should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually unless safety concerns require a more rapid withdrawal. Tapering over at least 1 week is recommended. Abrupt discontinuation with pregabalin has been associated with anxiety, diarrhea, headache, hyperhidrosis, insomnia, and nausea.

Monitoring Parameters

Measures of efficacy (pain intensity/seizure frequency); degree of sedation; symptoms of myopathy; creatine kinase (as clinically indicated); symptoms of ocular disturbance; weight gain/edema; skin integrity (in patients with diabetes); signs and symptoms of suicidality (eg, suicidal thoughts, anxiety, depression, behavioral changes); platelet count (as clinically indicated)

Pregnancy Considerations

Pregabalin crosses the placenta (Ohman 2011). Studies which evaluated neonatal outcomes following pregabalin exposure during pregnancy are limited (Mostacci 2017; Patorno 2017; Veiby 2014; Winterfeld 2016). Pregabalin has been evaluated as an adjuvant pain medication following cesarean section and pregnancy termination (El Kenany 2016; Lavand'homme 2010).

In a study conducted in males, pregabalin was found to temporarily decrease mean sperm concentrations; no effects on sperm morphology or motility were observed. Concentrations increased after pregabalin was discontinued. The clinical relevance of this is not known.

Data collection to monitor pregnancy and infant outcomes following exposure to pregabalin is ongoing. Patients exposed to pregabalin during pregnancy are encouraged to enroll themselves into the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dizziness, weight gain, fatigue, difficulty focusing, headache, dry mouth, loss of strength and energy, constipation, nausea, or increased hunger. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or illogical thinking), vision changes, blurred vision, muscle pain, muscle weakness, seizures, bruising, bleeding, change in balance, confusion, tremors, memory impairment, shortness of breath, excessive weight gain, swelling of arms or legs, tachycardia, abnormal heartbeat, , chills, pharyngitis, skin sores, difficulty speaking, insomnia, abnormal gait, feeling high, agitation, irritability, panic attacks, or mood changes (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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