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  • CLASSES

    Anticonvulsants, Gabapentinoids
    Neuropathic Pain and Peripheral Neuropathy Agents

    DEA CLASS

    Rx, schedule V

    DESCRIPTION

    Oral compound chemically and structurally similar to gabapentin, with antiepileptic, analgesic, and anxiolytic properties
    Used for neuropathic pain associated with diabetic peripheral neuropathy or spinal cord injury, postherpetic neuralgia, fibromyalgia, and adjunctive therapy for partial onset seizures
    Monitor for emerging or worsening depression, suicidal thoughts/behavior, or mood/behavior changes

    COMMON BRAND NAMES

    Lyrica, Lyrica CR

    HOW SUPPLIED

    Lyrica CR Oral Tab ER: 82.5mg, 165mg, 330mg
    Lyrica/Pregabalin Oral Cap: 25mg, 50mg, 75mg, 100mg, 150mg, 200mg, 225mg, 300mg
    Lyrica/Pregabalin Oral Sol: 1mL, 20mg

    DOSAGE & INDICATIONS

    For the treatment of neuropathic pain, including neuropathic pain associated with diabetic neuropathy, postherpetic neuralgia, and spinal cord injury.
    For the treatment of neuropathic pain associated with peripheral diabetic neuropathy (DPN).
    Oral dosage (immediate-release)
    Adults

    50 mg PO 3 times daily, initially. May increase dose to 100 mg PO 3 times daily after 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; therefore, doses above 300 mg/day are not recommended. To discontinue, gradually taper the dose over a minimum of 1 week.

    Oral dosage (extended-release) in treatment-naive patients
    Adults

    165 mg PO once daily, initially. May increase dose to 330 mg PO once daily after 1 week based on efficacy and tolerability. After 2 to 4 weeks, may further increase dose to 660 mg PO once daily for patients who have ongoing pain and are tolerating 330 mg/day. Max dose: 660 mg once daily. To discontinue, gradually taper the dose over a minimum of 1 week.

    Oral dosage (extended-release) in patients switching from immediate-release products
    Adults

    82.5 mg/day of extended-release for 75 mg/day of immediate-release, 165 mg/day of extended-release for 150 mg/day of immediate-release, 247.5 mg of extended-release for 225 mg/day of immediate-release, 330 mg/day of extended-release for 300 mg/day immediate-release, 495 mg/day of extended-release for 450 mg/day immediate-release dose, or 660 mg/day of extended-release for 600 mg/day of immediate-release. To discontinue, gradually taper the dose over a minimum of 1 week.

    For the treatment of postherpetic neuralgia (PHN).
    Oral dosage (immediate-release)
    Adults

    75 mg PO twice daily or 50 mg PO 3 times daily, initially. May increase dose to 150 mg PO twice daily or 100 mg PO 3 times daily after 1 week based on efficacy and tolerability. After 2 to 4 weeks, may further increase dose to 300 mg PO twice daily or 200 mg PO 3 times daily for patients who have ongoing pain and are tolerating 300 mg/day. To discontinue, gradually taper the dose over a minimum of 1 week.

    Oral dosage (extended-release) in treatment-naive patients
    Adults

    165 mg PO once daily, initially. May increase dose to 330 mg PO once daily after 1 week based on efficacy and tolerability. After 2 to 4 weeks, may further increase dose to 660 mg PO once daily for patients who have ongoing pain and are tolerating 330 mg/day. Max dose: 660 mg once daily. To discontinue, gradually taper the dose over a minimum of 1 week.

    Oral dosage (extended-release) in patients switching from immediate-release products
    Adults

    82.5 mg/day of extended-release for 75 mg/day of immediate-release, 165 mg/day of extended-release for 150 mg/day of immediate-release, 247.5 mg of extended-release for 225 mg/day of immediate-release, 330 mg/day of extended-release for 300 mg/day immediate-release, 495 mg/day of extended-release for 450 mg/day immediate-release dose, or 660 mg/day of extended-release for 600 mg/day of immediate-release. To discontinue, gradually taper the dose over a minimum of 1 week.

    For the treatment of neuropathic pain associated with spinal cord injury.
    Oral dosage (immediate-release)
    Adults

    75 mg PO twice daily, initially. May increase dose to 150 mg PO twice daily after 1 week based on efficacy and tolerability. After 2 to 3 weeks, may further increase dose to 300 mg PO twice daily for patients who have ongoing pain and are tolerating 300 mg/day. To discontinue, gradually taper the dose over a minimum of 1 week.

    For the adjunctive treatment of partial seizures (with or without secondary generalization).
    Oral dosage (immediate-release)
    Adults

    150 mg/day PO divided in 2 or 3 doses, initially. May increase dose weekly based on efficacy and tolerability. Max: 600 mg/day.

    Adolescents 17 years

    150 mg/day PO divided in 2 or 3 doses, initially. May increase dose weekly based on efficacy and tolerability. Max: 600 mg/day.

    Children and Adolescents 16 years and younger weighing 30 kg or more

    2.5 mg/kg/day PO divided in 2 or 3 doses, initially. May increase dose weekly based on efficacy and tolerability. Max: 10 mg/kg/day or 600 mg/day.

    Children and Adolescents 4 to 16 years weighing less than 30 kg

    3.5 mg/kg/day PO divided in 2 or 3 doses, initially. May increase dose weekly based on efficacy and tolerability. Max: 14 mg/kg/day.

    Infants and Children 1 month to 3 years weighing less than 30 kg

    3.5 mg/kg/day PO divided in 3 doses, initially. May increase dose weekly based on efficacy and tolerability. Max: 14 mg/kg/day.

    For the treatment of fibromyalgia.
    Oral dosage (immediate-release)
    Adults

    75 mg PO twice daily, initially. May increase dose to 150 mg PO twice daily after 1 week based on efficacy and tolerability. May further increase the dose to 225 mg PO twice daily for patients who do not experience sufficient benefit on 300 mg/day. 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; therefore, doses above 450 mg/day are not recommended. To discontinue, gradually taper the dose over a minimum of 1 week. 

    For the treatment of social phobia (social anxiety disorder)†.
    Oral dosage (immediate-release)
    Adults

    200 mg PO 3 times daily. Doses are usually titrated to the target dose over 1 week.

    For the treatment of generalized anxiety disorder (GAD)†.
    Oral dosage (immediate-release)
    Adults

    75 mg PO twice daily, initially. May increase dose to 150 mg PO twice daily after 1 week based on efficacy and tolerability. Thereafter, adjust dose based on response and tolerability. Usual dose: 150 to 300 mg PO twice daily. Max: 300 mg PO twice daily. To discontinue, gradually taper the dose. Pregabalin is listed in Category A, along with several antidepressants, as having the highest level of evidence for efficacy in generalized anxiety disorder (GAD) based on significant efficacy in GAD from several clinical studies, a rapid onset of action similar to benzodiazepines, and mild to moderate side effect profile.

    Geriatric Adults

    50 mg PO once daily for 2 days, then 50 mg PO twice daily for 2 days, then 75 mg PO twice daily. Thereafter, adjust dose based on response and tolerability. Dose range: 150 to 600 mg/day PO divided in 2 or 3 doses. To discontinue, gradually taper the dose. Pregabalin is listed in Category A, along with several antidepressants, as having the highest level of evidence for efficacy in generalized anxiety disorder (GAD) based on significant efficacy in GAD from several clinical studies, a rapid onset of action similar to benzodiazepines, and mild to moderate side effect profile.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Immediate-release formulations: 300 mg/day PO for diabetic peripheral neuropathy; 600 mg/day PO for postherpetic neuralgia, neuropathic pain due to spinal cord injury, and adjunctive treatment of seizures; 450 mg/day PO for fibromyalgia.
    Extended-release tablets: 330 mg/day PO for diabetic peripheral neuropathy; 660 mg/day PO for postherpetic neuralgia.

    Geriatric

    Immediate-release formulations: 300 mg/day PO for diabetic peripheral neuropathy; 600 mg/day PO for postherpetic neuralgia, neuropathic pain due to spinal cord injury, and adjunctive treatment of seizures; 450 mg/day PO for fibromyalgia.
    Extended-release tablets: 330 mg/day PO for diabetic peripheral neuropathy; 660 mg/day PO for postherpetic neuralgia.

    Adolescents

    Immediate-release formulations:
    17 years: 600 mg/day PO for adjunctive treatment of partial seizures.
    13 to 16 years weighing 30 kg or more: 10 mg/kg/day PO (Max: 600 mg/day) for adjunctive treatment of partial seizures.
    13 to 16 years weighing less than 30 kg: 14 mg/kg/day PO for adjunctive treatment of partial seizures.
    Extended-release tablets: Safety and efficacy have not been established.

    Children

    Immediate-release formulations:
    Weighing 30 kg or more: 10 mg/kg/day PO (Max: 600 mg/day) for adjunctive treatment of partial seizures.
    Weighing less than 30 kg: 14 mg/kg/day PO for adjunctive treatment of partial seizures.
    Extended-release tablets: Safety and efficacy have not been established.

    Infants

    Immediate-release formulations: 14 mg/kg/day PO for adjunctive treatment of partial seizures.
    Extended-release tablets: Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    The following recommendations have been made for adults :
    CrCl 60 mL/minute or more: No dose adjustment needed.
    CrCl 30 to 60 mL/minute: 75 to 300 mg/day PO given in 2 or 3 divided doses for immediate-release formulations; reduce dose by 50% for extended-release tablets.
    CrCl 15 to 30 mL/minute: Immediate-release formulations: 25 to 150 mg/day PO given in 1 or 2 divided doses. Use of the extended-release tablet is not recommended.
    CrCl 15 mL/minute or less: 25 to 75 mg PO once daily. Use of the extended-release tablet is not recommended.
     
    Intermittent hemodialysis
    Use of extended-release tablets is not recommended; use immediate-release formulations. Pregabalin is effectively removed by hemodialysis. Each 4 hour hemodialysis session removes 50% to 60% of the amount of drug initially present in the circulation in patients on three times weekly hemodialysis, who were administered pregabalin roughly 24 hours prior to next scheduled dialysis session. For patients undergoing hemodialysis, pregabalin daily dose should be adjusted based on renal function. In addition to the daily dose adjustment, a supplemental dose should be given immediately following every 4-hour hemodialysis treatment. For patients receiving the 25 mg once a day regimen: take one supplemental dose of 25 or 50 mg. For patients receiving the 25 to 50 mg once a day regimen: take one supplemental dose of 50 or 75 mg. For patients receiving the 75 mg once a day regimen: take one supplemental dose of 100 or 150 mg.

    ADMINISTRATION

    Oral Administration

    When discontinuing pregabalin, taper the dose gradually over a minimum of 1 week.
     
    Immediate-release capsules and oral solution
    Both capsules and oral solution may be administered without regard to meals.
    Missed doses: Advise patients that if they miss a dose, then 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 2 doses at the same time.
     
    Extended-release tablets
    Administer after evening meal.
    Do not split, crush, or chew the tablet.
    When switching from immediate-release to extended-release pregabalin, on the day of the switch, instruct patients to take their morning dose of immediate-release pregabalin as prescribed and initiate extended-release pregabalin therapy after the evening meal.
    Missed doses: Advise patients that if they miss taking their dose of extended-release pregabalin after an evening meal, then they should take their usual dose before bedtime after a snack. If they miss taking the dose before bedtime, then they should take their usual dose after a morning meal. If they miss taking the dose after the morning meal, then they should take their usual dose at the usual time that evening after an evening meal.

    STORAGE

    Lyrica:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Lyrica CR:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in original container

    CONTRAINDICATIONS / PRECAUTIONS

    Angioedema

    Pregabalin is contraindicated in patients with known pregabalin hypersensitivity or with product specific ingredient hypersensitivity. It is not known if cross-hypersensitivity exists between gabapentin and pregabalin; however, the drugs are chemically and structurally similar. Use with caution in patients with a known hypersensitivity to gabapentin. There are post-marketing reports of hypersensitivity reactions (i.e., erythema, blisters, hives, rash, dyspnea, and wheezing) and life-threatening angioedema. Treatment with pregabalin should be discontinued immediately if these reactions occur. Caution is advised during use of pregabalin in patients with a history of angioedema. Concurrent use of other medications known to cause angioedema may increase the risk of this complication with use of pregabalin.

    Depression, suicidal ideation

    Antiepileptic drugs (AEDs), including pregabalin, increase the risk of suicidal ideation, thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to 1 of the AEDs had approximately twice the risk (adjusted RR 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients taking 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 1 case of suicidal thinking or behavior for every 530 patients treated. There were 4 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 was observed as early as 1 week after starting drug treatment and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5 to 100 years of age) in the clinical trials analyzed. The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. Closely monitor patients for emerging or worsening depression or suicidal thoughts/behavior. Patients and caregivers should be informed of the increased risk of suicidal thoughts and behaviors and should be advised to immediately report the emergence or worsening of depression, the emergence of suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior. Pregabalin should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose.

    CNS depression, driving or operating machinery, ethanol intoxication

    Pregabalin commonly causes CNS depression, including dizziness and drowsiness. Patients should be advised to use caution when driving or operating machinery, or performing other tasks that require mental alertness, until they are aware of whether pregabalin adversely affects their mental and/or motor performance. Patients should avoid the concomitant use of ethanol and should also avoid ethanol intoxication while receiving pregabalin due to the potential for additive drowsiness.

    Substance abuse

    Pregabalin may cause physical and psychological dependence, and should be used with extreme caution in patients with known, suspected, or a history of substance abuse. Pregabalin is not known to be active at receptor sites associated with drugs of abuse; however, as with any CNS active drug, physicians should 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).

    Abrupt discontinuation

    Abrupt discontinuation of pregabalin after prolonged use should be avoided to reduce the risk for withdrawal seizures or adverse effects such as insomnia, nausea, headache, anxiety, hyperhidrosis, and diarrhea. Withdraw pregabalin slowly, using a gradual dose-tapering schedule over a minimum of 1 week.

    Renal failure, renal impairment

    Pregabalin should be used with caution in patients with renal impairment or renal failure. Pregabalin is excreted unchanged in the urine and can accumulate with decreased renal function. Dosage adjustments are recommended in patients with renal impairment.

    Chronic obstructive pulmonary disease (COPD), coadministration with other CNS depressants, pulmonary disease, respiratory depression

    Initiate pregabalin at the lowest recommended dose and monitor for symptoms of respiratory depression and sedation in elderly patients, patients with underlying pulmonary disease, such as chronic obstructive pulmonary disease (COPD), and during coadministration with other CNS depressants. Serious, life-threatening, and fatal respiratory depression has been reported with pregabalin. Most cases involved coadministration of another CNS depressant, particularly opioids, in patients with underlying respiratory impairment or advanced age. Respiratory depression, if left untreated, may cause respiratory arrest and death. Management of respiratory depression should include observation, necessary supportive measures, and reduction or withdrawal of CNS depressants, including pregabalin. Taper the dose of pregabalin used for analgesia or seizure control before discontinuation.

    Geriatric

    Initiate pregabalin at the lowest recommended dose and monitor for symptoms of respiratory depression and sedation in geriatric patients. Serious, life-threatening, and fatal respiratory depression has been reported with pregabalin. Most cases involved coadministration of another CNS depressant, particularly opioids, in patients with underlying respiratory impairment or advanced age. Respiratory depression, if left untreated, may cause respiratory arrest and death. Management of respiratory depression should include observation, necessary supportive measures, and reduction or withdrawal of CNS depressants, including pregabalin. Taper the dose of pregabalin used for analgesia or seizure control before discontinuation. Reported clinical trials of pregabalin for epilepsy or neuropathic pain treatment have not revealed significant differences in response between geriatric patients and younger adults. Although the adverse reaction profile was similar between geriatric and younger adult subjects in clinical trials for fibromyalgia, geriatric subjects more frequently reported neurologic reactions such as dizziness, blurred vision, balance disorder, tremor, confusional state, abnormal coordination, and lethargy. Pregabalin is known to be almost exclusively excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Adjust dosing based on estimated creatinine clearance; it may be useful to monitor renal function. According to the Beers Criteria, anticonvulsants are considered potentially inappropriate medications (PIMs) in geriatric patients with a history of falls or fractures and should be avoided in these patient populations, except for treating seizure and mood disorders, since anticonvulsants can produce ataxia, impaired psychomotor function, syncope, and additional falls. If pregabalin must be used, consider reducing the use of other CNS-active medications that increase the risk of falls and fractures and implement strategies to reduce fall risk.[63923] The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities; the use of any anticonvulsant for any condition should be based on confirmation of the condition and its potential cause(s). Determine effectiveness and tolerability by evaluating symptoms, and use these as the basis for dosage adjustment for most patients. Therapeutic drug monitoring is not required or available for most anticonvulsants. Serum medication concentrations (when available) may assist in identifying toxicity. Monitor the treated patient for drug efficacy and side effects. Anticonvulsants can cause a variety of side effects; some adverse reactions can increase the risk of falls. When an anticonvulsant is being used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt periodic tapering of the medication or provide documentation of medical necessity as outlined in the OBRA guidelines.[60742]

    Diabetes mellitus, heart failure

    Pregabalin treatment may cause peripheral edema. Higher frequencies of weight gain and peripheral edema were observed in diabetes mellitus patients taking both pregabalin and a thiazolidinedione antidiabetic agent compared to patients taking either drug alone. As the thiazolidinedione class of antidiabetic drugs can cause weight gain and/or fluid retention, possibly exacerbating or leading to heart failure, exercise caution when coadministering pregabalin and these agents. Because there are limited data on congestive heart failure patients with New York Heart Association (NYHA) Class III or IV cardiac status, exercise caution when using pregabalin in these patients.

    Ocular disease

    In controlled studies, a higher proportion of patients treated with pregabalin reported blurred vision than did patients treated with placebo, which resolved in most cases with continued dosing. Advise patients to notify their health care provider if changes in vision occur. If visual disturbance persists, consider further assessment. Consider more frequent assessment for patients who are already routinely monitored for ocular disease or conditions.

    Labor, obstetric delivery, pregnancy

    There are no adequate and well-controlled studies with pregabalin during pregnancy in women. Pregabalin has been shown to cause animal developmental toxicity (e.g., fetal structural abnormalities and growth retardation) in rats and rabbits given oral pregabalin at doses that produced pregabalin AUC exposures 18 times or more the human exposure at the maximum recommended dose of 660 mg/day. In a study of rats given pregabalin throughout gestation and lactation, offspring growth was reduced at doses of 100 mg/kg or more, and offspring survival decreased at doses of 250 mg/kg or more. When offspring were tested as adults, neurobehavioral abnormalities (i.e., decreased auditory startle response) were observed at doses of 250 mg/kg or more, and decreased fertility and litter size were seen at doses of 1250 mg/kg. The effects of pregabalin on labor and obstetric delivery in pregnant women are unknown. In a prenatal-postnatal study in rats, pregabalin prolonged gestation and induced dystocia at exposures of 50 times or more the mean human exposure. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to pregabalin; information about the registry can be obtained at www.aedpregnancyregistry.org or by calling 1-888-233-2334.

    Breast-feeding

    Breast-feeding is not recommended during treatment with pregabalin due to a potential risk of tumorigenicity. Animal data demonstrate a potential association of tumorigenicity with pregabalin exposure from breast milk, and there is not a clear conclusion regarding the risk from available human clinical studies. Small amounts of pregabalin have been found in the milk of breast-feeding women, with average breast milk steady-state concentrations of approximately 76% of those in maternal plasma. Assuming a mean milk consumption of 150 mL/kg/day, the estimated average daily infant dose of pregabalin from breast-milk was 0.31 mg/kg/day, which would be approximately 7% of the maternal dose. The effects of pregabalin on milk production or the breast-fed infant are unknown.

    Reproductive risk

    Men may experience decreased sperm concentrations and potential reproductive risk with pregabalin therapy. In a randomized, double-blind, placebo-controlled, non-inferiority study to examine the effect of pregabalin on sperm characteristics, healthy male subjects received pregabalin at a daily dose of 600 mg or less (n = 111) or placebo (n = 109) for 13 weeks followed by a 13-week washout period. In the per protocol population (pregabalin, n = 65; placebo, n = 62), approximately 9% of the pregabalin group vs. 3% of the placebo group had a 50% or more reduction in mean sperm concentrations from baseline at week 26. The difference between pregabalin and placebo was within the pre-specified non-inferiority margin of 20%. Sperm concentrations were no longer reduced by 50% or more after an additional 3 months off pregabalin. However, at 9-month and 12-month follow-up visits, 1 subject did demonstrate reductions in sperm concentration of 50% or more. There were no adverse effects on sperm morphology, sperm motility, or serum follicle-stimulating hormone (FSH) or testosterone concentrations vs. placebo. The clinical significance of these data is uncertain.

    ADVERSE REACTIONS

    Severe

    visual impairment / Early / 1.0-5.0
    laryngeal edema / Rapid / 0.1-3.0
    angioedema / Rapid / 0.1-3.0
    heart failure / Delayed / 0.1-1.0
    oliguria / Early / 0.1-1.0
    cholecystitis / Delayed / 0.1-1.0
    pancreatitis / Delayed / 0.1-1.0
    GI bleeding / Delayed / 0.1-1.0
    retinal edema / Delayed / 0.1-1.0
    ocular hemorrhage / Delayed / 0.1-1.0
    suicidal ideation / Delayed / 0.4-0.4
    epididymitis / Delayed / 0-0.1
    coma / Early / 0-0.1
    pulmonary edema / Early / 0-0.1
    renal failure (unspecified) / Delayed / 0-0.1
    increased intracranial pressure / Early / 0-0.1
    pulmonary fibrosis / Delayed / 0-0.1
    apnea / Delayed / 0-0.1
    ventricular fibrillation / Early / 0-0.1
    retroperitoneal fibrosis / Delayed / 0-0.1
    esophageal ulceration / Delayed / 0-0.1
    acute cerebellar syndrome / Early / 0-0.1
    torticollis / Delayed / 0-0.1
    anaphylactoid reactions / Rapid / 0-0.1
    skin atrophy / Delayed / 0-0.1
    exfoliative dermatitis / Delayed / 0-0.1
    Stevens-Johnson syndrome / Delayed / 0-0.1
    skin necrosis / Early / 0-0.1
    papilledema / Delayed / 0-0.1
    keratitis / Delayed / 0-0.1
    night blindness / Delayed / 0-0.1
    optic atrophy / Delayed / 0-0.1
    uveitis / Delayed / 0-0.1
    keratoconjunctivitis / Early / 0-0.1
    Guillain-Barre syndrome / Delayed / 0-0.1
    rhabdomyolysis / Delayed / Incidence not known
    new primary malignancy / Delayed / Incidence not known

    Moderate

    peripheral edema / Delayed / 3.0-27.0
    ataxia / Delayed / 1.0-20.0
    blurred vision / Early / 0.5-12.0
    amblyopia / Delayed / 1.0-12.0
    euphoria / Early / 1.0-12.0
    constipation / Delayed / 0-10.0
    peripheral neuropathy / Delayed / 2.0-9.0
    edema / Delayed / 0.4-8.2
    confusion / Early / 1.0-7.0
    amnesia / Delayed / 0.1-6.0
    myasthenia / Delayed / 1.0-4.9
    chest pain (unspecified) / Early / 0.1-4.0
    memory impairment / Delayed / 1.0-4.0
    myoclonia / Delayed / 1.0-4.0
    fluid retention / Delayed / 2.0-3.0
    hypoglycemia / Early / 1.0-3.0
    dyspnea / Early / 2.0-3.0
    thrombocytopenia / Delayed / 3.0-3.0
    urinary incontinence / Early / 1.0-2.7
    skin ulcer / Delayed / 0.1-2.7
    hypotension / Rapid / 0-2.2
    hypertension / Early / 2.2-2.2
    depression / Delayed / 2.0-2.0
    elevated hepatic enzymes / Delayed / 0.2-1.4
    hematuria / Delayed / 0.1-1.0
    dysuria / Early / 0.1-1.0
    orthostatic hypotension / Delayed / 0.1-1.0
    phlebitis / Rapid / 0.1-1.0
    palpitations / Early / 0.1-1.0
    ejaculation dysfunction / Delayed / 0.1-1.0
    urinary retention / Early / 0.1-1.0
    hyperacusis / Delayed / 0.1-1.0
    oral ulceration / Delayed / 0.1-1.0
    gastritis / Delayed / 0.1-1.0
    colitis / Delayed / 0.1-1.0
    melena / Delayed / 0.1-1.0
    dysphagia / Delayed / 0.1-1.0
    esophagitis / Delayed / 0.1-1.0
    cholelithiasis / Delayed / 0.1-1.0
    hypotonia / Delayed / 0.1-1.0
    hyperalgesia / Delayed / 0.1-1.0
    hyperesthesia / Delayed / 0.1-1.0
    contact dermatitis / Delayed / 0-1.0
    blepharitis / Early / 0.1-1.0
    photophobia / Early / 0.1-1.0
    lymphadenopathy / Delayed / 0.1-1.0
    eosinophilia / Delayed / 0.1-1.0
    anemia / Delayed / 0.1-1.0
    leukopenia / Delayed / 0.1-1.0
    aphasia / Delayed / 0.1-1.0
    dysarthria / Delayed / 0.1-1.0
    hostility / Early / 0.1-1.0
    hallucinations / Early / 0.1-1.0
    proteinuria / Delayed / 0-0.1
    crystalluria / Delayed / 0-0.1
    ascites / Delayed / 0-0.1
    glycosuria / Early / 0-0.1
    cervicitis / Delayed / 0-0.1
    sinus tachycardia / Rapid / 0-0.1
    dyspareunia / Delayed / 0-0.1
    stomatitis / Delayed / 0-0.1
    dyskinesia / Delayed / 0-0.1
    dystonic reaction / Delayed / 0-0.1
    trismus / Delayed / 0-0.1
    neuritis / Delayed / 0-0.1
    exophthalmos / Delayed / 0-0.1
    iritis / Delayed / 0-0.1
    polycythemia / Delayed / 0-0.1
    encephalopathy / Delayed / 0-0.1
    mania / Early / 0-0.1
    delirium / Early / 0-0.1
    psychosis / Early / 0-0.1
    impotence (erectile dysfunction) / Delayed / 0.6
    hypertonia / Delayed / 1.0
    nystagmus / Delayed / 1.0
    conjunctivitis / Delayed / 1.0
    wheezing / Rapid / Incidence not known
    bullous rash / Early / Incidence not known
    myopathy / Delayed / Incidence not known
    physiological dependence / Delayed / Incidence not known
    withdrawal / Early / Incidence not known
    infertility / Delayed / Incidence not known
    respiratory depression / Rapid / Incidence not known

    Mild

    dizziness / Early / 3.4-45.0
    drowsiness / Early / 0.5-35.7
    weight gain / Delayed / 1.0-16.0
    xerostomia / Early / 0.5-15.0
    headache / Early / 1.9-14.0
    infection / Delayed / 3.0-14.0
    diplopia / Early / 0.5-12.0
    fatigue / Early / 1.4-11.0
    tremor / Early / 1.0-11.0
    appetite stimulation / Delayed / 2.0-10.0
    pharyngitis / Delayed / 1.4-8.2
    asthenia / Delayed / 2.0-7.0
    sinusitis / Delayed / 0.4-7.0
    arthralgia / Delayed / 0.7-6.0
    nausea / Early / 1.0-4.9
    lethargy / Early / 4.0-4.0
    hypersalivation / Early / 1.0-4.0
    back pain / Delayed / 1.0-4.0
    vertigo / Early / 1.0-4.0
    insomnia / Early / 3.8-3.8
    flatulence / Early / 1.0-3.0
    vomiting / Early / 1.0-3.0
    hypoesthesia / Delayed / 2.0-3.0
    anxiety / Delayed / 2.0-2.0
    abdominal pain / Early / 0.1-2.0
    diarrhea / Early / 1.0-1.4
    amenorrhea / Delayed / 0.1-1.0
    menorrhagia / Delayed / 0.1-1.0
    leukorrhea / Delayed / 0.1-1.0
    cough / Delayed / 0.2-1.0
    syncope / Early / 0.1-1.0
    dysmenorrhea / Delayed / 0.1-1.0
    chills / Rapid / 0.1-1.0
    pelvic pain / Delayed / 0.1-1.0
    libido increase / Delayed / 0.1-1.0
    dysgeusia / Early / 0.1-1.0
    hyperkinesis / Delayed / 0.1-1.0
    rash / Early / 0.1-1.0
    urticaria / Rapid / 0.1-1.0
    vesicular rash / Delayed / 0.1-1.0
    alopecia / Delayed / 0.1-1.0
    hirsutism / Delayed / 0.1-1.0
    photosensitivity / Delayed / 0.1-1.0
    xerosis / Delayed / 0.1-1.0
    xerophthalmia / Early / 0.1-1.0
    leukocytosis / Delayed / 0.1-1.0
    irritability / Delayed / 0.1-1.0
    malaise / Early / 0.1-1.0
    agitation / Early / 0.1-1.0
    hiccups / Early / 0-0.1
    yawning / Early / 0-0.1
    parosmia / Delayed / 0-0.1
    psychomotor impairment / Early / 0-0.1
    miosis / Early / 0-0.1
    ptosis / Delayed / 0-0.1
    mydriasis / Early / 0-0.1
    purpura / Delayed / 0-0.1
    paranoia / Early / 0-0.1
    orgasm dysfunction / Delayed / 1.0
    muscle cramps / Delayed / 1.0
    increased urinary frequency / Early / 1.0
    myalgia / Early / 1.0
    libido decrease / Delayed / 1.0
    fever / Early / 1.0
    tinnitus / Delayed / 1.0
    paresthesias / Delayed / 1.0
    pruritus / Rapid / 1.0
    ecchymosis / Delayed / 1.0
    breast enlargement / Delayed / Incidence not known
    gynecomastia / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Acetaminophen; Chlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Acetaminophen; Codeine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of doxylamine and pregabalin. Concurrent use may result in additive CNS depression.
    Acetaminophen; Diphenhydramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of diphenhydramine and pregabalin. Concurrent use may result in additive CNS depression.
    Acetaminophen; Hydrocodone: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Acetaminophen; Oxycodone: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of pyrilamine and pregabalin. Concurrent use may result in additive CNS depression.
    Acetaminophen; Pentazocine: (Major) Concomitant use of pentazocine with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of pentazocine with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Acetaminophen; Propoxyphene: (Moderate) Concomitant use of opioid agonists with pregabalin may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Acrivastine; Pseudoephedrine: (Major) Avoid coadministration of acrivastine with pregabalin because of the risk of additive CNS depression. If concurrent use cannot be avoided, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration. Educate patients about the risks and symptoms of excessive CNS depression.
    Alfentanil: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of alfentanil with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The magnitude and duration of CNS and cardiovascular effects of alfentanil may be enhanced. Monitor patients for hypotension or prolonged respiratory depression and sedation. The respiratory depressant effect of alfentanil may persist longer than the measured analgesic effect; consider the total dose of all opioid agonists before ordering opioid analgesics during recovery from anesthesia. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Alogliptin; Pioglitazone: (Moderate) Higher rates of peripheral edema and weight gain may occur in patients who concomitantly use thiazolidinediones with pregabalin. As the thiazolidinediones and pregabalin can both cause weight gain and/or fluid retention, possibly exacerbating or leading to heart failure, care should be taken when co-administering these agents.
    Alprazolam: (Major) Concomitant use of benzodiazepines with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Amitriptyline: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and tricyclic antidepressants. Concomitant use of pregabalin with tricyclic antidepressants may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Amlodipine; Benazepril: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Amobarbital: (Major) Concomitant use of barbiturates with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Amoxapine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and amoxapine. Concomitant use of pregabalin with amoxapine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Amphetamine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
    Amphetamine; Dextroamphetamine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
    Amphetamines: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
    Angiotensin-converting enzyme inhibitors: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Apomorphine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and apomorphine. Concomitant use of pregabalin with apomorphine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as apomorphine, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Aripiprazole: (Moderate) Monitor for excessive sedation and somnolence during coadministration of aripiprazole and pregabalin. Concurrent use may result in additive CNS depression.
    Asenapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of asenapine and pregabalin. Concurrent use may result in additive CNS depression.
    Aspirin, ASA; Butalbital; Caffeine: (Major) Concomitant use of barbiturates with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Concomitant use of barbiturates with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Aspirin, ASA; Caffeine; Orphenadrine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and orphenadrine. Concomitant use of pregabalin with orphenadrine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Aspirin, ASA; Carisoprodol: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and carisoprodol. Concomitant use of pregabalin with carisoprodol may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and carisoprodol. Concomitant use of pregabalin with carisoprodol may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Aspirin, ASA; Oxycodone: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Atropine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of atropine and pregabalin. Concurrent use may result in additive CNS depression.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of atropine and pregabalin. Concurrent use may result in additive CNS depression.
    Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with pregabalin can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. (Moderate) Monitor for excessive sedation and somnolence during coadministration of atropine and pregabalin. Concurrent use may result in additive CNS depression.
    Atropine; Edrophonium: (Moderate) Monitor for excessive sedation and somnolence during coadministration of atropine and pregabalin. Concurrent use may result in additive CNS depression.
    Azelastine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and azelastine. Concomitant use of pregabalin with azelastine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Azelastine; Fluticasone: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and azelastine. Concomitant use of pregabalin with azelastine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Baclofen: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and baclofen. Concomitant use of pregabalin with baclofen may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Barbiturates: (Major) Concomitant use of barbiturates with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Concomitant use of barbiturates with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Belladonna; Opium: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Benazepril: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Benzodiazepines: (Major) Concomitant use of benzodiazepines with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Benzphetamine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
    Brexpiprazole: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and brexpiprazole. Concomitant use of pregabalin with brexpiprazole may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Brompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of brompheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including pregabalin. (Moderate) Monitor for excessive sedation and somnolence during coadministration of brompheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of brompheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of brompheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Brompheniramine; Guaifenesin; Hydrocodone: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of brompheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of brompheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Brompheniramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of brompheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Brompheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of brompheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of brompheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Buprenorphine: (Major) Concomitant use of buprenorphine with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of buprenorphine with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Buprenorphine; Naloxone: (Major) Concomitant use of buprenorphine with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of buprenorphine with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Buspirone: (Moderate) Concomitant administration of pregabalin with CNS depressant drugs, including buspirone, can potentiate the CNS effects of either agent.
    Butabarbital: (Major) Concomitant use of barbiturates with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Butalbital; Acetaminophen: (Major) Concomitant use of barbiturates with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Butalbital; Acetaminophen; Caffeine: (Major) Concomitant use of barbiturates with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of barbiturates with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Butorphanol: (Major) Concomitant use of butorphanol with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of butorphanol with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Calcium, Magnesium, Potassium, Sodium Oxybates: (Major) Concomitant use of sodium oxybate with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and pregabalin. Concurrent use may result in additive CNS depression.
    Capsaicin; Metaxalone: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and metaxalone. Concomitant use of pregabalin with metaxalone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Captopril: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Carbetapentane; Chlorpheniramine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including pregabalin. (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including pregabalin. (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including pregabalin. (Moderate) Monitor for excessive sedation and somnolence during coadministration of diphenhydramine and pregabalin. Concurrent use may result in additive CNS depression.
    Carbetapentane; Guaifenesin: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including pregabalin.
    Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including pregabalin.
    Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including pregabalin.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including pregabalin. (Moderate) Monitor for excessive sedation and somnolence during coadministration of pyrilamine and pregabalin. Concurrent use may result in additive CNS depression.
    Carbetapentane; Pseudoephedrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including pregabalin.
    Carbetapentane; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including pregabalin. (Moderate) Monitor for excessive sedation and somnolence during coadministration of pyrilamine and pregabalin. Concurrent use may result in additive CNS depression.
    Carbidopa; Levodopa: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and levodopa. Concomitant use of pregabalin with levodopa may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as levodopa, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Carbidopa; Levodopa; Entacapone: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and levodopa. Concomitant use of pregabalin with levodopa may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as levodopa, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Carbinoxamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of carbinoxamine and pregabalin. Concurrent use may result in additive CNS depression.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of carbinoxamine and pregabalin. Concurrent use may result in additive CNS depression.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of carbinoxamine and pregabalin. Concurrent use may result in additive CNS depression.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of carbinoxamine and pregabalin. Concurrent use may result in additive CNS depression.
    Carbinoxamine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of carbinoxamine and pregabalin. Concurrent use may result in additive CNS depression.
    Carbinoxamine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of carbinoxamine and pregabalin. Concurrent use may result in additive CNS depression.
    Cariprazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cariprazine and pregabalin. Concurrent use may result in additive CNS depression.
    Carisoprodol: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and carisoprodol. Concomitant use of pregabalin with carisoprodol may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and pregabalin. Concurrent use may result in additive CNS depression.
    Cetirizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cetirizine and pregabalin. Concurrent use may result in additive CNS depression.
    Cetirizine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cetirizine and pregabalin. Concurrent use may result in additive CNS depression.
    Chlophedianol; Dexbrompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of dexbrompheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of dexchlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Chloral Hydrate: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and chloral hydrate. Concomitant use of pregabalin with chloral hydrate may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorcyclizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorcyclizine and pregabalin. Concurrent use may result in additive CNS depression.
    Chlordiazepoxide: (Major) Concomitant use of benzodiazepines with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Chlordiazepoxide; Amitriptyline: (Major) Concomitant use of benzodiazepines with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and tricyclic antidepressants. Concomitant use of pregabalin with tricyclic antidepressants may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlordiazepoxide; Clidinium: (Major) Concomitant use of benzodiazepines with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Chlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Codeine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Dextromethorphan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of chlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Chlorpromazine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and chlorpromazine. Concomitant use of pregabalin with chlorpromazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorthalidone; Clonidine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and clonidine. Concomitant use of pregabalin with clonidine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Chlorzoxazone: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and chlorzoxazone. Concomitant use of pregabalin with chlorzoxazone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Clemastine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of clemastine and pregabalin. Concurrent use may result in additive CNS depression.
    Clobazam: (Major) Concomitant use of clobazam with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Clomipramine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and tricyclic antidepressants. Concomitant use of pregabalin with tricyclic antidepressants may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Clonazepam: (Major) Concomitant use of benzodiazepines with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Clonidine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and clonidine. Concomitant use of pregabalin with clonidine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Clorazepate: (Major) Concomitant use of benzodiazepines with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Clozapine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and clozapine. Concomitant use of pregabalin with clozapine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Codeine; Guaifenesin: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and promethazine. Concomitant use of pregabalin with promethazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Codeine; Promethazine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and promethazine. Concomitant use of pregabalin with promethazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    COMT inhibitors: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and COMT inhibitors. Concomitant use of pregabalin with COMT inhibitors may cause additive CNS depression. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
    Cyclizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cyclizine and pregabalin. Concurrent use may result in additive CNS depression.
    Cyclobenzaprine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and cyclobenzaprine. Concomitant use of pregabalin with cyclobenzaprine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Cyproheptadine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cyproheptadine and pregabalin. Concurrent use may result in additive CNS depression.
    Dantrolene: (Major) Concomitant use of dantrolene with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Desipramine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and tricyclic antidepressants. Concomitant use of pregabalin with tricyclic antidepressants may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Deutetrabenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of deutetrabenazine and pregabalin. Concurrent use may result in additive CNS depression.
    Dexbrompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of dexbrompheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Dexbrompheniramine; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of dexbrompheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Dexchlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of dexchlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of dexchlorpheniramine and pregabalin. Concurrent use may result in additive CNS depression.
    Dexmedetomidine: (Moderate) Monitor for excessive sedation, somnolence, and respiratory depression during coadministration of dexmedetomidine and pregabalin. Concurrent use may result in additive CNS and respiratory depression.
    Dextroamphetamine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of diphenhydramine and pregabalin. Concurrent use may result in additive CNS depression.
    Diazepam: (Major) Concomitant use of benzodiazepines with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Dimenhydrinate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of dimenhydrinate and pregabalin. Concurrent use may result in additive CNS depression.
    Diphenhydramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of diphenhydramine and pregabalin. Concurrent use may result in additive CNS depression.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of diphenhydramine and pregabalin. Concurrent use may result in additive CNS depression.
    Diphenhydramine; Ibuprofen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of diphenhydramine and pregabalin. Concurrent use may result in additive CNS depression.
    Diphenhydramine; Naproxen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of diphenhydramine and pregabalin. Concurrent use may result in additive CNS depression.
    Diphenhydramine; Phenylephrine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of diphenhydramine and pregabalin. Concurrent use may result in additive CNS depression.
    Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with pregabalin can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. (Moderate) Monitor for excessive sedation and somnolence during coadministration of atropine and pregabalin. Concurrent use may result in additive CNS depression.
    Doxepin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and tricyclic antidepressants. Concomitant use of pregabalin with tricyclic antidepressants may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Doxylamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of doxylamine and pregabalin. Concurrent use may result in additive CNS depression.
    Doxylamine; Pyridoxine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of doxylamine and pregabalin. Concurrent use may result in additive CNS depression.
    Dronabinol: (Moderate) Concomitant use of dronabinol with other CNS depressants can potentiate the effects of dronabinol on respiratory depression. Pregabalin can cause considerable somnolence and the combined use of ethanol or other CNS depressants with pregabalin may lead to an additive drowsy effect.
    Droperidol: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and droperidol. Concomitant use of pregabalin with droperidol may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Enalapril, Enalaprilat: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Enalapril; Felodipine: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Esketamine: (Moderate) Closely monitor patients receiving esketamine and pregabalin for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
    Estazolam: (Major) Concomitant use of benzodiazepines with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Eszopiclone: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and eszopiclone. Concomitant use of pregabalin with eszopiclone may cause additive CNS depression and complex sleep-related behaviors (e.g., driving, talking, eating, or performing other activities while not fully awake). Educate patients about the risks and symptoms of excessive CNS depression. Instruct patients to contact their provider immediately if sleep-related symptoms or behaviors occur.
    Ethanol: (Major) Advise patients to avoid alcohol while taking pregabalin. Concomitant use of alcohol with pregabalin may cause excessive sedation, somnolence, and respiratory depression.
    Ezogabine: (Moderate) Due to the CNS effects of ezogabine, an enhanced CNS depressant effect may occur during concurrent use of other centrally-acting medications such as pregabalin. Patients should be monitored for excessive somnolence during concurrent therapy with this agent.
    Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and pregabalin. Concurrent use may result in additive CNS depression.
    Fentanyl: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Flibanserin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of flibanserin and pregabalin. Concurrent use may result in additive CNS depression.
    Fluphenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fluphenazine and pregabalin. Concurrent use may result in additive CNS depression.
    Flurazepam: (Major) Concomitant use of benzodiazepines with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Fosinopril: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Gabapentin: (Major) Concomitant use of gabapentin with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate both pregabalin and gabapentin at the lowest recommended doses and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    General anesthetics: (Major) Concomitant use of general anesthetics with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of excessive respiratory depression. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Glimepiride; Rosiglitazone: (Moderate) Higher rates of peripheral edema and weight gain may occur in patients who concomitantly use thiazolidinediones with pregabalin. As the thiazolidinediones and pregabalin can both cause weight gain and/or fluid retention, possibly exacerbating or leading to heart failure, care should be taken when co-administering these agents.
    Guaifenesin; Hydrocodone: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Guanfacine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of guanfacine and pregabalin. Concurrent use may result in additive CNS depression.
    Haloperidol: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and haloperidol. Concomitant use of pregabalin with haloperidol may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Monitor for excessive sedation and somnolence during coadministration of methyldopa and pregabalin. Concurrent use may result in additive CNS depression.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Hydrocodone: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Hydrocodone; Phenylephrine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Hydrocodone; Potassium Guaiacolsulfonate: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Avoid prescribing opioid cough medications in patients taking pregabalin. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Hydromorphone: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Hydroxychloroquine: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as pregabalin. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Hydroxyzine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and hydroxyzine. Reduce the pregabalin dose by 50% or more when used with hydroxyzine intramuscular injection. Concomitant use of pregabalin with hydroxyzine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Ibuprofen; Oxycodone: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Iloperidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of iloperidone and pregabalin. Concurrent use may result in additive CNS depression.
    Imipramine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and tricyclic antidepressants. Concomitant use of pregabalin with tricyclic antidepressants may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Isocarboxazid: (Moderate) Monitor for excessive sedation and somnolence during coadministration of monoamine oxidase inhibitors (MAOIs) and pregabalin. Concurrent use may result in additive CNS depression. MAOIs can cause a variable change in seizure patterns; therefore, careful monitoring of patients receiving pregabalin for a seizure disorder is required.
    Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and pregabalin. Concurrent use may result in additive CNS depression.
    Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and pregabalin. Dosage adjustments of lemborexant and pregabalin may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
    Levocetirizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cetirizine and pregabalin. Concurrent use may result in additive CNS depression.
    Levodopa: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and levodopa. Concomitant use of pregabalin with levodopa may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as levodopa, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Levorphanol: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Reduce the initial dose of levorphanol by approximately 50% or more. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Lisdexamfetamine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
    Lisinopril: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Lofexidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lofexidine and pregabalin. Concurrent use may result in additive CNS depression.
    Lorazepam: (Major) Concomitant use of benzodiazepines with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Loxapine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of loxapine and pregabalin. Concurrent use may result in additive CNS depression.
    Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and pregabalin. Concurrent use may result in additive CNS depression.
    Lurasidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lurasidone and pregabalin. Concurrent use may result in additive CNS depression.
    Maprotiline: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and maprotiline. Concomitant use of pregabalin with maprotiline may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Meclizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of meclizine and pregabalin. Concurrent use may result in additive CNS depression.
    Melatonin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of melatonin and pregabalin. Concurrent use may result in additive CNS depression.
    Meperidine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Meperidine; Promethazine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and promethazine. Concomitant use of pregabalin with promethazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Mephobarbital: (Major) Concomitant use of barbiturates with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Meprobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of meprobamate and pregabalin. Concurrent use may result in additive CNS depression.
    Metaxalone: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and metaxalone. Concomitant use of pregabalin with metaxalone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Metformin; Rosiglitazone: (Moderate) Higher rates of peripheral edema and weight gain may occur in patients who concomitantly use thiazolidinediones with pregabalin. As the thiazolidinediones and pregabalin can both cause weight gain and/or fluid retention, possibly exacerbating or leading to heart failure, care should be taken when co-administering these agents.
    Methadone: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Methamphetamine: (Moderate) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. Additionally, amphetamines may delay the intestinal absorption of ethosuximide, ethotoin (hydantoin), phenobarbital, and phenytoin, the extent of absorption of these seizure medications is not known to be affected.
    Methocarbamol: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and methocarbamol. Concomitant use of pregabalin with methocarbamol may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Methohexital: (Major) Concomitant use of barbiturates with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Methyldopa: (Moderate) Monitor for excessive sedation and somnolence during coadministration of methyldopa and pregabalin. Concurrent use may result in additive CNS depression.
    Metoclopramide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of metoclopramide and pregabalin. Concurrent use may result in additive CNS depression.
    Midazolam: (Major) Concomitant use of benzodiazepines with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Mirtazapine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and mirtazapine. Concomitant use of pregabalin with mirtazapine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Moexipril: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Molindone: (Moderate) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and molindone. Concomitant use of pregabalin with molindone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Monoamine oxidase inhibitors: (Moderate) Monitor for excessive sedation and somnolence during coadministration of monoamine oxidase inhibitors (MAOIs) and pregabalin. Concurrent use may result in additive CNS depression. MAOIs can cause a variable change in seizure patterns; therefore, careful monitoring of patients receiving pregabalin for a seizure disorder is required.
    Morphine: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Morphine; Naltrexone: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Nabilone: (Moderate) Concomitant use of nabilone with other CNS depressants can potentiate the effects of nabilone on respiratory depression. Pregabalin can cause considerable somnolence and the combined use of ethanol or other CNS depressants with pregabalin may lead to an additive drowsy effect.
    Nalbuphine: (Major) Concomitant use of nalbuphine with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of nalbuphine with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Nefazodone: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and nefazodone. Concomitant use of pregabalin with nefazodone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Nortriptyline: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and tricyclic antidepressants. Concomitant use of pregabalin with tricyclic antidepressants may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Olanzapine: (Moderate) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and olanzapine. Concomitant use of pregabalin with olanzapine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Olanzapine; Fluoxetine: (Moderate) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and olanzapine. Concomitant use of pregabalin with olanzapine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Olanzapine; Samidorphan: (Moderate) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and olanzapine. Concomitant use of pregabalin with olanzapine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Oliceridine: (Major) Concomitant use of oliceridine with pregabalin may cause excessive sedation and somnolence. Limit the use of oliceridine with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
    Orphenadrine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and orphenadrine. Concomitant use of pregabalin with orphenadrine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Oxazepam: (Major) Concomitant use of benzodiazepines with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Oxycodone: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Oxymorphone: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use an initial dose of oxymorphone at 1/3 to 1/2 the usual dosage and titrate to clinical response. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Paliperidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of paliperidone and pregabalin. Concurrent use may result in additive CNS depression.
    Pentazocine: (Major) Concomitant use of pentazocine with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of pentazocine with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Pentazocine; Naloxone: (Major) Concomitant use of pentazocine with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of pentazocine with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Pentobarbital: (Major) Concomitant use of barbiturates with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Perampanel: (Moderate) Monitor for excessive sedation and somnolence during coadministration of perampanel and pregabalin. Concurrent use may result in additive CNS depression.
    Perindopril: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Perindopril; Amlodipine: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Perphenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of perphenazine and pregabalin. Concurrent use may result in additive CNS depression.
    Perphenazine; Amitriptyline: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and tricyclic antidepressants. Concomitant use of pregabalin with tricyclic antidepressants may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of perphenazine and pregabalin. Concurrent use may result in additive CNS depression.
    Phenelzine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of monoamine oxidase inhibitors (MAOIs) and pregabalin. Concurrent use may result in additive CNS depression. MAOIs can cause a variable change in seizure patterns; therefore, careful monitoring of patients receiving pregabalin for a seizure disorder is required.
    Phenobarbital: (Major) Concomitant use of barbiturates with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Concomitant use of barbiturates with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of atropine and pregabalin. Concurrent use may result in additive CNS depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of scopolamine and pregabalin. Concurrent use may result in additive CNS depression.
    Phentermine; Topiramate: (Moderate) Concurrent use of topiramate and drugs that cause thrombocytopenia such as the anticonvulsant pregabalin, may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation.
    Pimavanserin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of pimavanserin and pregabalin. Concurrent use may result in additive CNS depression.
    Pimozide: (Moderate) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and pimozide. Concomitant use of pregabalin with pimozide may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Pioglitazone: (Moderate) Higher rates of peripheral edema and weight gain may occur in patients who concomitantly use thiazolidinediones with pregabalin. As the thiazolidinediones and pregabalin can both cause weight gain and/or fluid retention, possibly exacerbating or leading to heart failure, care should be taken when co-administering these agents.
    Pioglitazone; Glimepiride: (Moderate) Higher rates of peripheral edema and weight gain may occur in patients who concomitantly use thiazolidinediones with pregabalin. As the thiazolidinediones and pregabalin can both cause weight gain and/or fluid retention, possibly exacerbating or leading to heart failure, care should be taken when co-administering these agents.
    Pioglitazone; Metformin: (Moderate) Higher rates of peripheral edema and weight gain may occur in patients who concomitantly use thiazolidinediones with pregabalin. As the thiazolidinediones and pregabalin can both cause weight gain and/or fluid retention, possibly exacerbating or leading to heart failure, care should be taken when co-administering these agents.
    Pramipexole: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and pramipexole. Concomitant use of pregabalin with pramipexole may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as pramipexole, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Primidone: (Major) Concomitant use of barbiturates with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Prochlorperazine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and prochlorperazine. Concomitant use of pregabalin with prochlorperazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Concurrent administration of prochlorperazine is contraindicated in patients receiving large doses of CNS depressants.
    Promethazine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and promethazine. Concomitant use of pregabalin with promethazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Promethazine; Dextromethorphan: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and promethazine. Concomitant use of pregabalin with promethazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Promethazine; Phenylephrine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and promethazine. Concomitant use of pregabalin with promethazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Propoxyphene: (Moderate) Concomitant use of opioid agonists with pregabalin may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
    Protriptyline: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and tricyclic antidepressants. Concomitant use of pregabalin with tricyclic antidepressants may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Pseudoephedrine; Triprolidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of triprolidine and pregabalin. Concurrent use may result in additive CNS depression.
    Pyrilamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of pyrilamine and pregabalin. Concurrent use may result in additive CNS depression.
    Quazepam: (Major) Concomitant use of benzodiazepines with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Quetiapine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and quetiapine. Concomitant use of pregabalin with quetiapine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Quinapril: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Ramelteon: (Moderate) Monitor for excessive sedation and somnolence during coadministration of ramelteon and pregabalin. Concurrent use may result in additive CNS depression.
    Ramipril: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Rasagiline: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and rasagiline. Concomitant use of pregabalin with rasagiline may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as rasagiline, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Remifentanil: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of remifentanil with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Remimazolam: (Major) Concomitant use of benzodiazepines with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Risperidone: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and risperidone. Concomitant use of pregabalin with risperidone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Ropinirole: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and ropinirole. Concomitant use of pregabalin with ropinirole may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as ropinirole, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Rosiglitazone: (Moderate) Higher rates of peripheral edema and weight gain may occur in patients who concomitantly use thiazolidinediones with pregabalin. As the thiazolidinediones and pregabalin can both cause weight gain and/or fluid retention, possibly exacerbating or leading to heart failure, care should be taken when co-administering these agents.
    Rotigotine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and rotigotine. Concomitant use of pregabalin with rotigotine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as rotigotine, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Safinamide: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and safinamide. Concomitant use of pregabalin with safinamide may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as safinamide, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
    Scopolamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of scopolamine and pregabalin. Concurrent use may result in additive CNS depression.
    Secobarbital: (Major) Concomitant use of barbiturates with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Selegiline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and pregabalin. Concurrent use may result in additive CNS depression.
    Sodium Oxybate: (Major) Concomitant use of sodium oxybate with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Sufentanil: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of sufentanil with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of sufentanil with CNS depressants may result in decreased pulmonary artery pressure and hypotension. As postoperative analgesia, concomitant use increases the risk for hypotension, respiratory depression, profound sedation, coma, and death. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Suvorexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of suvorexant and pregabalin. Concurrent use may result in additive CNS depression.
    Tapentadol: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Tasimelteon: (Moderate) Monitor for excessive sedation and somnolence during coadministration of tasimelteon and pregabalin. Concurrent use may result in additive CNS depression.
    Temazepam: (Major) Concomitant use of benzodiazepines with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Tetrabenazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of tetrabenazine and pregabalin. Concurrent use may result in additive CNS depression.
    Thalidomide: (Major) Avoid coadministration of thalidomide with pregabalin because of the risk of additive CNS depression. If concurrent use cannot be avoided, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration. Educate patients about the risks and symptoms of excessive CNS depression.
    Thiazolidinediones: (Moderate) Higher rates of peripheral edema and weight gain may occur in patients who concomitantly use thiazolidinediones with pregabalin. As the thiazolidinediones and pregabalin can both cause weight gain and/or fluid retention, possibly exacerbating or leading to heart failure, care should be taken when co-administering these agents.
    Thiopental: (Major) Concomitant use of barbiturates with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Thioridazine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and thioridazine. Concomitant use of pregabalin with thioridazine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Thiothixene: (Moderate) Monitor for excessive sedation and somnolence during coadministration of thiothixene and pregabalin. Concurrent use may result in additive CNS depression.
    Tizanidine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and tizanidine. Concomitant use of pregabalin with tizanidine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Topiramate: (Moderate) Concurrent use of topiramate and drugs that cause thrombocytopenia such as the anticonvulsant pregabalin, may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation.
    Tramadol: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Tramadol; Acetaminophen: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Trandolapril: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Trandolapril; Verapamil: (Moderate) Concomitant use of pregabalin with angiotensin converting enzyme (ACE) inhibitors should be closely monitored. Life-threatening angioedema with respiratory compromise has been reported with use of pregabalin. Angioedema of the face, mouth (lips, tongue, gums), throat, and larynx has occurred. The risk of developing this complication may be increased when pregabalin is used with ACE inhibitors or other drugs known to cause angioedema.
    Tranylcypromine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of monoamine oxidase inhibitors (MAOIs) and pregabalin. Concurrent use may result in additive CNS depression. MAOIs can cause a variable change in seizure patterns; therefore, careful monitoring of patients receiving pregabalin for a seizure disorder is required.
    Trazodone: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and trazodone. Concomitant use of pregabalin with trazodone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Triazolam: (Major) Concomitant use of benzodiazepines with pregabalin may cause excessive sedation, somnolence, and respiratory depression. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression.
    Tricyclic antidepressants: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and tricyclic antidepressants. Concomitant use of pregabalin with tricyclic antidepressants may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Trifluoperazine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of trifluoperazine and pregabalin. Concurrent use may result in additive CNS depression.
    Trimipramine: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and tricyclic antidepressants. Concomitant use of pregabalin with tricyclic antidepressants may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Triprolidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of triprolidine and pregabalin. Concurrent use may result in additive CNS depression.
    Valerian, Valeriana officinalis: (Moderate) Monitor for excessive sedation and somnolence during coadministration of valerian and pregabalin. Concurrent use may result in additive CNS depression.
    Valproic Acid, Divalproex Sodium: (Moderate) Monitor for excessive sedation and somnolence during coadministration of valproic acid and pregabalin. Concurrent use may result in additive CNS depression.
    Zaleplon: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and zaleplon. Concomitant use of pregabalin with zaleplon may cause additive CNS depression and complex sleep-related behaviors (e.g., driving, talking, eating, or performing other activities while not fully awake). Educate patients about the risks and symptoms of excessive CNS depression. Instruct patients to contact their provider immediately if sleep-related symptoms or behaviors occur.
    Ziprasidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of ziprasidone and pregabalin. Concurrent use may result in additive CNS depression.
    Zolpidem: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and zolpidem. The recommended dose of sublingual zolpidem tablets is 1.75 mg/night in patients receiving concomitant CNS depressants. Concomitant use of pregabalin with zolpidem may cause additive CNS depression and complex sleep-related behaviors (e.g., driving, talking, eating, or performing other activities while not fully awake). Educate patients about the risks and symptoms of excessive CNS depression. Instruct patients to contact their provider immediately if sleep-related symptoms or behaviors occur.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate and well-controlled studies with pregabalin during pregnancy in women. Pregabalin has been shown to cause animal developmental toxicity (e.g., fetal structural abnormalities and growth retardation) in rats and rabbits given oral pregabalin at doses that produced pregabalin AUC exposures 18 times or more the human exposure at the maximum recommended dose of 660 mg/day. In a study of rats given pregabalin throughout gestation and lactation, offspring growth was reduced at doses of 100 mg/kg or more, and offspring survival decreased at doses of 250 mg/kg or more. When offspring were tested as adults, neurobehavioral abnormalities (i.e., decreased auditory startle response) were observed at doses of 250 mg/kg or more, and decreased fertility and litter size were seen at doses of 1250 mg/kg. The effects of pregabalin on labor and obstetric delivery in pregnant women are unknown. In a prenatal-postnatal study in rats, pregabalin prolonged gestation and induced dystocia at exposures of 50 times or more the mean human exposure. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to pregabalin; information about the registry can be obtained at www.aedpregnancyregistry.org or by calling 1-888-233-2334.

    MECHANISM OF ACTION

    Pregabalin is a structural analogue of gamma-aminobutyric acid (GABA) and has anxiolytic, analgesic, and antiepileptic properties. Pregabalin is structurally related to gabapentin, but pregabalin has shown greater potency than gabapentin in pain and seizure disorders (3- to 10-times more potent in animal studies). The exact mechanism of action of pregabalin as an antiseizure agent has not been determined. Pregabalin does not show direct GABA-mimetic effects, but increases neuronal GABA levels as well as produces a dose-dependent increase in glutamic acid decarboxylase activity. Pregabalin reduces neuronal calcium currents by binding to the alpha-2-delta subunit of calcium channels, and this particular mechanism may be responsible for effects in neuropathic pain, anxiety, and other pain syndromes. Pregabalin does not bind directly to GABAA, GABAB, or benzodiazepine receptors, 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.

    PHARMACOKINETICS

    Pregabalin is administered orally. Pregabalin does not bind to plasma proteins and shows negligible hepatic metabolism. The volume of distribution is 0.5 L/kg. Although human data are not available, pregabalin has been shown to cross into the blood-brain barrier, placenta, and breast milk in animal studies. The primary route of elimination is renal excretion, with 90% to 98% of an administered dose eliminated unchanged in the urine. Pregabalin clearance by the kidneys is directly proportional to CrCl in patients not on dialysis. Mean renal clearance is roughly 67 to 81 mL/minute in young, healthy subjects. Because pregabalin is not bound to plasma proteins, this clearance rate indicates that renal tubular reabsorption is involved. Pregabalin undergoes minimal metabolism. The elimination half-life has been reported to be roughly 6 hours.
     
    Affected cytochrome P450 isoenzymes: none
    In vitro studies suggest that pregabalin does not inhibit CYP isoenzymes including 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 or induce isoenzymes 1A2 or 3A4.

    Oral Route

    Oral bioavailability of pregabalin is roughly 90% and is independent of dose. Oral formulations are rapidly absorbed. The immediate-release oral solution and capsules are bioequivalent dissolving at a rate of more than 85% within 30 minutes. Pregabalin displays linear pharmacokinetics. The median Tmax for immediate-release formulations is 0.7 hours (0.7 to 1.5 hours), and for extended-release tablets is 8 hours (5 to 12 hours). After multiple oral doses, steady state concentrations are achieved within 1 to 2 days for immediate-release formulations and 2 to 3 days for extended-release formulations. Food delays the rate but not the extent of absorption of immediate-release formulations. Administration of the extended-release tablets once daily after an evening meal has an equivalent AUC and lower Cmax compared to administration of immediate-release formulations without food twice daily.