Lyrica CR

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Lyrica CR

Classes

Anticonvulsants, Gabapentinoids
Neuropathic Pain and Peripheral Neuropathy Agents

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.

Adverse Reactions
Severe

visual impairment / Early / 1.0-5.0
laryngeal edema / Rapid / 0.1-3.0
angioedema / Rapid / 0.1-3.0
oliguria / Early / 0.1-1.0
heart failure / Delayed / 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
renal failure (unspecified) / Delayed / 0-0.1
apnea / Delayed / 0-0.1
coma / Early / 0-0.1
increased intracranial pressure / Early / 0-0.1
pulmonary edema / Early / 0-0.1
pulmonary fibrosis / Delayed / 0-0.1
retroperitoneal fibrosis / Delayed / 0-0.1
ventricular fibrillation / Early / 0-0.1
laryngospasm / Rapid / 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
dysuria / Early / 0.1-1.0
ejaculation dysfunction / Delayed / 0.1-1.0
hematuria / Delayed / 0.1-1.0
urinary retention / Early / 0.1-1.0
hyperacusis / Delayed / 0.1-1.0
orthostatic hypotension / Delayed / 0.1-1.0
phlebitis / Rapid / 0.1-1.0
palpitations / Early / 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
hyperalgesia / Delayed / 0.1-1.0
hypotonia / 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
cervicitis / Delayed / 0-0.1
dyspareunia / Delayed / 0-0.1
ascites / Delayed / 0-0.1
crystalluria / Delayed / 0-0.1
glycosuria / Early / 0-0.1
proteinuria / Delayed / 0-0.1
sinus tachycardia / Rapid / 0-0.1
balanitis / Delayed / 0-0.1
stomatitis / Delayed / 0-0.1
dyskinesia / Delayed / 0-0.1
neuritis / Delayed / 0-0.1
trismus / Delayed / 0-0.1
dystonic reaction / 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
dysmenorrhea / Delayed / 0.1-1.0
leukorrhea / Delayed / 0.1-1.0
menorrhagia / Delayed / 0.1-1.0
chills / Rapid / 0.1-1.0
libido increase / Delayed / 0.1-1.0
pelvic pain / Delayed / 0.1-1.0
syncope / Early / 0.1-1.0
cough / Delayed / 0.2-1.0
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
parosmia / Delayed / 0-0.1
hiccups / Early / 0-0.1
yawning / Early / 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
increased urinary frequency / Early / 1.0
libido decrease / Delayed / 1.0
muscle cramps / Delayed / 1.0
myalgia / Early / 1.0
orgasm dysfunction / Delayed / 1.0
tinnitus / Delayed / 1.0
fever / Early / 1.0
paresthesias / Delayed / 1.0
pruritus / Rapid / 1.0
ecchymosis / Delayed / 1.0
musculoskeletal pain / Early / Incidence not known
breast enlargement / Delayed / Incidence not known
gynecomastia / Delayed / Incidence not known

Common Brand Names

Lyrica, Lyrica CR

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, and fibromyalgia in adults and adjunctive therapy for partial onset seizures in adult and pediatric patients
Monitor for emerging or worsening depression, suicidal thoughts/behavior, or mood/behavior changes

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

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

Adolescents 17 years

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

Children and Adolescents 4 to 16 years weighing 30 kg or more

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

Infants and Children 1 month to 3 years

3.5 mg/kg/day PO divided 3 times daily, 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 neuropathic pain due to diabetic neuropathy, postherpetic neuralgia, spinal cord injury, and trigeminal neuralgia†. For the treatment of peripheral diabetic neuropathy. 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 due to 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 treatment of trigeminal neuralgia†. Oral dosage (immediate-release) Adults

75 mg PO twice daily for 1 week, then 150 mg PO twice daily for 1 week, then 300 mg PO twice daily.

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

50 mg PO twice daily for 2 days, then 100 mg PO twice daily for 2 days, and then 150 mg PO twice daily, initially, or alternately, 75 mg PO twice daily, initially; may increase the dose by 150 mg/day at weekly intervals as needed. Usual dose: 150 to 600 mg/day in 2 to 3 divided doses. Max: 600 mg/day.

†Indicates off-label use

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

Adult patients
CrCl 60 mL/minute or more: No dose adjustment needed.
CrCl 30 to 60 mL/minute: 75 to 300 mg/day PO divided 2 or 3 times daily for immediate-release formulations; reduce dose by 50% for extended-release tablets.
CrCl 15 to 30 mL/minute: 25 to 150 mg/day PO divided once or twice daily for immediate-release formulations. Use of the extended-release tablet is not recommended.
CrCl 15 mL/minute or less: 25 to 75 mg PO once daily for immediate-release formulations. Use of the extended-release tablet is not recommended.
 
Pediatric patients
Based on pharmacokinetic modeling, the following maximum daily doses have been recommended in pediatric patients with renal impairment:
Pediatric patients weighing 30 kg or more
CrCl 60 mL/minute/1.73 m2 or more: No dose adjustment needed.
CrCl 30 to 60 mL/minute/1.73 m2: 5 mg/kg/day PO divided twice daily
CrCl 15 to 30 mL/minute/1.73 m2: 2.5 mg/kg/day PO divided twice daily.
CrCl less than 15 mL/minute/1.73 m2: 1 mg/kg/day PO divided once or twice daily.
 
Pediatric patients weighing less than 30 kg
CrCl 60 mL/minute/1.73 m2 or more: No dose adjustment needed.
CrCl 30 to 60 mL/minute/1.73 m2: 7 mg/kg/day PO divided twice daily.
CrCl 15 to 30 mL/minute/1.73 m2: 3.5 mg/kg/day PO divided twice daily.
CrCl less than 15 mL/minute/1.73 m2: 1.4 mg/kg/day PO divided once or twice daily.
 
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 3 times weekly hemodialysis, who were administered pregabalin roughly 24 hours prior to next scheduled dialysis session. For patients undergoing hemodialysis, adjust the pregabalin daily dose based on renal function. In addition to the daily dose adjustment, give a supplemental dose immediately after every 4-hour hemodialysis treatment.
Adult patients
For patients receiving the 25 mg once daily regimen: 1 supplemental dose of 25 or 50 mg
For patients receiving the 25 to 50 mg once daily regimen: 1 supplemental dose of 50 or 75 mg
For patients receiving 50 to 75 mg once daily regimen: 1 supplemental dose of 75 or 100 mg
For patients receiving the 75 mg once daily regimen: 1 supplemental dose of 100 or 150 mg
 
Pediatric patients
Pediatric-specific recommendations are not available.

Drug Interactions

Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of diphenhydramine and pregabalin. Concurrent use may result in additive CNS depression.
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; Caffeine; Pyrilamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of pyrilamine and pregabalin. Concurrent use may result in additive CNS 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; 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.
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) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing 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.
Angiotensin-converting enzyme inhibitors: (Moderate) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing 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 respiratory depression and sedation during concomitant aripiprazole and pregabalin use; consider starting pregabalin at a low dose. Concomitant use increases the risk for 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; 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; 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; 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.
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; 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) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing angioedema.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing 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.
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; Dextromethorphan; Phenylephrine: (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.
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.
Butalbital; Aspirin; 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) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing angioedema.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing angioedema.
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.
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.
Celecoxib; 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.
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 unusual drowsiness and sedation during coadministration of cetirizine and pregabalin due to the risk for additive CNS depression.
Cetirizine; Pseudoephedrine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and pregabalin due to the risk for 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.
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; 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; 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.
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.
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.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
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; 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) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing angioedema.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing 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 consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
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.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Fosinopril: (Moderate) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing angioedema.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing 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.
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.
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; Moexipril: (Moderate) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing 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; 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) Monitor persons with epilepsy for seizure activity during concomitant pregabalin and hydroxychloroquine use. 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 respiratory depression and sedation during concomitant monoamine oxidase inhibitor (MAOI) and pregabalin use; consider starting pregabalin at a low dose. Concomitant use increases the risk for additive CNS depression.
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 unusual drowsiness and sedation during coadministration of cetirizine and pregabalin due to the risk for 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 o

f 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.
Lisinopril: (Moderate) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing angioedema.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing 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.
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.
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.
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) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing 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 respiratory depression and sedation during concomitant monoamine oxidase inhibitor (MAOI) and pregabalin use; consider starting pregabalin at a low dose. Concomitant use increases the risk for additive CNS depression.
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) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing angioedema.
Perindopril; Amlodipine: (Moderate) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing 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 respiratory depression and sedation during concomitant monoamine oxidase inhibitor (MAOI) and pregabalin use; consider starting pregabalin at a low dose. Concomitant use increases the risk for additive CNS depression.
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) Monitor for respiratory depression and sedation during concomitant topiramate and pregabalin use; consider starting pregabalin at a low dose. Concomitant use increases the risk for additive CNS depression.
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.
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.
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) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing angioedema.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing 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) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing 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.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and pregabalin. Concurrent use may result in additive CNS 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.
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) Monitor for respiratory depression and sedation during concomitant topiramate and pregabalin use; consider starting pregabalin at a low dose. Concomitant use increases the risk for additive CNS depression.
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) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing angioedema.
Trandolapril; Verapamil: (Moderate) Monitor for signs and symptoms of angioedema during concomitant angiotensin-converting enzyme inhibitor and pregabalin use. Concomitant use may increase the risk of developing angioedema.
Tranylcypromine: (Moderate) Monitor for respiratory depression and sedation during concomitant monoamine oxidase inhibitor (MAOI) and pregabalin use; consider starting pregabalin at a low dose. Concomitant use increases the risk for additive CNS depression.
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.
Zuranolone: (Major) Avoid the use of multiple sedating agents due to the risk for additive CNS depression. If use is necessary, consider a downward dosage adjustment of either or both medications, especially in patients with additional risk factors for sedation-related harm.

How Supplied

Lyrica CR/Pregabalin 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

Maximum Dosage
Adults

600 mg/day PO for immediate-release formulations; 660 mg/day PO for extended-release tablets.

Geriatric

600 mg/day PO for immediate-release formulations; 660 mg/day PO for extended-release tablets.

Adolescents

17 years: 600 mg/day PO for immediate-release formulations.
13 to 16 years weighing 30 kg or more: 10 mg/kg/day PO (Max: 600 mg/day) for immediate-release formulations.
13 to 16 years weighing less than 30 kg: 14 mg/kg/day PO for immediate-release formulations.

Children

weighing 30 kg or more: 10 mg/kg/day PO (Max: 600 mg/day) for immediate-release formulations.
weighing less than 30 kg: 14 mg/kg/day PO for immediate-release formulations.

Infants

14 mg/kg/day PO for immediate-release formulations.

Neonates

Safety and efficacy have not been established.

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 opioid 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. Pregabalin has been shown to cross into the blood-brain barrier and placenta in animal studies. Small amounts of pregabalin have been detected in the breast milk of lactating women. 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.

Pregnancy And Lactation
Pregnancy

Data from observational studies of pregabalin use during human pregnancy suggest a possible small increase in the incidence of overall major birth defects; there was no consistent or specific pattern of major birth defects identified. A database study reported a prevalence ratio for major malformations overall of 1.14 (95% CI: 0.96 to 1.35) for 2,700 pregnancies exposed to pregabalin monotherapy during the first trimester compared to 3,063,251 pregnancies not exposed to antiepileptic drugs (AEDs). Study limitations include the inability to control for underlying disease states or other potential confounders, in addition to a lack of verification of compliance with the AED regimen. A second database study showed no increase in the risk of major birth defects for 353 pregnancies with first trimester pregabalin monotherapy exposure when compared to 368,489 pregnancies with no AED exposure (adjusted relative risk 0.87 [95% CI 0.53 to 1.42]). A third database study suggested a small increase in the risk of major birth defects for 118 pregnancies with first trimester pregabalin monotherapy exposure when compared to 380,347 pregnancies with no AED exposure (adjusted relative risk 1.26 [95% CI 0.64 to 2.49]). Limitations consistent with previous database studies were present. Available postmarketing data on miscarriage and other maternal, fetal, and long-term developmental adverse effects were insufficient to identify risk associated with pregabalin. 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 1,250 mg/kg. 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 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.