Pregabalin

Drug overview for PREGABALIN (pregabalin):

Generic name: PREGABALIN (pree-GAH-ba-lin)
Drug class: Anticonvulsants
Therapeutic class: Central Nervous System Agents

Pregabalin is an anticonvulsant structurally related to the inhibitory CNS neurotransmitter gamma-aminobutyric acid (GABA); the drug also possesses analgesic activity.

No enhanced Uses information available for this drug.

DRUG IMAGES

PREGABALIN 100 MG CAPSULE
PREGABALIN 225 MG CAPSULE
PREGABALIN 25 MG CAPSULE
PREGABALIN 50 MG CAPSULE
PREGABALIN 75 MG CAPSULE
PREGABALIN 150 MG CAPSULE
PREGABALIN 200 MG CAPSULE
PREGABALIN 300 MG CAPSULE

The following indications for PREGABALIN (pregabalin) have been approved by the FDA:

Indications:
Diabetic peripheral neuropathy
Fibromyalgia
Neuropathic pain associated with spinal cord injury
Partial epilepsy treatment adjunct
Postherpetic neuralgia

Professional Synonyms:
Diabetic neuropathy
Fibromyalgia syndrome
Partial onset seizures treatment adjunct
Partial seizures treatment adjunct
Post herpetic neuralgia
Postherpetic neurodynia
Spinal cord injury related neuropathic pain

The following dosing information is available for PREGABALIN (pregabalin):

Dosing
Administration
PREGABALIN
PREGABALIN

No enhanced Dosing information available for this drug.

Pregabalin is administered orally as conventional (immediate-release) capsules or oral solution. The drug also is available as extended-release tablets for the treatment of postherpetic neuralgia (PHN) or diabetic peripheral neuropathy (DPN) in adults; efficacy of this preparation has not been established for other indications. Pregabalin capsules and oral solution are administered orally without regard to food; the extended-release tablets should be administered once daily after the evening meal.

The extended-release tablets should be swallowed whole and not split, crushed, or chewed. When switching from conventional preparations of pregabalin to the extended-release tablets, patients should take their usual morning dose of conventional capsules or oral solution, and initiate therapy with the extended-release tablets after the evening meal. The appropriate dose conversion should be performed according to the table below (see Table 1).

Table 1. Dose Conversion from Conventional to Extended-release Pregabalin Conventional Pregabalin Total Daily Extended-release Pregabalin Dose Dose 75 mg daily (given 2 or 3 times 82.5 mg once daily daily) 150 mg daily (given 2 or 3 times 165 mg once daily daily) 225 mg daily (given 2 or 3 times 247.5 mg once daily daily) 300 mg daily (given 2 or 3 times 330 mg once daily daily) 450 mg daily (given 2 or 3 times 495 mg once daily daily) 600 mg daily (given 2 or 3 times 660 mg once daily daily) When discontinuing therapy, pregabalin should be withdrawn gradually by tapering the dosage over at least 1 week. (See Discontinuance of Therapy under Cautions: Warnings/Precautions.) Patients currently receiving or beginning therapy with pregabalin and/or any other anticonvulsant for any indication should be closely monitored for the emergence or worsening of depression, suicidal thoughts or behavior (suicidality), and/or any unusual changes in mood or behavior. (See Suicidality Risk under Cautions: Warnings/Precautions.)

Dosing information for PREGABALIN
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
PREGABALIN 25 MG CAPSULE	Maintenance	Adults take 1 capsule (25 mg) by oral route 3 times per day
PREGABALIN 50 MG CAPSULE	Maintenance	Adults take 1 capsule (50 mg) by oral route 3 times per day
PREGABALIN 75 MG CAPSULE	Maintenance	Adults take 1 capsule (75 mg) by oral route 2 times per day
PREGABALIN 100 MG CAPSULE	Maintenance	Adults take 1 capsule (100 mg) by oral route 3 times per day
PREGABALIN 150 MG CAPSULE	Maintenance	Adults take 1 capsule (150 mg) by oral route 2 times per day
PREGABALIN 200 MG CAPSULE	Maintenance	Adults take 1 capsule (200 mg) by oral route 3 times per day
PREGABALIN 225 MG CAPSULE	Maintenance	Adults take 1 capsule (225 mg) by oral route 2 times per day
PREGABALIN 300 MG CAPSULE	Maintenance	Adults take 1 capsule (300 mg) by oral route 2 times per day

Generic dosing information for PREGABALIN
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
PREGABALIN 25 MG CAPSULE	Maintenance	Adults take 1 capsule (25 mg) by oral route 3 times per day
PREGABALIN 50 MG CAPSULE	Maintenance	Adults take 1 capsule (50 mg) by oral route 3 times per day
PREGABALIN 75 MG CAPSULE	Maintenance	Adults take 1 capsule (75 mg) by oral route 2 times per day
PREGABALIN 100 MG CAPSULE	Maintenance	Adults take 1 capsule (100 mg) by oral route 3 times per day
PREGABALIN 150 MG CAPSULE	Maintenance	Adults take 1 capsule (150 mg) by oral route 2 times per day
PREGABALIN 200 MG CAPSULE	Maintenance	Adults take 1 capsule (200 mg) by oral route 3 times per day
PREGABALIN 225 MG CAPSULE	Maintenance	Adults take 1 capsule (225 mg) by oral route 2 times per day
PREGABALIN 300 MG CAPSULE	Maintenance	Adults take 1 capsule (300 mg) by oral route 2 times per day

The following drug interaction information is available for PREGABALIN (pregabalin):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 3 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Sodium Oxybate/Agents that May Cause Respiratory Depression SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Oxybate by itself may be associated with severe somnolence or respiratory depression. Concurrent use with other CNS depressants may further increase the risk for respiratory depression or loss of consciousness.(1-3) CLINICAL EFFECTS: Concurrent use of sodium oxybate and sedative hypnotics or alcohol may further increase the risk for profound sedation, respiratory depression, coma, and/or death.(1,2) Fatalities have been reported.(3) PREDISPOSING FACTORS: Based upon FDA evaluation of deaths in patients taking sodium oxybate, risk factors may include: use of multiple drugs which depress the CNS, more rapid than recommended oxybate dose titration, exceeding the maximum recommended oxybate dose, and prescribing for unapproved uses such as fibromyalgia, insomnia or migraine. Note that in oxybate clinical trials for narcolepsy 78% - 85% of patients were also receiving concomitant CNS stimulants.(1-3) PATIENT MANAGEMENT: Avoid use of concomitant opioids, benzodiazepines, sedating antidepressants, sedating antipsychotics, general anesthetics, or muscle relaxants, particularly when predisposing risk factors are present. If combination use is required, dose reduction or discontinuation of one or more CNS depressants should be considered. If short term use of an opioid or general anesthetic is required, consider interruption of sodium oxybate treatment.(1,2) Respiratory depression can occur at any time during opioid therapy, especially during therapy initiation and following dosage increases. Consider this risk when using concurrently with other agents that may cause CNS depression.(4) Discuss naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing naloxone to patients prescribed medicines to treat OUD or opioid analgesics (such as those taking CNS depressants) who are at increased risk of opioid overdose and when a patient has household members/close contacts at risk for accidental overdose.(5) DISCUSSION: The FDA evaluated sodium oxybate postmarket fatal adverse event reports from the FDA Adverse Event Reporting System(AERS)and from the manufacturer. Although report documentation was not always optimal or complete, useful information was obtained. Factors which may have contributed to fatal outcome: concomitant use of one or more drugs which depress the CNS, more rapid than recommended oxybate dose titration, exceeding the maximum recommended oxybate dose, and prescribing for unapproved uses such as fibromyalgia, insomnia or migraine. Many deaths occurred in patients with serious psychiatric disorders such as depression and substance abuse. Other concomitant diseases may have also contributed to respiratory and CNS depressant effects of oxybate.(3)	LUMRYZ, LUMRYZ STARTER PACK, SODIUM OXYBATE, XYREM, XYWAV
Gabapentinoids/Opioids (Cough & Cold) SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Opioid-induced reduction in GI motility may increase the absorption of gabapentin and pregabalin.(1) Gabapentin and pregabalin may reverse opioid-induced tolerance of respiratory depression.(2) Concurrent use may result in profound sedation, respiratory depression, coma, and/or death.(3) CLINICAL EFFECTS: Concurrent use of opioids may result in elevated levels of and toxicity from gabapentin and pregabalin, including profound sedation, respiratory depression, coma, and/or death.(1-7) PREDISPOSING FACTORS: Patients who are elderly, are taking other CNS depressants, have decreased renal function, and/or have conditions that reduce lung function (e.g. Chronic Obstructive Pulmonary Disease [COPD]) may be at a higher risk of this interaction. PATIENT MANAGEMENT: Avoid prescribing opioid-including cough medications for patients taking CNS depressants.(8) If concurrent use is necessary, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect. If starting a gabapentinoid with an opioid analgesic, prescribe a lower initial dose of the gabapentinoid than indicated in the absence of an opioid and titrate based upon clinical response. If an opioid analgesic is indicated in a patient already taking a gabapentinoid, prescribe a lower dose of the opioid and titrate based upon clinical response.(1) Respiratory depression can occur at any time during opioid therapy, especially during therapy initiation and following dosage increases. Consider this risk when using concurrently with other agents that may cause CNS depression.(9) Monitor patients receiving concurrent therapy for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.(1) DISCUSSION: In a study in 12 healthy males, administration of a single dose of morphine (60 mg sustained release) increased the area-under-curve (AUC) of a single dose of gabapentin (600 mg) by 44%.(1,3,4) There were no affects on the pharmacokinetics of morphine.(1,3,4) The combination of gabapentin plus morphine increased pain tolerance over the combination of morphine plus placebo. Side effects were not significantly different between morphine plus placebo and morphine plus gabapentin.(1) A retrospective, case-control study of opioid users in Ontario, Canada between August 1, 1997 and December 31, 2013 who died of an opioid-related cause matched cases to up to 4 controls who also used opioids. Use of gabapentin in the 120 days prior to death resulted in a significant increase in odds of opioid-related death (OR 1.99, CI=1.61-2.47, p<0.001), compared to opioid use alone. Use of moderate dose (900 mg to 1,799 mg daily) or high dose (>= 1,800 mg daily) gabapentin increased the odds of opioid-related death 60% compared to opioid use without gabapentin. Review of gabapentin prescriptions from calendar year 2013 found that 46% of gabapentin users received at least 1 opioid prescription.(3) Among 49 case reports submitted to FDA over a 5 year period (2012-2017), 12 people died from respiratory depression with gabapentinoids. Two randomized, double-blind, placebo-controlled clinical trials in healthy people, three observational studies, and several studies in animals were reviewed. A trial showed that using pregabalin alone and using it with an opioid pain reliever can depress breathing function. Three observational studies showed a relationship between gabapentinoids given before surgery and respiratory depression occurring after surgery. Several animal studies also showed that pregabalin plus opioids can depress respiratory function.(7) A retrospective cohort study evaluated the risk of mortality among Medicare beneficiaries aged 65 and older who were taking gabapentin with or without concurrent use of opioids. All-cause mortality in gabapentin users compared to duloxetine users was 12.16 per 1,000 person years vs. 9.94 per 1,000 person years, respectively. Adjusted for covariates, the risk of all-cause mortality among gabapentin users on high-dose opioids was more than double the control group (hazard ratio (HR) 2.03, CI=1.19-3.46).(10)	HYCODAN, HYDROCODONE-CHLORPHENIRAMNE ER, HYDROCODONE-HOMATROPINE MBR, HYDROMET, PROMETHAZINE-CODEINE, TUXARIN ER
Sodium Iodide I 131/Myelosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1) DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)	HICON, SODIUM IODIDE I-131

There are 3 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Pregabalin/Thiazolidinedione Antidiabetics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Both pregabalin and thiazolidinedione antidiabetics may cause weight gain and/or fluid retention.(1) CLINICAL EFFECTS: Concurrent use of pregabalin and thiazolidinedione antidiabetics may result in weight gain and/or fluid retention, which may increase the risk of heart failure in patients with preexisting cardiac conditions.(1) PREDISPOSING FACTORS: Preexisting cardiac conditions may increase the risk of heart failure.(1) PATIENT MANAGEMENT: Patients should be monitored for weight gain and/or fluid retention when taking pregabalin with the thiazolidinedione antidiabetics agents together. Congestive heart failure or worsening of existing congestive heart failure may occur. DISCUSSION: In clinical trials, the incidence of peripheral edema was 3% of patients receiving a thiazolidinedione antidiabetic alone, 8% of patients receiving pregabalin alone, and 19% of patients on combination therapy. The incidence of weight gain was 0% of patients receiving a thiazolidinedione antidiabetic alone, 4% of patients receiving pregabalin alone, and 7.5% of patients on combination therapy.(1)	ACTOPLUS MET, ACTOS, ALOGLIPTIN-PIOGLITAZONE, DUETACT, OSENI, PIOGLITAZONE HCL, PIOGLITAZONE-GLIMEPIRIDE, PIOGLITAZONE-METFORMIN
Gabapentinoids/Opioids (IR & ER) SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Opioid-induced reduction in GI motility may increase the absorption of gabapentin and pregabalin.(1) Gabapentin and pregabalin may reverse opioid-induced tolerance of respiratory depression.(2) Concurrent use may result in profound sedation, respiratory depression, coma, and/or death.(3) CLINICAL EFFECTS: Concurrent use of opioids may result in elevated levels of and toxicity from gabapentin and pregabalin, including profound sedation, respiratory depression, coma, and/or death.(1-7) PREDISPOSING FACTORS: Patients who are elderly, are taking other CNS depressants, have decreased renal function, and/or have conditions that reduce lung function (e.g. Chronic Obstructive Pulmonary Disease [COPD]) may be at a higher risk of this interaction. PATIENT MANAGEMENT: Limit prescribing opioid analgesics and gabapentinoids to patients for whom alternatives are inadequate.(1) If concurrent use is necessary, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect. If starting a gabapentinoid with an opioid analgesic, prescribe a lower initial dose of the gabapentinoid than indicated in the absence of an opioid and titrate based upon clinical response. If an opioid analgesic is indicated in a patient already taking a gabapentinoid, prescribe a lower dose of the opioid and titrate based upon clinical response.(1) Respiratory depression can occur at any time during opioid therapy, especially during therapy initiation and following dosage increases. Consider this risk when using concurrently with other agents that may cause CNS depression.(8) Monitor patients receiving concurrent therapy for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.(1) Discuss naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing naloxone to patients prescribed medicines to treat OUD or opioid analgesics (such as those taking CNS depressants) who are at increased risk of opioid overdose and when a patient has household members/close contacts at risk for accidental overdose.(9) DISCUSSION: In a study in 12 healthy males, administration of a single dose of morphine (60 mg sustained release) increased the area-under-curve (AUC) of a single dose of gabapentin (600 mg) by 44%.(1,3,4) There were no affects on the pharmacokinetics of morphine.(1,3,4) The combination of gabapentin plus morphine increased pain tolerance over the combination of morphine plus placebo. Side effects were not significantly different between morphine plus placebo and morphine plus gabapentin.(1) A retrospective, case-control study of opioid users in Ontario, Canada between August 1, 1997 and December 31, 2013 who died of an opioid-related cause matched cases to up to 4 controls who also used opioids. Use of gabapentin in the 120 days prior to death resulted in a significant increase in odds of opioid-related death (OR 1.99, CI=1.61-2.47, p<0.001), compared to opioid use alone. Use of moderate dose (900 mg to 1,799 mg daily) or high dose (>= 1,800 mg daily) gabapentin increased the odds of opioid-related death 60% compared to opioid use without gabapentin. Review of gabapentin prescriptions from calendar year 2013 found that 46% of gabapentin users received at least 1 opioid prescription.(3) Among 49 case reports submitted to FDA over a 5 year period (2012-2017), 12 people died from respiratory depression with gabapentinoids. Two randomized, double-blind, placebo-controlled clinical trials in healthy people, three observational studies, and several studies in animals were reviewed. A trial showed that using pregabalin alone and using it with an opioid pain reliever can depress breathing function. Three observational studies showed a relationship between gabapentinoids given before surgery and respiratory depression occurring after surgery. Several animal studies also showed that pregabalin plus opioids can depress respiratory function.(7) A retrospective cohort study evaluated the risk of mortality among Medicare beneficiaries aged 65 and older who were taking gabapentin with or without concurrent use of opioids. All-cause mortality in gabapentin users compared to duloxetine users was 12.16 per 1,000 person years vs. 9.94 per 1,000 person years, respectively. Adjusted for covariates, the risk of all-cause mortality among gabapentin users on high-dose opioids was more than double the control group (hazard ratio (HR) 2.03, CI=1.19-3.46).(10)	ACETAMIN-CAFF-DIHYDROCODEINE, ACETAMINOPHEN-CODEINE, APADAZ, ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, BELBUCA, BELLADONNA-OPIUM, BENZHYDROCODONE-ACETAMINOPHEN, BRIXADI, BUPRENORPHINE, BUPRENORPHINE HCL, BUPRENORPHINE-NALOXONE, BUTALB-ACETAMINOPH-CAFF-CODEIN, BUTORPHANOL TARTRATE, BUTRANS, CARISOPRODOL-ASPIRIN-CODEINE, CODEINE PHOSPHATE, CODEINE SULFATE, CONZIP, DEMEROL, DIHYDROCODEINE BITARTRATE, DILAUDID, DIPHENOXYLATE-ATROPINE, DISKETS, DSUVIA, DURAMORPH, ENDOCET, FENTANYL, FENTANYL CITRATE, FENTANYL CITRATE-0.9% NACL, FENTANYL CITRATE-D5W, FENTANYL CITRATE-STERILE WATER, FENTANYL CITRATE-WATER, FENTANYL-BUPIVACAINE-0.9% NACL, FENTANYL-BUPIVACAINE-NACL, FENTANYL-ROPIVACAINE-0.9% NACL, FENTANYL-ROPIVACAINE-NACL, FIORICET WITH CODEINE, HYDROCODONE BITARTRATE, HYDROCODONE BITARTRATE ER, HYDROCODONE-ACETAMINOPHEN, HYDROCODONE-IBUPROFEN, HYDROMORPHONE ER, HYDROMORPHONE HCL, HYDROMORPHONE HCL-0.9% NACL, HYDROMORPHONE HCL-D5W, HYDROMORPHONE HCL-NACL, HYDROMORPHONE HCL-WATER, HYSINGLA ER, INFUMORPH, LEVORPHANOL TARTRATE, LOMOTIL, MEPERIDINE HCL, MEPERIDINE HCL-0.9% NACL, METHADONE HCL, METHADONE HCL-0.9% NACL, METHADONE HCL-NACL, METHADONE INTENSOL, METHADOSE, MITIGO, MORPHINE SULFATE, MORPHINE SULFATE ER, MORPHINE SULFATE-0.9% NACL, MORPHINE SULFATE-NACL, MOTOFEN, MS CONTIN, NALBUPHINE HCL, NALOCET, NUCYNTA, NUCYNTA ER, OLINVYK, OPIUM TINCTURE, OXYCODONE HCL, OXYCODONE HCL ER, OXYCODONE HYDROCHLORIDE, OXYCODONE-ACETAMINOPHEN, OXYCONTIN, OXYMORPHONE HCL, OXYMORPHONE HCL ER, PENTAZOCINE-NALOXONE HCL, PERCOCET, PRIMLEV, PROLATE, QDOLO, REMIFENTANIL HCL, ROXICODONE, ROXYBOND, SUBLOCADE, SUBOXONE, SUFENTANIL CITRATE, TRAMADOL HCL, TRAMADOL HCL ER, TRAMADOL HCL-ACETAMINOPHEN, TREZIX, ULTIVA, XTAMPZA ER, ZUBSOLV
Gabapentinoids/Benzodiazepines SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concurrent use may result in profound sedation, respiratory depression, coma, and/or death.(1-3) CLINICAL EFFECTS: Concurrent use of benzodiazepines may result in elevated levels of and toxicity from gabapentin and pregabalin, including profound sedation, respiratory depression, coma, and/or death.(1-3) PREDISPOSING FACTORS: Patients who are elderly, are taking other CNS depressants, have decreased renal function, and/or have conditions that reduce lung function (e.g. Chronic Obstructive Pulmonary Disease [COPD]) may be at a higher risk of this interaction. PATIENT MANAGEMENT: Limit prescribing benzodiazepines and gabapentinoids to patients for whom alternatives are inadequate.(1) If concurrent use is necessary, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect. If starting a gabapentinoid with an benzodiazepine, prescribe a lower initial dose of the gabapentinoid than indicated in the absence of an opioid and titrate based upon clinical response. If a benzodiazepine is indicated (other than an indication of epilepsy) in a patient already taking a gabapentinoid, prescribe a lower dose of the benzodiazepine and titrate based upon clinical response.(1) Monitor patients receiving concurrent therapy for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.(1) DISCUSSION: Clinical trials have shown no pharmacokinetic interaction between pregabalin (300 mg BID) and lorazepam (1 mg single dose).(2) Among 49 case reports submitted to FDA over a 5 year period (2012-2017), 12 people died from respiratory depression with gabapentinoids. Two randomized, double-blind, placebo-controlled clinical trials in healthy people, three observational studies, and several studies in animals were reviewed. A trial showed that using pregabalin alone and using it with an opioid pain reliever can depress breathing function. Three observational studies showed a relationship between gabapentinoids given before surgery and respiratory depression occurring after surgery. Several animal studies also showed that pregabalin plus opioids can depress respiratory function. Benzodiazepines are expected to have a similar effect when used with gabapentinoids.(1)	ALPRAZOLAM, ALPRAZOLAM ER, ALPRAZOLAM INTENSOL, ALPRAZOLAM ODT, ALPRAZOLAM XR, ATIVAN, BYFAVO, CHLORDIAZEPOXIDE HCL, CHLORDIAZEPOXIDE-AMITRIPTYLINE, CHLORDIAZEPOXIDE-CLIDINIUM, CLOBAZAM, CLONAZEPAM, CLORAZEPATE DIPOTASSIUM, DIAZEPAM, DORAL, ESTAZOLAM, FLURAZEPAM HCL, HALCION, KLONOPIN, LIBRAX, LORAZEPAM, LORAZEPAM INTENSOL, LOREEV XR, MIDAZOLAM, MIDAZOLAM HCL, MIDAZOLAM HCL-0.8% NACL, MIDAZOLAM HCL-0.9% NACL, MIDAZOLAM HCL-D5W, MIDAZOLAM HCL-NACL, MIDAZOLAM-0.9% NACL, MIDAZOLAM-NACL, MKO (MIDAZOLAM-KETAMINE-ONDAN), NAYZILAM, ONFI, OXAZEPAM, QUAZEPAM, RESTORIL, SYMPAZAN, TEMAZEPAM, TRIAZOLAM, VALIUM, VALTOCO, XANAX, XANAX XR

The following contraindication information is available for PREGABALIN (pregabalin):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

Known hypersensitivity to pregabalin or any ingredient in the formulation.

There are 0 contraindications.

There are 10 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Acute decompensated heart failure
Angioedema
Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Chronic obstructive pulmonary disease
Myopathy with CK elevation
Respiratory depression
Suicidal ideation

There are 8 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Atrioventricular block
Chronic heart failure
Depression
Drug abuse
Kidney disease with likely reduction in glomerular filtration rate (GFr)
Peripheral edema
Reduced visual acuity
Weight gain

The following adverse reaction information is available for PREGABALIN (pregabalin):

Overview
Severe
Less Severe

Adverse reaction overview.

The most common adverse effects in adults receiving conventional pregabalin preparations across indications in clinical trials (occurring in 5% or more of patients and more frequently than placebo) include dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, and abnormal thinking (primarily difficulty with concentration/attention). The most common adverse effects in pediatric patients receiving conventional pregabalin for the treatment of partial seizures (occurring in 5% or more of patients and more frequently than placebo) include somnolence, weight gain, and increased appetite. The most common adverse effects in adults receiving extended-release pregabalin in clinical studies include dizziness, somnolence, headache, fatigue, peripheral edema, nausea, blurred vision, dry mouth, and weight gain.

Other adverse effects commonly reported in adults receiving conventional pregabalin in combination with other anticonvulsant agents in the management of partial seizures include ataxia, tremor, amnesia, speech disorder, increased appetite, peripheral edema, diplopia, and accidental injury. Other adverse effects commonly reported in adults receiving conventional pregabalin for the management of PHN include headache, ataxia, constipation, peripheral edema, infection, and pain. Other adverse effects commonly reported in adults receiving conventional pregabalin for the management of DPN include asthenia and peripheral edema.

Other adverse effects commonly reported in adults receiving conventional pregabalin for the management of fibromyalgia include headache, euphoric mood, attention disturbance, balance disorder, constipation, fatigue, peripheral edema, increased appetite, and sinusitis. Other adverse effects commonly reported in adults receiving conventional pregabalin for the management of neuropathic pain associated with spinal cord injury include fatigue, peripheral edema, constipation, nasopharyngitis, and muscle weakness.

There are 24 severe adverse reactions.

More Frequent	Less Frequent
Ataxia	Facial edema Hypoglycemic disorder Infection Thrombocytopenic disorder

Rare/Very Rare
Accidental fall Angioedema Behavioral disorders Blistering skin Bullous pemphigoid Diplopia Drug dependence Dysarthria Dyskinesia Heart failure Kidney stone Prolonged PR interval Pulmonary edema Respiratory depression Suicidal Suicidal ideation Tinnitus Urticaria Wheezing

There are 69 less severe adverse reactions.

More Frequent	Less Frequent
Blurred vision Concentration difficulty Disturbance in thinking Dizziness Drowsy Fatigue Peripheral edema Weight gain Xerostomia	Accidental injury Acute abdominal pain Acute cognitive impairment Arthralgia Back pain Constipation Erectile dysfunction Euphoria Gait abnormality Gastroenteritis General weakness Headache disorder Hypoesthesia Increased appetite Memory impairment Muscle fasciculation Muscle spasm Nausea Orgasm disorder Pruritus of skin Sinusitis Vertigo

Rare/Very Rare
Abdominal distension Acute bacterial otitis media Amenorrhea Bronchitis Chest pain Conjunctivitis Cramps in legs Depersonalization Diarrhea Dysmenorrhea Dyspareunia Dyspnea Dysuria Ecchymosis Edema Erythema Fever Flatulence Flu-like symptoms Gynecomastia Hematuria Hyperhidrosis Hypertonia Increased urinary frequency Libido changes Muscle weakness Myalgia Nail disorders Nervousness Nystagmus Skin rash Stupor Symptoms of anxiety Tremor Urinary incontinence Urinary retention Visual changes Vomiting

Rare/Very Rare

Abdominal distension
Acute bacterial otitis media
Amenorrhea
Bronchitis
Chest pain
Conjunctivitis
Cramps in legs
Depersonalization
Diarrhea
Dysmenorrhea
Dyspareunia
Dyspnea
Dysuria
Ecchymosis
Edema
Erythema
Fever
Flatulence
Flu-like symptoms
Gynecomastia
Hematuria
Hyperhidrosis
Hypertonia
Increased urinary frequency
Libido changes
Muscle weakness
Myalgia
Nail disorders
Nervousness
Nystagmus
Skin rash
Stupor
Symptoms of anxiety
Tremor
Urinary incontinence
Urinary retention
Visual changes
Vomiting

The following precautions are available for PREGABALIN (pregabalin):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy of pregabalin conventional preparations for adjunctive treatment of partial seizures have not been established in children younger than 1 month of age. Use of conventional pregabalin in older children is supported by evidence from 2 randomized placebo-controlled studies. (See Uses: Seizure Disorders.) Although the youngest patient evaluated in these studies was 3 months of age, use of pregabalin in infants 1-3 months of age can be supported by additional pharmacokinetic data.

Clearance of pregabalin (normalized for body weight) is approximately 40% higher in patients weighing less than 30 kg. For children weighing less than 30 kg, a dosage increase is required to achieve comparable exposure to those weighing 30 kg or more. Safety and efficacy of pregabalin for the treatment of fibromyalgia, diabetic peripheral neuropathy (DPN), postherpetic neuralgia (PHN), or neuropathic pain associated with spinal cord injury have not been established in pediatric patients. Safety and efficacy of pregabalin extended-release tablets have not been established in pediatric patients.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Women who are pregnant while receiving pregabalin should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry at 888-233-2334 (for patients); registry information also is available on the website https://www.aedpregnancyregistry.org/.

There are no adequate and well-controlled studies of pregabalin in pregnant women; however, based on animal studies, pregabalin may cause fetal harm. In animal reproductive studies, pregabalin produced developmental toxicity (e.g., fetal structural abnormalities, skeletal malformations, retarded ossification, decreased fetal body weight) when administered orally to pregnant animals during the period of organogenesis at exposure levels 16 times higher than those associated with the maximum recommended human dosage of 600 mg daily. When pregabalin was administered to female rats throughout the period of gestation and lactation, growth retardation, impairment to the nervous and reproductive systems, and decreased survival were observed in the offspring.

Pregabalin is distributed into human milk at steady-state concentrations approximately 76% of those in maternal plasma. Following administration of maternal dosages of 300 mg daily, the estimated average infant dose of pregabalin from breast milk is 0.31 mg/kg daily (approximately 7% of the maternal dose). Because of the potential for tumorigenicity (see Carcinogenicity under Cautions: Warnings/Precautions), breastfeeding is not recommended during pregabalin therapy.

The manufacturer states that no substantial differences in safety and efficacy have been observed in geriatric patients relative to younger adults; however, increased sensitivity to pregabalin in certain individuals cannot be ruled out. In controlled clinical studies of patients with fibromyalgia, neurological adverse reactions including dizziness, blurred vision, balance disorder, tremor, confusional state, abnormal coordination, and lethargy occurred more frequently in patients 65 years of age and older than in younger adults. In addition, FDA warns that geriatric patients receiving gabapentinoids are at increased risk of potentially serious, life-threatening, or fatal respiratory depression; pregabalin therapy should be initiated at the lowest dosage and titrated carefully with close monitoring in such patients.

It should be considered that pregabalin is substantially excreted by the kidneys, and the risk of adverse reactions to the drug may be increased in patients with impaired renal function. The dosage should be adjusted for geriatric patients with renal impairment. Monitoring renal function in geriatric patients may be helpful. (See Dosage and Administration: Special Populations.)

The following icd codes are available for PREGABALIN (pregabalin)'s list of indications:

Diabetic peripheral neuropathy
E08.40	Diabetes mellitus due to underlying condition with diabetic neuropathy, unspecified
E08.42	Diabetes mellitus due to underlying condition with diabetic polyneuropathy
E09.40	Drug or chemical induced diabetes mellitus with neurological complications with diabetic neuropathy, unspecified
E09.42	Drug or chemical induced diabetes mellitus with neurological complications with diabetic polyneuropathy
E10.40	Type 1 diabetes mellitus with diabetic neuropathy, unspecified
E10.42	Type 1 diabetes mellitus with diabetic polyneuropathy
E11.40	Type 2 diabetes mellitus with diabetic neuropathy, unspecified
E11.42	Type 2 diabetes mellitus with diabetic polyneuropathy
E13.40	Other specified diabetes mellitus with diabetic neuropathy, unspecified
E13.42	Other specified diabetes mellitus with diabetic polyneuropathy
Fibromyalgia
M79.7	Fibromyalgia
Neuropathic pain associated with spinal cord injury
G59	Mononeuropathy in diseases classified elsewhere
G63	Polyneuropathy in diseases classified elsewhere
Partial epilepsy treatment adjunct
G40.0	Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset
G40.00	Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, not intractable
G40.009	Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, not intractable, without status epilepticus
G40.01	Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, intractable
G40.019	Localization-related (focal) (partial) idiopathic epilepsy and epileptic syndromes with seizures of localized onset, intractable, without status epilepticus
G40.1	Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures
G40.10	Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, not intractable
G40.109	Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, not intractable, without status epilepticus
G40.11	Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, intractable
G40.119	Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures, intractable, without status epilepticus
G40.2	Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures
G40.20	Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, not intractable
G40.209	Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, not intractable, without status epilepticus
G40.21	Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, intractable
G40.219	Localization-related (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures, intractable, without status epilepticus
Postherpetic neuralgia
B02.22	Postherpetic trigeminal neuralgia
B02.23	Postherpetic polyneuropathy