6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In all controlled and uncontrolled trials across various patient populations during the premarketing development of pregabalin, more than 10,000 patients have received pregabalin. Approximately 5,000 patients were treated for 6 months or more, over 3,100 patients were treated for 1 year or longer, and over 1,400 patients were treated for at least 2 years.
Adverse Reactions Most Commonly Leading to Discontinuation in All Premarketing Controlled Clinical Studies
In premarketing controlled trials of all adult populations combined, 14% of patients treated with pregabalin and 7% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin treatment group, the adverse reactions most frequently leading to discontinuation were dizziness (4%) and somnolence (4%). In the placebo group, 1% of patients withdrew due to dizziness and less than 1% withdrew due to somnolence. Other adverse reactions that led to discontinuation from controlled trials more frequently in the pregabalin group compared to the placebo group were ataxia, confusion, asthenia, thinking abnormal, blurred vision, incoordination, and peripheral edema (1% each).
Most Common Adverse Reactions in All Controlled Clinical Studies in Adults
In premarketing controlled trials of all adult patient populations combined (including DPN, PHN, and adult patients with partial-onset seizures), dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, and "thinking abnormal" (primarily difficulty with concentration/attention) were more commonly reported by subjects treated with pregabalin than by subjects treated with placebo (greater than or equal to 5% and twice the rate of that seen in placebo).
Controlled Studies with Neuropathic Pain Associated with Diabetic Peripheral Neuropathy
Adverse Reactions Leading to Discontinuation
In clinical trials in adults with neuropathic pain associated with diabetic peripheral neuropathy, 9% of patients treated with pregabalin and 4% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin treatment group, the most common reasons for discontinuation due to adverse reactions were dizziness (3%) and somnolence (2%). In comparison, less than 1% of placebo patients withdrew due to dizziness and somnolence. Other reasons for discontinuation from the trials, occurring with greater frequency in the pregabalin group than in the placebo group, were asthenia, confusion, and peripheral edema. Each of these events led to withdrawal in approximately 1% of patients.
Most Common Adverse Reactions
Table 4 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 1% of patients with neuropathic pain associated with diabetic neuropathy in the combined pregabalin group for which the incidence was greater in this combined pregabalin group than in the placebo group. A majority of pregabalin-treated patients in clinical studies had adverse reactions with a maximum intensity of “mild” or “moderate”.
| Body system Preferred term | 75 mg/day [N=77] % | 150 mg/day [N=212] % | 300 mg/day [N=321] % | 600 mg/day [N=369] % | All PGB * | Placebo |
|---|---|---|---|---|---|---|
| [N=979] % | [N=459] % | |||||
| ||||||
| Body as a whole | ||||||
| Asthenia | 4 | 2 | 4 | 7 | 5 | 2 |
| Accidental injury | 5 | 2 | 2 | 6 | 4 | 3 |
| Back pain | 0 | 2 | 1 | 2 | 2 | 0 |
| Chest pain | 4 | 1 | 1 | 2 | 2 | 1 |
| Face edema | 0 | 1 | 1 | 2 | 1 | 0 |
| Digestive system | ||||||
| Dry mouth | 3 | 2 | 5 | 7 | 5 | 1 |
| Constipation | 0 | 2 | 4 | 6 | 4 | 2 |
| Flatulence | 3 | 0 | 2 | 3 | 2 | 1 |
| Metabolic and nutritional disorders | ||||||
| Peripheral edema | 4 | 6 | 9 | 12 | 9 | 2 |
| Weight gain | 0 | 4 | 4 | 6 | 4 | 0 |
| Edema | 0 | 2 | 4 | 2 | 2 | 0 |
| Hypoglycemia | 1 | 3 | 2 | 1 | 2 | 1 |
| Nervous system | ||||||
| Dizziness | 8 | 9 | 23 | 29 | 21 | 5 |
| Somnolence | 4 | 6 | 13 | 16 | 12 | 3 |
| Neuropathy | 9 | 2 | 2 | 5 | 4 | 3 |
| Ataxia | 6 | 1 | 2 | 4 | 3 | 1 |
| Vertigo | 1 | 2 | 2 | 4 | 3 | 1 |
| Confusion | 0 | 1 | 2 | 3 | 2 | 1 |
| Euphoria | 0 | 0 | 3 | 2 | 2 | 0 |
| Incoordination | 1 | 0 | 2 | 2 | 2 | 0 |
| Thinking abnormal † | 1 | 0 | 1 | 3 | 2 | 0 |
| Tremor | 1 | 1 | 1 | 2 | 1 | 0 |
| Abnormal gait | 1 | 0 | 1 | 3 | 1 | 0 |
| Amnesia | 3 | 1 | 0 | 2 | 1 | 0 |
| Nervousness | 0 | 1 | 1 | 1 | 1 | 0 |
| Respiratory system | ||||||
| Dyspnea | 3 | 0 | 2 | 2 | 2 | 1 |
| Special senses | ||||||
| Blurry vision ‡ | 3 | 1 | 3 | 6 | 4 | 2 |
| Abnormal vision | 1 | 0 | 1 | 1 | 1 | 0 |
Controlled Studies in Postherpetic Neuralgia
Adverse Reactions Leading to Discontinuation
In clinical trials in adults with postherpetic neuralgia, 14% of patients treated with pregabalin and 7% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin treatment group, the most common reasons for discontinuation due to adverse reactions were dizziness (4%) and somnolence (3%). In comparison, less than 1% of placebo patients withdrew due to dizziness and somnolence. Other reasons for discontinuation from the trials, occurring in greater frequency in the pregabalin group than in the placebo group, were confusion (2%), as well as peripheral edema, asthenia, ataxia, and abnormal gait (1% each).
Most Common Adverse Reactions
Table 5 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 1% of patients with neuropathic pain associated with postherpetic neuralgia in the combined pregabalin group for which the incidence was greater in this combined pregabalin group than in the placebo group. In addition, an event is included, even if the incidence in the all pregabalin group is not greater than in the placebo group, if the incidence of the event in the 600 mg/day group is more than twice that in the placebo group. A majority of pregabalin-treated patients in clinical studies had adverse reactions with a maximum intensity of “mild” or “moderate”. Overall, 12.4% of all pregabalin-treated patients and 9.0% of all placebo-treated patients had at least one severe event while 8% of pregabalin-treated patients and 4.3% of placebo-treated patients had at least one severe treatment-related adverse event.
| Body system Preferred term | 75 mg/d [N=84] % | 150 mg/d [N=302] % | 300 mg/d [N=312] % | 600 mg/d [N=154] % | All PGB * [N=852] % | Placebo [N=398] % |
|---|---|---|---|---|---|---|
| ||||||
| Body as a whole | ||||||
| Infection | 14 | 8 | 6 | 3 | 7 | 4 |
| Headache | 5 | 9 | 5 | 8 | 7 | 5 |
| Pain | 5 | 4 | 5 | 5 | 5 | 4 |
| Accidental injury | 4 | 3 | 3 | 5 | 3 | 2 |
| Flu syndrome | 1 | 2 | 2 | 1 | 2 | 1 |
| Face edema | 0 | 2 | 1 | 3 | 2 | 1 |
| Digestive system | ||||||
| Dry mouth | 7 | 7 | 6 | 15 | 8 | 3 |
| Constipation | 4 | 5 | 5 | 5 | 5 | 2 |
| Flatulence | 2 | 1 | 2 | 3 | 2 | 1 |
| Vomiting | 1 | 1 | 3 | 3 | 2 | 1 |
| Metabolic and nutritional disorders | ||||||
| Peripheral edema | 0 | 8 | 16 | 16 | 12 | 4 |
| Weight gain | 1 | 2 | 5 | 7 | 4 | 0 |
| Edema | 0 | 1 | 2 | 6 | 2 | 1 |
| Musculoskeletal system | ||||||
| Myasthenia | 1 | 1 | 1 | 1 | 1 | 0 |
| Nervous system | ||||||
| Dizziness | 11 | 18 | 31 | 37 | 26 | 9 |
| Somnolence | 8 | 12 | 18 | 25 | 16 | 5 |
| Ataxia | 1 | 2 | 5 | 9 | 5 | 1 |
| Abnormal gait | 0 | 2 | 4 | 8 | 4 | 1 |
| Confusion | 1 | 2 | 3 | 7 | 3 | 0 |
| Thinking abnormal † | 0 | 2 | 1 | 6 | 2 | 2 |
| Incoordination | 2 | 2 | 1 | 3 | 2 | 0 |
| Amnesia | 0 | 1 | 1 | 4 | 2 | 0 |
| Speech disorder | 0 | 0 | 1 | 3 | 1 | 0 |
| Respiratory system | ||||||
| Bronchitis | 0 | 1 | 1 | 3 | 1 | 1 |
| Special senses | ||||||
| Blurry vision ‡ | 1 | 5 | 5 | 9 | 5 | 3 |
| Diplopia | 0 | 2 | 2 | 4 | 2 | 0 |
| Abnormal vision | 0 | 1 | 2 | 5 | 2 | 0 |
| Eye Disorder | 0 | 1 | 1 | 2 | 1 | 0 |
| Urogenital System | ||||||
| Urinary Incontinence | 0 | 1 | 1 | 2 | 1 | 0 |
Controlled Studies of Adjunctive Therapy for Partial-Onset Seizures in Adult Patients
Adverse Reactions Leading to Discontinuation
Approximately 15% of patients receiving pregabalin and 6% of patients receiving placebo in trials of adjunctive therapy for partial-onset seizures discontinued prematurely due to adverse reactions. In the pregabalin treatment group, the adverse reactions most frequently leading to discontinuation were dizziness (6%), ataxia (4%), and somnolence (3%). In comparison, less than 1% of patients in the placebo group withdrew due to each of these events. Other adverse reactions that led to discontinuation of at least 1% of patients in the pregabalin group and at least twice as frequently compared to the placebo group were asthenia, diplopia, blurred vision, thinking abnormal, nausea, tremor, vertigo, headache, and confusion (which each led to withdrawal in 2% or less of patients).
Most Common Adverse Reactions
Table 6 lists all dose-related adverse reactions occurring in at least 2% of all pregabalin-treated patients. Dose-relatedness was defined as the incidence of the adverse event in the 600 mg/day group was at least 2% greater than the rate in both the placebo and 150 mg/day groups. In these studies, 758 patients received pregabalin and 294 patients received placebo for up to 12 weeks. A majority of pregabalin-treated patients in clinical studies had adverse reactions with a maximum intensity of “mild” or “moderate”.
| 150 mg/d | 300 mg/d | 600 mg/d | All PGB * | Placebo | |
|---|---|---|---|---|---|
| Body System Preferred Term | [N = 185] | [N = 90] | [N = 395] | [N = 670] † | [N = 294] |
| % | % | % | % | % | |
| |||||
| Body as a Whole | |||||
| Accidental Injury | 7 | 11 | 10 | 9 | 5 |
| Pain | 3 | 2 | 5 | 4 | 3 |
| Digestive System | |||||
| Increased Appetite | 2 | 3 | 6 | 5 | 1 |
| Dry Mouth | 1 | 2 | 6 | 4 | 1 |
| Constipation | 1 | 1 | 7 | 4 | 2 |
| Metabolic and Nutritional Disorders | |||||
| Weight Gain | 5 | 7 | 16 | 12 | 1 |
| Peripheral Edema | 3 | 3 | 6 | 5 | 2 |
| Nervous System | |||||
| Dizziness | 18 | 31 | 38 | 32 | 11 |
| Somnolence | 11 | 18 | 28 | 22 | 11 |
| Ataxia | 6 | 10 | 20 | 15 | 4 |
| Tremor | 3 | 7 | 11 | 8 | 4 |
| Thinking Abnormal ‡ | 4 | 8 | 9 | 8 | 2 |
| Amnesia | 3 | 2 | 6 | 5 | 2 |
| Speech Disorder | 1 | 2 | 7 | 5 | 1 |
| Incoordination | 1 | 3 | 6 | 4 | 1 |
| Abnormal Gait | 1 | 3 | 5 | 4 | 0 |
| Twitching | 0 | 4 | 5 | 4 | 1 |
| Confusion | 1 | 2 | 5 | 4 | 2 |
| Myoclonus | 1 | 0 | 4 | 2 | 0 |
| Special Senses | |||||
| Blurred Vision § | 5 | 8 | 12 | 10 | 4 |
| Diplopia | 5 | 7 | 12 | 9 | 4 |
| Abnormal Vision | 3 | 1 | 5 | 4 | 1 |
Controlled Study of Adjunctive Therapy for Partial-Onset Seizures in Patients 4 to Less Than 17 Years of Age
Adverse Reactions Leading to Discontinuation
Approximately 2.5% of patients receiving pregabalin and no patients receiving placebo in trials of adjunctive therapy for partial-onset seizures discontinued prematurely due to adverse reactions. In the pregabalin treatment group, the adverse reactions leading to discontinuation were somnolence (3 patients), worsening of epilepsy (1 patient), and hallucination (1 patient).
Most Common Adverse Reactions
Table 7 lists all dose-related adverse reactions occurring in at least 2% of all pregabalin -treated patients. Dose-relatedness was defined as an incidence of the adverse event in the 10 mg/kg/day group that was at least 2% greater than the rate in both the placebo and 2.5 mg/kg/day groups. In this study, 201 patients received pregabalin and 94 patients received placebo for up to 12 weeks. A majority of pregabalin-treated patients in the clinical study had adverse reactions with a maximum intensity of "mild" or "moderate”.
| Body System Preferred Term | 2.5 mg/kg/day * [N=104] % | 10 mg/kg/day † [N=97] % | All PGB [N=201] % | Placebo [N=94] % |
|---|---|---|---|---|
| Abbreviations: N=number of patients; PGB = pregabalin. | ||||
| ||||
| Gastrointestinal disorders | ||||
| Salivary hypersecretion | 1 | 4 | 2 | 0 |
| Investigations | ||||
| Weight increased | 4 | 13 | 8 | 4 |
| Metabolism and nutrition disorders | ||||
| Increased appetite | 7 | 10 | 8 | 4 |
| Nervous system disorders | ||||
| Somnolence | 17 | 26 | 21 | 14 |
Controlled Study of Adjunctive Therapy for Partial-Onset Seizures in Patients 1 Month to Less Than 4 Years of Age
Most Common Adverse Reactions
Table 8 lists all dose-related adverse reactions occurring in at least 2% of all pregabalin-treated patients. Dose-relatedness was defined as an incidence of the adverse event in the 14 mg/kg/day group that was at least 2% greater than the rate in both the placebo and 7 mg/kg/day groups. In this study, 105 patients received pregabalin and 70 patients received placebo for up to 14 days.
| Body System Preferred Term | 7 mg/kg/day [N=71] % | 14 mg/kg/day [N=34] % | All PGB [N=105] % | Placebo [N=70] % |
|---|---|---|---|---|
| Abbreviations: N=number of patients; PGB=pregabalin. | ||||
| ||||
| Nervous system disorders | ||||
| Somnolence * | 13 | 21 | 15 | 9 |
| Infections and infestations | ||||
| Pneumonia | 1 | 9 | 4 | 0 |
| Viral infection | 3 | 6 | 4 | 3 |
Controlled Studies with Fibromyalgia
Adverse Reactions Leading to Discontinuation
In clinical trials of patients with fibromyalgia, 19% of patients treated with pregabalin (150 mg/day to 600 mg/day) and 10% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin treatment group, the most common reasons for discontinuation due to adverse reactions were dizziness (6%) and somnolence (3%). In comparison, less than 1% of placebo-treated patients withdrew due to dizziness and somnolence.
Other reasons for discontinuation from the trials, occurring with greater frequency in the pregabalin treatment group than in the placebo treatment group, were fatigue, headache, balance disorder, and weight increased. Each of these adverse reactions led to withdrawal in approximately 1% of patients.
Most Common Adverse Reactions
Table 9 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 2% of patients with fibromyalgia in the ‘all pregabalin’ treatment group for which the incidence was greater than in the placebo treatment group. A majority of pregabalin-treated patients in clinical studies experienced adverse reactions with a maximum intensity of "mild" or "moderate".
| System Organ Class Preferred term | 150 mg/d [N=132] % | 300 mg/d [N=502] % | 450 mg/d [N=505] % | 600 mg/d [N=378] % | All PGB * | Placebo |
|---|---|---|---|---|---|---|
| [N=1,517] % | [N=505] % | |||||
| ||||||
| Ear and Labyrinth Disorders | ||||||
| Vertigo | 2 | 2 | 2 | 1 | 2 | 0 |
| Eye Disorders | ||||||
| Vision blurred | 8 | 7 | 7 | 12 | 8 | 1 |
| Gastrointestinal Disorders | ||||||
| Dry mouth | 7 | 6 | 9 | 9 | 8 | 2 |
| Constipation | 4 | 4 | 7 | 10 | 7 | 2 |
| Vomiting | 2 | 3 | 3 | 2 | 3 | 2 |
| Flatulence | 1 | 1 | 2 | 2 | 2 | 1 |
| Abdominal distension | 2 | 2 | 2 | 2 | 2 | 1 |
| General Disorders and Administrative Site Conditions | ||||||
| Fatigue | 5 | 7 | 6 | 8 | 7 | 4 |
| Edema peripheral | 5 | 5 | 6 | 9 | 6 | 2 |
| Chest pain | 2 | 1 | 1 | 2 | 2 | 1 |
| Feeling abnormal | 1 | 3 | 2 | 2 | 2 | 0 |
| Edema | 1 | 2 | 1 | 2 | 2 | 1 |
| Feeling drunk | 1 | 2 | 1 | 2 | 2 | 0 |
| Infections and Infestations | ||||||
| Sinusitis | 4 | 5 | 7 | 5 | 5 | 4 |
| Investigations | ||||||
| Weight increased | 8 | 10 | 10 | 14 | 11 | 2 |
| Metabolism and Nutrition Disorders | ||||||
| Increased appetite | 4 | 3 | 5 | 7 | 5 | 1 |
| Fluid retention | 2 | 3 | 3 | 2 | 2 | 1 |
| Musculoskeletal and Connective Tissue Disorders | ||||||
| Arthralgia | 4 | 3 | 3 | 6 | 4 | 2 |
| Muscle spasms | 2 | 4 | 4 | 4 | 4 | 2 |
| Back pain | 2 | 3 | 4 | 3 | 3 | 3 |
| Nervous System Disorders | ||||||
| Dizziness | 23 | 31 | 43 | 45 | 38 | 9 |
| Somnolence | 13 | 18 | 22 | 22 | 20 | 4 |
| Headache | 11 | 12 | 14 | 10 | 12 | 12 |
| Disturbance in attention | 4 | 4 | 6 | 6 | 5 | 1 |
| Balance disorder | 2 | 3 | 6 | 9 | 5 | 0 |
| Memory impairment | 1 | 3 | 4 | 4 | 3 | 0 |
| Coordination abnormal | 2 | 1 | 2 | 2 | 2 | 1 |
| Hypoesthesia | 2 | 2 | 3 | 2 | 2 | 1 |
| Lethargy | 2 | 2 | 1 | 2 | 2 | 0 |
| Tremor | 0 | 1 | 3 | 2 | 2 | 0 |
| Psychiatric Disorders | ||||||
| Euphoric Mood | 2 | 5 | 6 | 7 | 6 | 1 |
| Confusional state | 0 | 2 | 3 | 4 | 3 | 0 |
| Anxiety | 2 | 2 | 2 | 2 | 2 | 1 |
| Disorientation | 1 | 0 | 2 | 1 | 2 | 0 |
| Depression | 2 | 2 | 2 | 2 | 2 | 2 |
| Respiratory, Thoracic and Mediastinal Disorders | ||||||
| Pharyngolaryngeal pain | 2 | 1 | 3 | 3 | 2 | 2 |
Controlled Studies in Neuropathic Pain Associated with Spinal Cord Injury
Adverse Reactions Leading to Discontinuation
In clinical trials of adults with neuropathic pain associated with spinal cord injury, 13% of patients treated with pregabalin and 10% of patients treated with placebo discontinued prematurely due to adverse reactions. In the pregabalin treatment group, the most common reasons for discontinuation due to adverse reactions were somnolence (3%) and edema (2%). In comparison, none of the placebo-treated patients withdrew due to somnolence and edema. Other reasons for discontinuation from the trials, occurring with greater frequency in the pregabalin treatment group than in the placebo treatment group, were fatigue and balance disorder. Each of these adverse reactions led to withdrawal in less than 2% of patients.
Most Common Adverse Reactions
Table 10 lists all adverse reactions, regardless of causality, occurring in greater than or equal to 2% of patients for which the incidence was greater than in the placebo treatment group with neuropathic pain associated with spinal cord injury in the controlled trials. A majority of pregabalin-treated patients in clinical studies experienced adverse reactions with a maximum intensity of "mild" or "moderate".
| System Organ Class Preferred term | PGB *(N=182) | Placebo (N=174) |
|---|---|---|
| % | % | |
| ||
| Ear and labyrinth disorders | ||
| Vertigo | 2.7 | 1.1 |
| Eye disorders | ||
| Vision blurred | 6.6 | 1.1 |
| Gastrointestinal disorders | ||
| Dry mouth | 11.0 | 2.9 |
| Constipation | 8.2 | 5.7 |
| Nausea | 4.9 | 4.0 |
| Vomiting | 2.7 | 1.1 |
| General disorders and administration site conditions | ||
| Fatigue | 11.0 | 4.0 |
| Edema peripheral | 10.4 | 5.2 |
| Edema | 8.2 | 1.1 |
| Pain | 3.3 | 1.1 |
| Infections and infestations | ||
| Nasopharyngitis | 8.2 | 4.6 |
| Investigations | ||
| Weight increased | 3.3 | 1.1 |
| Blood creatine phosphokinase increased | 2.7 | 0 |
| Musculoskeletal and connective tissue disorders | ||
| Muscular weakness | 4.9 | 1.7 |
| Pain in extremity | 3.3 | 2.3 |
| Neck pain | 2.7 | 1.1 |
| Back pain | 2.2 | 1.7 |
| Joint swelling | 2.2 | 0 |
| Nervous system disorders | ||
| Somnolence | 35.7 | 11.5 |
| Dizziness | 20.9 | 6.9 |
| Disturbance in attention | 3.8 | 0 |
| Memory impairment | 3.3 | 1.1 |
| Paresthesia | 2.2 | 0.6 |
| Psychiatric disorders | ||
| Insomnia | 3.8 | 2.9 |
| Euphoric mood | 2.2 | 0.6 |
| Renal and urinary disorders | ||
| Urinary incontinence | 2.7 | 1.1 |
| Skin and subcutaneous tissue disorders | ||
| Decubitus ulcer | 2.7 | 1.1 |
| Vascular disorders | ||
| Hypertension | 2.2 | 1.1 |
| Hypotension | 2.2 | 0 |
Other Adverse Reactions Observed During the Clinical Studies of Pregabalin
Following is a list of treatment-emergent adverse reactions reported by patients treated with pregabalin during all clinical trials. The listing does not include those events already listed in the previous tables or elsewhere in labeling, those events for which a drug cause was remote, those events which were so general as to be uninformative, and those events reported only once which did not have a substantial probability of being acutely life-threatening.
Events are categorized by body system and listed in order of decreasing frequency according to the following definitions: frequentadverse reactions are those occurring on one or more occasions in at least 1/100 patients; infrequentadverse reactions are those occurring in 1/100 to 1/1,000 patients; rarereactions are those occurring in fewer than 1/1,000 patients. Events of major clinical importance are described in the Warnings and Precautions section (5).
Body as a Whole – Frequent:Abdominal pain, Allergic reaction, Fever, Infrequent:Abscess, Cellulitis, Chills, Malaise, Neck rigidity, Overdose, Pelvic pain, Photosensitivity reaction, Rare:Anaphylactoid reaction, Ascites, Granuloma, Hangover effect, Intentional Injury, Retroperitoneal Fibrosis, Shock
Cardiovascular System – Infrequent:Deep thrombophlebitis, Heart failure, Hypotension, Postural hypotension, Retinal vascular disorder, Syncope; Rare:ST Depressed, Ventricular Fibrillation
Digestive System – Frequent:Gastroenteritis, Increased appetite; Infrequent:Cholecystitis, Cholelithiasis, Colitis, Dysphagia, Esophagitis, Gastritis, Gastrointestinal hemorrhage, Melena, Mouth ulceration, Pancreatitis, Rectal hemorrhage, Tongue edema; Rare:Aphthous stomatitis, Esophageal Ulcer, Periodontal abscess
Hemic and Lymphatic System – Frequent:Ecchymosis; Infrequent:Anemia, Eosinophilia, Hypochromic anemia, Leukocytosis, Leukopenia, Lymphadenopathy, Thrombocytopenia; Rare:Myelofibrosis, Polycythemia, Prothrombin decreased, Purpura, Thrombocythemia, Alanine aminotransferase increased, Aspartate aminotransferase increased
Metabolic and Nutritional Disorders – Rare:Glucose Tolerance Decreased, Urate Crystalluria
Musculoskeletal System – Frequent:Arthralgia, Leg cramps, Myalgia, Myasthenia; Infrequent:Arthrosis; Rare:Chondrodystrophy, Generalized Spasm
Nervous System – Frequent:Anxiety, Depersonalization, Hypertonia, Hypoesthesia, Libido decreased, Nystagmus, Paresthesia, Sedation, Stupor, Twitching; Infrequent:Abnormal dreams, Agitation, Apathy, Aphasia, Circumoral paresthesia, Dysarthria, Hallucinations, Hostility, Hyperalgesia, Hyperesthesia, Hyperkinesia, Hypokinesia, Hypotonia, Libido increased, Myoclonus, Neuralgia; Rare:Addiction, Cerebellar syndrome, Cogwheel rigidity, Coma, Delirium, Delusions, Dysautonomia, Dyskinesia, Dystonia, Encephalopathy, Extrapyramidal syndrome, Guillain-Barré syndrome, Hypalgesia, Intracranial hypertension, Manic reaction, Paranoid reaction, Peripheral neuritis, Personality disorder, Psychotic depression, Schizophrenic reaction, Sleep disorder, Torticollis, Trismus
Respiratory System – Rare:Apnea, Atelectasis, Bronchiolitis, Hiccup, Laryngismus, Lung edema, Lung fibrosis, Yawn
Skin and Appendages – Frequent:Pruritus, Infrequent:Alopecia, Dry skin, Eczema, Hirsutism, Skin ulcer, Urticaria, Vesiculobullous rash; Rare:Angioedema, Exfoliative dermatitis, Lichenoid dermatitis, Melanosis, Nail Disorder, Petechial rash, Purpuric rash, Pustular rash, Skin atrophy, Skin necrosis, Skin nodule, Stevens-Johnson syndrome, Subcutaneous nodule
Special senses – Frequent:Conjunctivitis, Diplopia, Otitis media, Tinnitus; Infrequent:Abnormality of accommodation, Blepharitis, Dry eyes, Eye hemorrhage, Hyperacusis, Photophobia, Retinal edema, Taste loss, Taste perversion; Rare:Anisocoria, Blindness, Corneal ulcer, Exophthalmos, Extraocular palsy, Iritis, Keratitis, Keratoconjunctivitis, Miosis, Mydriasis, Night blindness, Ophthalmoplegia, Optic atrophy, Papilledema, Parosmia, Ptosis, Uveitis
Urogenital System – Frequent:Anorg*smia, Impotence, Urinary frequency, Urinary incontinence; Infrequent:Abnormal ejacul*tion, Albuminuria, Amenorrhea, Dysmenorrhea, Dysuria, Hematuria, Kidney calculus, Leukorrhea, Menorrhagia, Metrorrhagia, Nephritis, Oliguria, Urinary retention, Urine abnormality; Rare:Acute kidney failure, Balanitis, Bladder Neoplasm, Cervicitis, Dyspareunia, Epididymitis, Female lactation, Glomerulitis, Ovarian disorder, Pyelonephritis
Comparison of Gender and Race
The overall adverse event profile of pregabalin was similar between women and men. There are insufficient data to support a statement regarding the distribution of adverse experience reports by race.
6.2 Postmarketing Experience
The following adverse reactions have been identified during postapproval use of pregabalin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Nervous System Disorders – Headache
Gastrointestinal Disorders – Nausea, Diarrhea
Reproductive System and Breast Disorders – Gynecomastia, Breast Enlargement
Skin and subcutaneous tissue disorders – Bullous pemphigoid
There are postmarketing reports of life-threatening or fatal respiratory depression in patients taking pregabalin with opioids or other CNS depressants, or in the setting of underlying respiratory impairment.
In addition, there are postmarketing reports of events related to reduced lower gastrointestinal tract function (e.g., intestinal obstruction, paralytic ileus, constipation) when pregabalin was co-administered with medications that have the potential to produce constipation, such as opioid analgesics.
