QUDEXY XR SIDE EFFECTS
- Generic Name: topiramate extended-release capsules
- Brand Name: Qudexy XR
- Drug Class: Anticonvulsants, Other
SIDE EFFECTS
The following serious adverse reactions are discussed in more detail in other sections of the labeling:
- Acute Myopia and Secondary Angle Closure Glaucoma
- Visual Field Defects
- Oligohydrosis and Hyperthermia
- Metabolic Acidosis
- Suicidal Behavior and Ideation
- Cognitive/Neuropsychiatric Adverse Reactions
- Serious Skin Reactions
- Hyperammonemia and Encephalopathy (Without and With Concomitant Valproic Acid Use
- Kidney Stones
- Hypothermia With Concomitant Valproic Acid Use
The data described in section 6.1 were obtained using immediate-release topiramate tablets.
Clinical Trials Experience With Immediate-Release Topiramate
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 clinical practice.
Monotherapy Epilepsy
Adults 16 Years Of Age And Older
The most common adverse reactions in the controlled trial (Study 1) that occurred in adults in the 400 mg/day topiramate group and at an incidence higher (≥ 10%) than in the 50 mg/day group were: paresthesia, weight loss, and anorexia (see Table 5).
Approximately 21% of the 159 adult patients in the 400 mg/day group who received topiramate as monotherapy in Study 1 discontinued therapy due to adverse reactions. The most common (≥ 2% more frequent than low-dose 50 mg/day topiramate) adverse reactions causing discontinuation were difficulty with memory, fatigue, asthenia, insomnia, somnolence, and paresthesia.
Pediatric Patients 6 to 15 Years of Age
The most common adverse reactions in the controlled trial (Study 1) that occurred in pediatric patients in the 400 mg/day topiramate group and at an incidence higher (≥ 10%) than in the 50 mg/day group were fever and weight loss (see Table 5).
Approximately 14% of the 77 pediatric patients in the 400 mg/day group who received topiramate as monotherapy in the controlled clinical trial discontinued therapy due to adverse reactions. The most common (≥ 2% more frequent than in the 50 mg/day group) adverse reactions resulting in discontinuation in this trial were difficulty with concentration/attention, fever, flushing, and confusion.
Table 1 represents the incidence of adverse reactions occurring in at least 3% of the adult and pediatric patients treated with 400 mg/day immediate-release topiramate and occurring with greater incidence than 50 mg/day topiramate.
Table 1: Adverse Reactions in the High Dose Group as Compared to the Low Dose Group, in Monotherapy Epilepsy Trials (Study 1) in Adult and Pediatric Patients
| Age Group | ||||
| Pediatric (6 to 15 Years) |
Adult (Age ≥16 Years) |
|||
| Immediate-release Topiramate Daily Dosage Group (mg/day) | ||||
| 50 | 400 | 50 | 400 | |
| Body System/ Adverse Reaction | (N=74) % | (N=77) % |
(N=160) % |
(N=159) % |
| Body as a Whole-General Disorders | ||||
| Asthenia | 0 | 3 | 4 | 6 |
| Fever | 1 | 12 | ||
| Leg pain | 2 | 3 | ||
| Central & Peripheral Nervous System Disorders | ||||
| Paresthesia | 3 | 12 | 21 | 40 |
| Dizziness | 13 | 14 | ||
| Ataxia | 3 | 4 | ||
| Hypoesthesia | 4 | 5 | ||
| Hypertonia | 0 | 3 | ||
| Involuntary Muscle contraction | 0 | 3 | ||
| Vertigo | 0 | 3 | ||
| Gastro-Intestinal System Disorders | ||||
| Constipation | 1 | 4 | ||
| Diarrhea | 8 | 9 | ||
| Gastritis | 0 | 3 | ||
| Dry mouth | 1 | 3 | ||
| Liver and Biliary System Disorders | ||||
| Increase in Gamma-GT | 1 | 3 | ||
| Metabolic and Nutritional Disorders | ||||
| Weight loss | 7 | 17 | 6 | 17 |
| Platelet, Bleeding & Clotting Disorders | ||||
| Epistaxis | 0 | 4 | ||
| Psychiatric Disorders | ||||
| Anorexia | 4 | 14 | ||
| Anxiety | 4 | 6 | ||
| Cognitive problems | 1 | 6 | 1 | 4 |
| Confusion | 0 | 3 | ||
| Depression | 0 | 3 | 7 | 9 |
| Difficulty with concentration or attention | 7 | 10 | 7 | 8 |
| Difficulty with memory | 1 | 3 | 6 | 11 |
| Insomnia | 8 | 9 | ||
| Decrease in libido | 0 | 3 | ||
| Mood problems | 1 | 8 | 2 | 5 |
| Personality disorder (behavior problems) | 0 | 3 | ||
| Psychomotor slowing | 3 | 5 | ||
| Somnolence | 10 | 15 | ||
| Red Blood Cell Disorders | ||||
| Anemia | 1 | 3 | ||
| Reproductive Disorders, Female | ||||
| Intermenstrual bleeding | 0 | 3 | ||
| Vaginal hemorrhage | 0 | 3 | ||
| Resistance Mechanism Disorders | ||||
| Infection | 3 | 8 | 2 | 3 |
| Viral infection | 3 | 6 | 6 | 8 |
| Respiratory System Disorders | ||||
| Bronchitis | 1 | 5 | 3 | 4 |
| Upper respiratory tract infection | 16 | 18 | ||
| Rhinitis | 5 | 6 | 2 | 4 |
| Sinusitis | 1 | 4 | ||
| Skin and Appendages Disorders | ||||
| Alopecia | 1 | 4 | 3 | 4 |
| Pruritus | 1 | 4 | ||
| Rash | 3 | 4 | 1 | 4 |
| Acne | 2 | 3 | ||
| Special Senses Other, Disorders | ||||
| Taste perversion | 3 | 5 | ||
| Urinary System Disorders | ||||
| Cystitis | 1 | 3 | ||
| Micturition frequency | 0 | 3 | ||
| Renal calculus | 0 | 3 | ||
| Urinary incontinence | 1 | 3 | ||
| Vascular (Extracardiac) Disorders | ||||
| Flushing | 0 | 5 | ||
Adjunctive Therapy Epilepsy
Adults 16 Years of Age and Older
In pooled controlled clinical trials in adults with partial-onset seizures, primary generalized tonic-clonic seizures, or Lennox-Gastaut syndrome, 183 patients received adjunctive therapy with immediate-release topiramate at dosages of 200 to 400 mg/day (recommended dosage range) and 291 patients received placebo. Patients in these trials were receiving 1 to 2 concomitant antiepileptic drugs in addition to immediate-release topiramate or placebo.
The most common adverse reactions in the controlled clinical trial that occurred in adult patients in the 200 to 400 mg/day topiramate group with an incidence higher (≥ 10%) than in the placebo group were: dizziness, speech disorders/related speech problems, somnolence, nervousness, psychomotor slowing, and vision abnormal (Table 6).
Table 2 presents the incidence of adverse reactions occurring in at least 3% of adult patients treated with 200 to 400 mg/day topiramate and was greater than placebo incidence. The incidence of some adverse reactions (e.g., fatigue, dizziness, paresthesia, language problems, psychomotor slowing, depression, difficulty with concentration/attention, mood problems) was dose-related and much greater at higher than recommended topiramate dosing (i.e., 600 mg to 1000 mg daily) compared to the incidence of these adverse reactions at the recommended dosing (200 mg to 400 mg daily) range.
Table 2: Most Common Adverse Reactions in Pooled Placebo-Controlled, Adjunctive Epilepsy Trials in Adultsa
| Body System/ Adverse Reaction |
Placebo (N=291) |
Topiramate Dosage (mg/day) |
| 200 to 400 (N=183) |
||
| Body as a Whole-General Disorders | ||
| Fatigue | 13 | 15 |
| Asthenia | 1 | 6 |
| Back pain | 4 | 5 |
| Chest pain | 3 | 4 |
| Influenza-like symptoms | 2 | 3 |
| Central & Peripheral Nervous System Disorders | ||
| Dizziness | 15 | 25 |
| Ataxia | 7 | 16 |
| Speech disorders/Related speech problems | 2 | 13 |
| Paresthesia | 4 | 11 |
| Nystagmus | 7 | 10 |
| Tremor | 6 | 9 |
| Language problems | 1 | 6 |
| Coordination abnormal | 2 | 4 |
| Gait abnormal | 1 | 3 |
| Gastro-Intestinal System Disorders | ||
| Nausea | 8 | 10 |
| Dyspepsia | 6 | 7 |
| Abdominal pain | 4 | 6 |
| Constipation | 2 | 4 |
| Metabolic and Nutritional Disorders | ||
| Weight loss | 3 | 9 |
| Psychiatric Disorders | ||
| Somnolence | 12 | 29 |
| Nervousness | 6 | 16 |
| Psychomotor slowing | 2 | 13 |
| Difficulty with memory | 3 | 12 |
| Confusion | 5 | 11 |
| Anorexia | 4 | 10 |
| Difficulty with concentration/attention | 2 | 6 |
| Mood problems | 2 | 4 |
| Agitation | 2 | 3 |
| Aggressive reaction | 2 | 3 |
| Emotional lability | 1 | 3 |
| Cognitive problems | 1 | 3 |
| Reproductive Disorders | ||
| Breast pain | 2 | 4 |
| Respiratory System Disorders | ||
| Rhinitis | 6 | 7 |
| Pharyngitis | 2 | 6 |
| Sinusitis | 4 | 5 |
| Vision Disorders | ||
| Vision abnormal | 2 | 13 |
| Diplopia | 5 | 10 |
| a Patients in these adjunctive trials were receiving 1 to 2 concomitant antiepileptic drugs in addition to topiramate or placebo | ||
In controlled clinical trials in adults, 11% of patients receiving immediate-release topiramate 200 to 400 mg/day as adjunctive therapy discontinued due to adverse reactions. This rate appeared to increase at dosages above 400 mg/day. Adverse reactions associated with discontinuing therapy included somnolence, dizziness, anxiety, difficulty with concentration or attention, fatigue, and paresthesia.
Pediatric Patients 2 to 15 Years of Age
In pooled, controlled clinical trials in pediatric patients (2 to 15 years of age) with partial-onset seizures, primary generalized tonic-clonic seizures, or Lennox-Gastaut syndrome, 98 patients received adjunctive therapy with immediate-release topiramate at dosages of 5 mg to 9 mg/kg/day (recommended dose range) and 101 patients received placebo.
The most common adverse reactions in the controlled clinical trial that occurred in pediatric patients in the 5 mg to 9 mg/kg/day immediate-release topiramate group with an incidence higher (≥ 10%) than in the placebo group were: fatigue and somnolence (see Table 7).
Table 3 presents the incidence of adverse reactions that occurred in at least 3% of pediatric patients 2 to 15 years of age receiving 5 mg to 9 mg/kg/day (recommended dose range) of immediate-release topiramate and was greater than placebo incidence.
Table 3: Adverse Reactions in Pooled Placebo-Controlled, Adjunctive Epilepsy Trials in Pediatric Patients 2 to 15 Years of Agea,b
| Body System/ Adverse Reaction |
Placebo (N=101) |
Topiramate (N=98) |
| Body as a Whole-General Disorders | ||
| Fatigue | 5 | 16 |
| Injury | 13 | 14 |
| Central & Peripheral Nervous System Disorders | ||
| Gait abnormal | 5 | 8 |
| Ataxia | 2 | 6 |
| Hyperkinesia | 4 | 5 |
| Dizziness | 2 | 4 |
| Speech disorders/Related speech problems | 2 | 4 |
| Gastro-Intestinal System Disorders | ||
| Nausea | 5 | 64 |
| Saliva increased | 4 | 6 |
| Constipation | 4 | 5 |
| Gastroenteritis | 2 | 3 |
| Metabolic and Nutritional Disorders | ||
| Weight loss | 1 | 9 |
| Platelet, Bleeding, & Clotting Disorders | ||
| Purpura | 4 | 8 |
| Epistaxis | 1 | 4 |
| Psychiatric Disorders | ||
| Somnolence | 16 | 26 |
| Anorexia | 15 | 24 |
| Nervousness | 7 | 14 |
| Personality disorder (behavior problems) | 9 | 11 |
| Difficulty with concentration/attention | 2 | 10 |
| Aggressive reaction | 4 | 9 |
| Insomnia | 7 | 8 |
| Difficulty with memory | 0 | 5 |
| Confusion | 3 | 4 |
| Psychomotor slowing | 2 | 3 |
| Resistance Mechanism Disorders | ||
| Infection viral | 3 | 7 |
| Respiratory System Disorders | ||
| Pneumonia | 1 | 5 |
| Skin and Appendages Disorders | ||
| Skin disorder | 2 | 3 |
| Urinary System Disorders | ||
| Urinary incontinence | 2 | 4 |
| a Patients in these adjunctive trials were receiving 1 to 2 concomitant antiepileptic drugs in addition to topiramate or placebo bValues represent the percentage of patients reporting a given adverse reaction. Patients may have reported more than one adverse reaction during the study and can be included in more than one adverse reaction category. |
||
None of the pediatric patients who received topiramate adjunctive therapy at 5 to 9 mg/kg/day in controlled clinical trials discontinued due to adverse reactions.
Migraine
Adults
In the four multicenter, randomized, double-blind, placebo-controlled, parallel group migraine clinical trials for the preventive treatment of migraine (which included 35 adolescent patients age 12 to 15 years of age), most of the adverse reactions with topiramate were mild or moderate in severity. Most adverse reactions occurred more frequently during the titration period than during the maintenance period.
The most common adverse reactions with immediate-release topiramate 100 mg in clinical trials for the preventive treatment of migraine of predominantly adults that were seen at an incidence higher (≥5%) than in the placebo group were paresthesia, anorexia, weight loss, taste perversion, diarrhea, difficulty with memory, hypoesthesia, and nausea (see Table 4).
Table 4 includes those adverse reactions that occurred in the placebo-controlled trials where the incidence in any immediate-release topiramate treatment group was at least 3% and was greater than that for placebo patients. The incidence of some adverse reactions (e.g., fatigue, dizziness, somnolence, difficulty with memory, difficulty with concentration/attention) was dose-related and greater at higher than recommended topiramate dosing (200 mg daily) compared to the incidence of these adverse reactions at the recommended dosing (100 mg daily).
Table 4: Adverse Reactions in Pooled, Placebo-Controlled, Migraine Trials in Adultsa,b
| Body System/ Adverse Reaction |
Placebo (N=445) % |
Topiramate Dosage (mg/day) | |
| 50 (N=235) % |
100 (N=386) % |
||
| Body as a Whole-General Disorders | |||
| Fatigue | 11 | 14 | 15 |
| Injury | 7 | 9 | 6 |
| Central & Peripheral Nervous System Disorders | |||
| Paresthesia | 6 | 35 | 51 |
| Dizziness | 10 | 8 | 9 |
| Hypoesthesia | 2 | 6 | 7 |
| Language problems | 2 | 7 | 6 |
| Gastro-Intestinal System Disorders | |||
| Nausea | 8 | 9 | 13 |
| Diarrhea | 4 | 9 | 11 |
| Abdominal pain | 5 | 6 | 6 |
| Dyspepsia | 3 | 4 | 5 |
| Dry mouth | 2 | 2 | 3 |
| Gastroenteritis | 1 | 3 | 3 |
| Metabolic and Nutritional Disorders | |||
| Weight loss | 1 | 6 | 9 |
| Musculoskeletal System Disorders | |||
| Arthralgia | 2 | 7 | 3 |
| Psychiatric Disorders | |||
| Anorexia | 6 | 9 | 15 |
| Somnolence | 5 | 8 | 7 |
| Difficulty with memory | 2 | 7 | 7 |
| Insomnia | 5 | 6 | 7 |
| Difficulty with concentration/attention | 2 | 3 | 6 |
| Mood problems | 3 | 3 | 6 |
| Anxiety | 3 | 4 | 5 |
| Depression | 4 | 3 | 4 |
| Nervousness | 2 | 4 | 4 |
| Confusion | 2 | 2 | 3 |
| Psychomotor slowing | 1 | 3 | 2 |
| Reproductive Disorders, Female | |||
| Menstrual disorder | 2 | 3 | 2 |
| Reproductive Disorders, Male | |||
| Ejaculation premature | 0 | 3 | 0 |
| Resistance Mechanism Disorders | |||
| Viral infection | 3 | 4 | 4 |
| Respiratory System Disorders | |||
| Upper respiratory tract infection | 12 | 13 | 14 |
| Sinusitis | 6 | 10 | 6 |
| Pharyngitis | 4 | 5 | 6 |
| Coughing | 2 | 2 | 4 |
| Bronchitis | 2 | 3 | 3 |
| Dyspnea | 2 | 1 | 3 |
| Skin and Appendages Disorders | |||
| Pruritis | 2 | 4 | 2 |
| Special Sense Other, Disorders | |||
| Taste perversion | 1 | 15 | 8 |
| Urinary System Disorders | |||
| Urinary tract infection | 2 | 4 | 2 |
| Vision Disorders | |||
| Blurred visionc | 2 | 4 | 2 |
| a Includes 35 adolescent patients age 12 to 15 years. b Values represent the percentage of patients reporting a given adverse reaction. Patients may have reported more than one adverse reaction during the study and can be included in more than one adverse reaction category. c Blurred vision was the most common term considered as vision abnormal. Blurred vision was an included term that accounted for >50% of reactions coded as vision abnormal, a preferred term. |
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Of the 1135 patients exposed to immediate-release topiramate in the adult placebo-controlled studies, 25% discontinued due to adverse reactions, compared to 10% of the 445 placebo-treated patients. The adverse reactions associated with discontinuing therapy in the immediate-release topiramate-treated patients in these studies included paresthesia (7%), fatigue (4%), nausea (4%), difficulty with concentration/attention (3%), insomnia (3%), anorexia (2%), and dizziness (2%).
Patients treated in these studies experienced mean percent reductions in body weight that were dose-dependent. This change was not seen in the placebo group. Mean changes of 0%, -2%, -3%, and -4% were seen for the placebo group, immediate-release topiramate 50 mg, 100 mg, and 200 mg groups, respectively.
Pediatric Patients 12 to 17 Years of Age
In five, randomized, double-blind, placebo-controlled, parallel group clinical trials for the preventive treatment of migraine, most of the adverse reactions with immediate-release topiramate occurred more frequently during the titration period than during the maintenance period. Among adverse reactions with onset during titration, approximately half persisted into the maintenance period.
In four, fixed-dose, double-blind clinical trials for the preventive treatment of migraine in immediate-release topiramate-treated pediatric patients 12 to 17 years of age, the most common adverse reactions immediate-release topiramate 100 mg that were seen at an incidence higher (≥ 5%) than in the placebo group were: paresthesia, upper respiratory tract infection, anorexia, and abdominal pain (see Table 9). Table 9 shows adverse reactions from the pediatric trial (Study 13) in which 103 pediatric patients were treated with placebo or 50 mg or 100 mg of immediate-release topiramate, and three predominantly adult trials in which 49 pediatric patients (12 to 17 years of age) were treated with placebo or 50 mg, 100 mg, or 200 mg of immediate-release topiramate. Table 9 also shows adverse reactions in pediatric patients in the controlled migraine trials when the incidence in an immediate-release topiramate dose group was at least 5% or higher and greater than the incidence of placebo. Many adverse reactions shown in Table 5 indicated a dose-dependent relationship. The incidence of some adverse reactions (e.g., allergy, fatigue, headache, anorexia, insomnia, somnolence, and viral infection) was dose-related and greater at higher than recommended immediate-release topiramate dosing (200 mg daily) compared to the incidence of these adverse reactions at the recommended dose (100 mg daily).
Table 5: Adverse Reactions in Pooled, Double-Blind Studies for the Preventive Treatment of Migraine in Pediatric Patients 12 to 17 Years of Agea,b,c
| Body System/ Adverse Reaction |
Placebo (N=45) % |
Topiramate Dosage | |
| 50 mg/day (N=46) % |
100 mg/day (N=48) % |
||
| Body as a Whole-General Disorders | |||
| Fatigue | 7 | 7 | 8 |
| Fever | 2 | 4 | 6 |
| Central & Peripheral Nervous System Disorders | |||
| Paresthesia | 7 | 20 | 19 |
| Dizziness | 4 | 4 | 6 |
| Gastro-Intestinal System Disorders | |||
| Abdominal pain | 9 | 7 | 15 |
| Nausea | 4 | 4 | 8 |
| Metabolic and Nutritional Disorders | |||
| Weight loss | 2 | 7 | 4 |
| Psychiatric Disorders | |||
| Anorexia | 4 | 9 | 10 |
| Somnolence | 2 | 2 | 6 |
| Insomnia | 2 | 9 | 2 |
| Resistance Mechanism Disorders | |||
| Infection viral | 4 | 4 | 8 |
| Respiratory System Disorders | |||
| Upper respiratory tract infection | 11 | 26 | 23 |
| Rhinitis | 2 | 7 | 6 |
| Sinusitis | 2 | 9 | 4 |
| Coughing | 0 | 7 | 2 |
| Special Senses Other, Disorders | |||
| Taste perversion | 2 | 2 | 6 |
| Vision Disorders | |||
| Conjunctivitis | 4 | 7 | 4 |
| a 35 adolescent patients aged 12 to <16 years were also included in adverse reaction assessment for adults. b Incidence is based on the number of subjects experiencing at least 1 adverse event, not the number of events. cIncluded studies MIG-3006, MIGR-001, MIGR-002 and MIGR-003 |
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In the double-blind placebo-controlled studies, adverse reactions led to discontinuation of treatment in 8% of placebo patients compared with 6% of immediate-release topiramate-treated patients. Adverse reactions associated with discontinuing therapy that occurred in more than one immediate-release topiramate-treated patient were fatigue (1%), headache (1%), and somnolence (1%).
Increased Risk For Bleeding
Topiramate is associated with an increased risk for bleeding. In a pooled analysis of placebo-controlled studies of approved and unapproved indications, bleeding was more frequently reported as an adverse reaction for topiramate than for placebo (4.5% versus 3.0% in adult patients, and 4.4% versus 2.3% in pediatric patients). In this analysis, the incidence of serious bleeding events for topiramate and placebo was 0.3% versus 0.2% for adult patients, and 0.4% versus 0% for pediatric patients.
Adverse bleeding reactions reported with topiramate ranged from mild epistaxis, ecchymosis, and increased menstrual bleeding to life-threatening hemorrhages. In patients with serious bleeding events, conditions that increased the risk for bleeding were often present, or patients were often taking drugs that cause thrombocytopenia (other antiepileptic drugs) or affect platelet function or coagulation (e.g., aspirin, nonsteroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors, or warfarin or other anticoagulants).
Other Adverse Reactions Observed During Clinical Trials
Other adverse reactions seen during clinical trials were: abnormal coordination, eosinophilia, gingival bleeding, hematuria, hypotension, myalgia, myopia, postural hypotension, scotoma, suicide attempt, syncope, and visual field defect.
Laboratory Test Abnormalities
Adult Patients
In addition to changes in serum bicarbonate (i.e., metabolic acidosis), sodium chloride and ammonia, immediate-release topiramate was associated with changes in several clinical laboratory analytes in randomized, double-blind, placebo-controlled studies. Controlled trials of adjunctive topiramate treatment of adults for partial onset seizures showed an increased incidence of markedly decreased serum phosphorus (6% topiramate versus 2% placebo), markedly increased serum alkaline phosphatase (3% topiramate versus 1% placebo), and decreased serum potassium (0.4% topiramate versus 0.1% placebo).
Pediatric Patients
In pediatric patients (1 to 24 months) receiving adjunctive topiramate for partial-onset seizures, there was an increased incidence for an increased result (relative to normal analyte reference range) associated with topiramate (vs placebo) for the following clinical laboratory analytes: creatinine, BUN, alkaline phosphatase, and total protein. The incidence was also increased for a decreased result for bicarbonate (i.e., metabolic acidosis), and potassium with immediate-release (vs placebo). QUDEXY XR is not indicated for partial-onset seizures in pediatric patients less than 2 years of age.
In pediatric patients (ranging from 6 to 17 years of age) receiving immediate-release topiramate for the preventive treatment of migraine, there was an increased incidence for an increased result (relative to normal analyte reference range) associated with immediate-release topiramate (vs placebo) for the following clinical laboratory analytes: creatinine, BUN, uric acid, chloride, ammonia, alkaline phosphatase, total protein, platelets, and eosinophils, The incidence was also increased for a decreased result for phosphorus, bicarbonate, total white blood count, and neutrophils. QUDEXY XR is not indicated for the preventive treatment of migraine in pediatric patients less than 12 years of age.
Clinical Trials Experience With QUDEXY XR
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 clinical practice. In the QUDEXY XR study, a dose of 200 mg per day was administered to a limited number of patients; therefore, these results cannot be directly compared to immediate-release topiramate experience.
The safety data presented below are from 249 patients with partial epilepsy on concomitant AEDs who participated in the QUDEXY XR study.
Table 6 displays the incidence of adverse reactions that occurred in ≥2% of patients and numerically greater than placebo.
Table 6: Incidence (≥2%) of Adverse Reactions in Placebo-Controlled Adjunctive Therapy Clinical Trial in Patients With Partial-Onset Seizures
| Body System/ Adverse Reaction | Placebo (N=125) |
QUDEXY XR (200 mg) (N=124) |
| General Disorders | ||
| Fatigue | 5 | 6 |
| Asthenia | 1 | 2 |
| Irritability | 1 | 2 |
| Nervous System Disorders | ||
| Somnolence | 2 | 12 |
| Dizziness | 6 | 7 |
| Paresthesia | 2 | 7 |
| Aphasia | 0 | 2 |
| Dysarthria | 1 | 2 |
| Memory impairment | 1 | 2 |
| Psychiatric Disorder | ||
| Psychomotor retardation | 0 | 2 |
| Cardiovascular Disorders, General | ||
| Hypertension | 1 | 3 |
| Metabolic and Nutritional Disorders | ||
| Weight decrease | 0 | 7 |
| Decreased appetite | 2 | 4 |
| Anorexia | 1 | 2 |
In the controlled clinical study using QUDEXY XR, 8.9% of patients who received QUDEXY XR and 4.0% who received placebo discontinued as a result of adverse reactions.
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of immediate-release topiramate. 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.
Body as a Whole–General Disorders: oligohydrosis and hyperthermia, hyperammonemia, hyperammonemic encephalopathy, hypothermia with concomitant valproic acid.
Gastrointestinal System Disorders: hepatic failure (including fatalities), hepatitis, pancreatitis
Skin And Appendage Disorders: bullous skin reactions (including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), pemphigus.
Urinary System Disorders: kidney stones, nephrocalcinosis.
Vision Disorders: acute myopia, secondary angle closure glaucoma, maculopathy
Hematological Disorders: decrease of the International Normalized Ratio (INR) or prothrombin time when given concomitantly with Vitamin K antagonist anticoagulant medications such as warfarin.
SRC: NLM .