Qudexy XR - Drug Monograph

Introduction

Qudexy XR (topiramate) extended-release capsules are an antiepileptic drug formulation designed for once-daily administration. Developed as a therapeutic alternative to immediate-release topiramate, this formulation provides sustained plasma concentrations while potentially reducing peak-to-trough fluctuations. Qudexy XR is indicated for various neurological conditions and represents an important option in the management of seizure disorders and migraine prevention.

Mechanism of Action

Topiramate exhibits multiple mechanisms of action that contribute to its therapeutic effects:

• Voltage-sensitive sodium channel modulation
• Enhancement of gamma-aminobutyric acid (GABA) activity at GABA-A receptors
• Antagonism of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate glutamate receptors
• Weak inhibition of carbonic anhydrase isoenzymes (CA-II and CA-IV)
• These combined actions result in reduced neuronal excitability and stabilization of neuronal membranes.

Indications

FDA-approved indications:

• Monotherapy or adjunctive therapy for partial-onset seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome in patients aged 2 years and older
• Prophylaxis of migraine headaches in patients 12 years and older

Dosage and Administration

• Initial dose: 25-50 mg once daily
• Titration: Increase by 25-50 mg weekly
• Maintenance: 200-400 mg daily in divided doses (maximum 400 mg/day)

• Initial dose: 25 mg once daily
• Titration: Increase by 25-50 mg weekly
• Maintenance: 100-500 mg daily

• Initial dose: 25 mg once daily
• Titration: Increase by 25 mg weekly
• Maintenance: 100 mg daily (divided into two doses)

• Renal impairment (CrCl <70 mL/min): Reduce dose by 50%
• Hepatic impairment: Use with caution, consider dose reduction
• Geriatric patients: Initiate at lower end of dosing range
• Pediatric patients: Dosing based on weight (3-6 mg/kg/day)

• Swallow capsules whole; do not crush or chew
• May be taken with or without food
• If unable to swallow capsule, contents may be sprinkled on soft food

Pharmacokinetics

• Bioavailability: ~80%
• Tmax: 10-14 hours (extended-release formulation)
• Food effect: Minimal effect on absorption

• Protein binding: 15-41%
• Volume of distribution: 0.6-0.8 L/kg
• Crosses blood-brain barrier and placenta

• Hepatic metabolism: Minimal (20-30%)
• CYP enzymes: Minimal involvement
• Not extensively metabolized

• Half-life: 21 hours (extended-release formulation)
• Renal excretion: 70% unchanged drug
• Dialyzable: Yes (approximately 50%)

Contraindications

• Hypersensitivity to topiramate or any component of the formulation
• History of metabolic acidosis while taking topiramate
• Concomitant use with other carbonic anhydrase inhibitors

Warnings and Precautions

• May cause hyperchloremic, non-anion gap metabolic acidosis
• Monitor serum bicarbonate levels periodically

• May cause symptomatic visual changes
• Discontinue immediately if symptoms occur

• Cognitive impairment (word-finding difficulties, memory problems)
• Depression, anxiety, and mood changes
• Increased risk of suicidal thoughts and behaviors

• May decrease sweating and increase body temperature
• Particularly concerning in pediatric patients

• Category D: May cause fetal harm
• Increased risk of oral clefts in infants exposed during first trimester

• Increased risk of nephrolithiasis (2-4% of patients)
• Maintain adequate hydration

Drug Interactions

• Carbonic anhydrase inhibitors: Increased risk of metabolic acidosis and kidney stones
• CNS depressants: Additive sedative effects
• Oral contraceptives: Potential decreased efficacy (ethinyl estradiol levels may decrease)
• Phenytoin: Decreased topiramate levels (15-20% reduction)
• Valproic acid: Decreased topiramate levels (15% reduction)
• Metformin: Increased risk of metabolic acidosis

• Digoxin: Possible decreased digoxin levels
• Lithium: Possible increased lithium levels
• Amitriptyline: Possible increased amitriptyline levels

Adverse Effects

• Paresthesia
• Fatigue
• Dizziness
• Weight loss
• Cognitive impairment
• Nausea
• Diarrhea

• Anorexia
• Difficulty with memory
• Depression
• Anxiety
• Nephrolithiasis
• Vision problems

• Metabolic acidosis
• Acute myopia and secondary angle-closure glaucoma
• Oligohydrosis and hyperthermia
• Suicidal ideation and behavior
• Hyperammonemia with or without encephalopathy
• Hepatic failure (rare)

Monitoring Parameters

• Comprehensive metabolic panel (including bicarbonate)
• Complete blood count
• Weight and BMI
• Ophthalmologic examination
• Pregnancy test in women of childbearing potential

• Serum bicarbonate levels every 3-6 months
• Renal function (BUN, creatinine) annually
• Weight monitoring every 3-6 months
• Mental status assessment at each visit
• Monitoring for signs of glaucoma or vision changes
• Therapeutic drug monitoring (if indicated)

• Pediatric patients: Monitor growth and development
• Patients with renal impairment: More frequent renal function assessment
• Patients with hepatic impairment: Monitor liver function tests

Patient Education

• Take medication exactly as prescribed; do not stop abruptly
• Swallow capsules whole; do not crush or chew
• Report any vision changes immediately
• Maintain adequate hydration to reduce kidney stone risk
• Be aware of potential cognitive effects (memory problems, word-finding difficulties)
• Use effective contraception; discuss pregnancy planning with healthcare provider
• Avoid alcohol and other CNS depressants
• Report mood changes, depression, or suicidal thoughts immediately
• Be cautious when driving or operating machinery until effects are known
• Regular follow-up appointments are essential for monitoring

• Take as soon as remembered unless close to next dose
• Do not double doses

• Store at room temperature (20-25°C)
• Keep in original container with lid tightly closed
• Protect from moisture

References

1. FDA Prescribing Information: Qudexy XR (topiramate) extended-release capsules. Revised 2022. 2. Glauser TA, et al. Epilepsia. 2013;54(3):551-563. 3. Silberstein SD, et al. Headache. 2013;53(5):799-816. 4. Johannessen Landmark C, et al. Acta Neurol Scand. 2016;134(3):207-221. 5. Perucca E. CNS Drugs. 2016;30(9):787-801. 6. National Institute for Health and Care Excellence (NICE). Epilepsies: diagnosis and management. Clinical guideline CG137. 2021. 7. American Academy of Neurology. Practice parameter: migraine prevention in children and adolescents. Neurology. 2019;92(11):527-535.