Can you prescribe fluvoxamine (Luvox) and lisdexamfetamine (Vyvanse)?

Can Fluvoxamine (Luvox) and Lisdexamfetamine (Vyvanse) Be Prescribed Together?

Yes, fluvoxamine and lisdexamfetamine can be prescribed together with appropriate monitoring, though this combination requires careful attention to drug interactions and cardiovascular effects. 1, 2

Critical Safety Considerations

Absolute Contraindications

• Never combine either medication with monoamine oxidase inhibitors (MAOIs) due to severe risk of hypertensive crisis and serotonin syndrome; a minimum 14-day washout after stopping an MAOI is required before starting either fluvoxamine or lisdexamfetamine. 1, 3, 4
• Fluvoxamine is specifically contraindicated with tizanidine due to a 33-fold increase in tizanidine exposure, causing severe hypotension and sedation. 1, 4
• Do not combine fluvoxamine with thioridazine, terfenadine, astemizole, cisapride, or pimozide due to QT prolongation and risk of fatal arrhythmias. 4
• Avoid in patients with symptomatic cardiovascular disease, uncontrolled hypertension, or active psychosis. 3

Drug Interaction Profile

• Fluvoxamine is a potent inhibitor of CYP1A2 and moderate inhibitor of CYP3A4 and CYP2C19, which can significantly increase levels of drugs metabolized by these pathways. 1, 5, 6
• The combination of fluvoxamine with lisdexamfetamine carries theoretical risk of serotonin syndrome when combining serotonergic medications (SSRIs) with stimulants, though clinical risk appears lower than theoretical concerns suggest. 2
• Fluvoxamine can increase plasma concentrations of tricyclic antidepressants, benzodiazepines (alprazolam, diazepam), theophylline, propranolol, and warfarin through enzyme inhibition. 1, 6

Monitoring Protocol

Baseline Assessment

• Obtain blood pressure and pulse measurements, as both medications can affect cardiovascular parameters. 7, 2, 3
• Perform comprehensive cardiac history including syncope, chest pain, palpitations, and family history of sudden death or arrhythmias. 7
• Screen for substance use risk, particularly with lisdexamfetamine due to its abuse potential. 7, 3

Ongoing Monitoring

• Monitor closely for serotonin syndrome symptoms during the first 24-48 hours after combining medications or any dose changes, including mental status changes (agitation, confusion), neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis, fever). 2
• Check blood pressure and pulse at each visit during titration and quarterly during maintenance. 7, 2
• Track sleep quality, appetite changes, and weight at every visit. 7
• Monitor for suicidality, particularly during the first few months or at dose changes. 7, 4

Dosing Strategy

Fluvoxamine Initiation

• Start fluvoxamine at 50 mg once daily at bedtime to minimize gastrointestinal side effects, particularly nausea. 5, 8
• Increase by 50 mg increments every 4-7 days as tolerated, up to 300 mg/day for adults. 5, 8
• Doses above 100 mg/day should be divided into two doses; if unequal, give the larger dose at bedtime. 8

Lisdexamfetamine Initiation

• Start lisdexamfetamine at 30 mg once daily in the morning with or without food. 3
• Titrate in increments of 10-20 mg at approximately weekly intervals up to maximum of 70 mg once daily. 3
• Avoid afternoon doses due to potential for insomnia. 3

Combined Therapy Approach

• Start with lower doses of both medications and increase gradually while monitoring for side effects, beginning with subtherapeutic "test" doses to assess tolerance. 2
• When combining, consider starting one medication first, achieving stable dosing, then adding the second medication to better identify which agent may be causing any adverse effects. 2

Common Pitfalls to Avoid

• Do not assume the combination is contraindicated simply because both affect serotonin; the actual clinical risk is manageable with proper monitoring. 2
• Do not overlook fluvoxamine's potent CYP1A2 inhibition when patients are taking other medications metabolized by this pathway (theophylline, clozapine, olanzapine, caffeine). 1, 6
• Do not abruptly discontinue fluvoxamine; taper gradually over 2-4 weeks by reducing dose in 2.5-5 mg increments to prevent discontinuation syndrome (dizziness, nausea, paresthesias, anxiety). 1, 9
• Avoid prescribing this combination in patients with seizure disorders without careful risk-benefit assessment, as both medications can lower seizure threshold. 2

Clinical Context

• Fluvoxamine demonstrates efficacy in obsessive-compulsive disorder, social anxiety disorder, panic disorder, and generalized anxiety disorder. 5, 8, 10
• Lisdexamfetamine is FDA-approved for ADHD in adults and children ≥6 years and for moderate-to-severe binge eating disorder in adults. 3
• The combination may be appropriate when treating comorbid ADHD with anxiety disorders, as stimulants do not necessarily worsen anxiety and may improve comorbid symptoms. 7
• Approximately 70-80% of patients with ADHD respond to stimulant therapy when properly titrated. 7