What drug interactions should be avoided or closely monitored in a patient taking Vyvanse (lisdexamfetamine)?

Drug Interactions with Vyvanse (Lisdexamfetamine)

Vyvanse is absolutely contraindicated with MAO inhibitors and must not be used within 14 days of the last MAO inhibitor dose due to risk of hypertensive crisis. 1

Absolute Contraindications

• MAO Inhibitors: Combining lisdexamfetamine with MAO inhibitors or using within 14 days of discontinuation can cause life-threatening hypertensive emergencies. 2, 1
• Known hypersensitivity to amphetamine products or any ingredient in lisdexamfetamine. 1

High-Risk Interactions Requiring Immediate Monitoring

Serotonergic Agents (Risk of Serotonin Syndrome)

• SSRIs, SNRIs, triptans, and other serotonergic drugs: When combined with Vyvanse, monitor immediately for agitation, tremor, sweating, dilated pupils, hyperreflexia, muscle rigidity, fever, and tachycardia. 3, 1
• If serotonin syndrome occurs: Discontinue all serotonergic agents immediately and initiate supportive treatment. 3, 1
• The risk is present even during overdosage situations without concomitant serotonergic agents. 1

Tricyclic Antidepressants (TCAs)

• Combining stimulants with TCAs may increase TCA serum levels, though recent evidence suggests this interaction may be less clinically significant than previously thought. 2
• Critical warning: One case report documented a 10-year-old death from cardiac arrhythmia while on dextroamphetamine and imipramine—review this risk with parents before combining. 2
• Exercise caution when combining; consider baseline ECG monitoring. 2

Moderate-Risk Interactions Requiring Dose Adjustments

Urinary pH Modifiers

• Acidifying agents (e.g., ascorbic acid, fruit juices): Decrease amphetamine blood levels by increasing renal excretion—may require dose increase of Vyvanse. 1
• Alkalinizing agents (e.g., sodium bicarbonate, antacids): Increase amphetamine blood levels by decreasing renal excretion—may require dose decrease of Vyvanse. 1
• Adjust lisdexamfetamine dosage accordingly based on clinical response. 1

Anticonvulsants

• Phenytoin and carbamazepine: Amphetamines can inhibit metabolism, potentially increasing anticonvulsant levels and side effects. 2
• Monitor anticonvulsant levels and adjust doses as needed. 2
• Note: Vyvanse does not lower seizure threshold once seizures are controlled with anticonvulsants. 2

Antihypertensive Agents

• Guanethidine: Amphetamines interact to produce paradoxical hypotension. 2
• Monitor blood pressure closely when combining with any antihypertensive medication. 1

Cardiovascular Monitoring Requirements

Avoid Vyvanse entirely in patients with:

• Known structural cardiac abnormalities 1
• Cardiomyopathy 1
• Serious cardiac arrhythmias 1
• Coronary artery disease 1
• Symptomatic cardiovascular disease 2, 1
• Hypertension (relative contraindication) 2
• Hyperthyroidism 2

For all patients on Vyvanse: Monitor blood pressure and pulse regularly, as the medication increases both parameters. 1

Psychiatric Contraindications and Monitoring

• Active psychotic disorder: Do not administer Vyvanse. 2
• Prior to initiating: Screen for risk factors for developing manic episodes. 1
• If new psychotic or manic symptoms occur: Consider discontinuing lisdexamfetamine. 1
• Tics and Tourette's syndrome: Before starting, assess family history and clinically evaluate for tics; regularly monitor for emergence or worsening. 1

Special Populations Requiring Caution

Substance Abuse History

• Use with great care if there is any history of drug abuse. 2
• Contraindicated in patients with history of illicit stimulant use/abuse unless in a controlled setting with close supervision. 2
• Adolescents: Assess for substance abuse symptoms before initiating; monitor for diversion (use for non-medical purposes). 2

Renal Impairment

• Severe renal impairment: Maximum dose is 50 mg/day. 1
• End-stage renal disease (ESRD): Maximum dose is 30 mg/day. 1

Pregnancy and Lactation

• May cause fetal harm; lisdexamfetamine is a prodrug converted to dextroamphetamine. 2, 1
• Breastfeeding not recommended—monitor infants for irritability, insomnia, and feeding difficulty if breastfeeding occurs. 2, 1

Lower-Risk Interactions

Oral Contraceptives

• Unlike rifamycins, amphetamines do not significantly reduce oral contraceptive efficacy through hepatic enzyme induction. 2
• No dose adjustment typically needed. 2

SSRIs (When Not Causing Serotonin Syndrome)

• SSRIs may be combined with stimulants for comorbid ADHD and depression, though based on algorithmic recommendations rather than controlled trials. 2
• 80% of methylphenidate metabolism is extrahepatic, explaining minimal pharmacokinetic interactions with SSRIs. 2
• Since lisdexamfetamine is converted to dextroamphetamine in red blood cells (not liver), similar low pharmacokinetic interaction risk applies. 4, 5

Common Pitfalls to Avoid

1. Forgetting the 14-day washout: Always wait 14 days after stopping an MAO inhibitor before starting Vyvanse. 1
2. Ignoring dietary factors: Acidic foods/drinks (orange juice, vitamin C) can significantly reduce Vyvanse effectiveness. 1
3. Overlooking cardiac screening: Even in young patients, screen for structural heart disease and family history of sudden cardiac death before prescribing. 1, 6
4. Missing serotonin syndrome early signs: The combination of stimulants with multiple serotonergic agents (common in psychiatric practice) requires vigilant monitoring. 3, 1