What are the cautions and contraindications for Vyvanse (lisdexamfetamine), Concerta (methylphenidate), Biphentin (methylphenidate), and Adderall (amphetamine and dextroamphetamine)?

Contraindications and Cautions for ADHD Stimulant Medications

Absolute Contraindications (All Stimulants)

Do not prescribe any of these medications (Vyvanse, Concerta, Biphentin, Foquest, or Adderall) to patients with known hypersensitivity to amphetamine or methylphenidate products, or to patients currently taking MAOIs or within 14 days of stopping MAOIs. 1, 2

Specific Contraindications by Drug Class:

Amphetamine-based medications (Vyvanse, Adderall):

• Known hypersensitivity to amphetamine products 1
• Anaphylactic reactions, Stevens-Johnson Syndrome, angioedema, and urticaria have been observed in postmarketing reports 1
• Concurrent MAOI use or use within 14 days of stopping MAOIs (including linezolid or intravenous methylene blue) due to increased risk of hypertensive crisis 1

Methylphenidate-based medications (Concerta, Biphentin, Foquest):

• Known hypersensitivity to methylphenidate or other components 2
• Concurrent MAOI treatment or use within the preceding 14 days 2

Critical Cardiovascular Cautions

Screen all patients for cardiovascular risk factors before initiating any stimulant medication, as these drugs increase blood pressure, heart rate, and can prolong QT interval. 3

• Monitor for hypertension, tachycardia, and arrhythmias during treatment 3
• Exercise extreme caution in patients with pre-existing cardiac conditions, long QT syndrome, or family history of sudden cardiac death 3
• Stimulants produce similar peak increases in mean arterial blood pressure, heart rate, body temperature, and pupil size across all formulations 4

Drug-Drug Interaction Warnings

Never combine stimulants with MAOIs due to life-threatening hypertensive crisis risk. 1, 2

Serotonin Syndrome Risk:

• Combining stimulants (particularly amphetamines, and possibly methylphenidate) with other serotonergic drugs increases risk of serotonin syndrome 3
• High-risk combinations include: SSRIs, SNRIs, TCAs, tramadol, meperidine, methadone, fentanyl, dextromethorphan, St. John's wort, and illicit drugs (ecstasy, methamphetamine, cocaine, LSD) 3
• Symptoms manifest within 24-48 hours: mental status changes (confusion, agitation, anxiety), neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity), and autonomic hyperactivity (hypertension, tachycardia, arrhythmias, tachypnea, diaphoresis) 3
• Advanced symptoms include fever, seizures, arrhythmias, unconsciousness, and potential fatalities 3

When combining two non-MAOI serotonergic drugs, start the second drug at low dose, increase slowly, and monitor intensively for symptoms in the first 24-48 hours after dosage changes. 3

Pregnancy and Reproductive Considerations

Amphetamines (Vyvanse, Adderall) cross the placental barrier, and while not associated with major congenital malformations, they carry small increased risks for specific complications. 5

• Possible increased risk for gastroschisis (adjusted OR 3.0; 95% CI, 1.2-7.4) 5
• Possible increased risk for preeclampsia (adjusted RR 1.29; 95% CI, 1.11-1.49) 5
• Continued stimulant use in second half of pregnancy may increase risk of preterm birth (adjusted RR 1.30; 95% CI, 1.10-1.55) 5
• Monitor infants carefully for irritability, insomnia, and feeding difficulties if mother was taking amphetamines during pregnancy 5
• Possible increased risk for spontaneous abortion, though confounding by indication cannot be ruled out 5

Common Adverse Effects Requiring Monitoring

All stimulants produce similar adverse effect profiles, with agitation and tachycardia being most frequent. 6

• Agitation occurs in 19.8-25.1% of exposures across all formulations 6
• Tachycardia occurs in 19.2-23.9% of exposures 6
• Additional common effects: sweating, tremors, nervousness, insomnia or somnolence, dizziness, gastrointestinal disturbances 3
• Most adverse events are mild to moderate in severity 7

Abuse Potential Considerations

Immediate-release amphetamine formulations (Adderall IR) have the highest abuse potential, followed by extended-release amphetamines, with lisdexamfetamine (Vyvanse) having the lowest abuse risk among amphetamines. 6

• Odds of abuse/misuse for immediate-release dextroamphetamine/amphetamine is 2.3 times higher (95% CI: 2.0-2.4) than lisdexamfetamine 6
• Extended-release dextroamphetamine/amphetamine abuse/misuse odds are 1.9 times higher (95% CI: 1.7-2.2) than lisdexamfetamine 6
• Lisdexamfetamine is a prodrug requiring enzymatic hydrolysis of lysine from dextroamphetamine, making extraction of the stimulant component more difficult 5, 7
• Despite prodrug design, lisdexamfetamine produces similar peak ratings of potentially abuse-related subjective effects (drug liking, drug high, stimulation) compared to D-amphetamine when taken orally 4

Special Population Warnings

In children under 6 years, exploratory ingestion accounts for 93.4% of exposures; in children 6-12 years, therapeutic errors account for 65.6%; in adolescents and adults, suicide attempts (28.4%) and abuse (19.5%) are most common. 6

• Serious outcomes (moderate/major/death) occur in 21.2% of lisdexamfetamine exposures, 24.7% of extended-release amphetamine exposures, and 25.5% of immediate-release amphetamine exposures 6
• Long-term administration is not associated with increased incidence of adverse events or treatment discontinuation rates 8

Critical Monitoring Parameters

• Baseline and periodic cardiovascular assessment (blood pressure, heart rate, ECG if indicated) 3, 4
• Growth parameters in pediatric patients 8
• Mental status changes, particularly emergence of agitation, anxiety, or psychotic symptoms 3
• Signs of abuse, diversion, or misuse, especially in adolescents and adults 6
• Drug-drug interactions, particularly with serotonergic agents 3