Vyvanse Liver Function Impact: What Patients and Clinicians Need to Know

What the label says about the liver

Vyvanse is approved for ADHD in adults and children 6 years and older and for moderate to severe binge eating disorder in adults [1]. Its only boxed warning is for abuse, misuse and addiction [1]. The warnings and precautions section covers serious cardiac disease, increases in blood pressure (mean about 2 to 4 mm Hg) and heart rate (mean about 3 to 6 bpm), psychiatric reactions, growth suppression in children, peripheral vasculopathy including Raynaud's phenomenon, serotonin syndrome, and tics or worsening Tourette's syndrome [1]. Liver injury is not on that list.

The label gives maximum doses of 50 mg/day for severe renal impairment (GFR 15 to under 30) and 30 mg/day for end-stage renal disease [1].

How the drug is switched on

Lisdexamfetamine is an inactive prodrug. The label states that red blood cells convert it to dextroamphetamine and l-lysine in blood, not by cytochrome P450 enzymes, and that the parent drug does not bind norepinephrine or dopamine reuptake sites in vitro [1]. Amphetamines block reuptake of norepinephrine and dopamine into the presynaptic neuron and increase release of these monoamines; the exact mode of therapeutic action in ADHD and binge eating disorder is not known [1].

About 96% of an oral dose is recovered in urine — 42% as amphetamine, 25% as hippuric acid and 2% as intact lisdexamfetamine — and dextroamphetamine's half-life is about 10 to 11.3 hours in healthy adults [1].

The label says CYP2D6 inhibitors may increase exposure to dextroamphetamine and add to serotonin syndrome risk, and it directs a lower starting dose with monitoring [1]. That entry concerns blood levels of the active metabolite, not liver damage.

Interactions the label lists

• MAO inhibitors are contraindicated during Vyvanse use and within 14 days of stopping one, because of hypertensive crisis; the label also describes toxic neurological effects and malignant hyperpyrexia with MAOIs [1].
• The label says urinary alkalinizing agents such as sodium bicarbonate can raise amphetamine blood levels and potentiate its effects, and it advises avoiding coadministration [1].
• The label says urinary acidifying agents such as ascorbic acid can lower amphetamine blood levels and efficacy and that the dose should be increased based on clinical response [1].
• Serotonergic drugs (SSRIs, SNRIs, triptans, tricyclics, lithium, tramadol, St. John's wort and others) and CYP2D6 inhibitors raise serotonin syndrome risk; the label directs lower starting doses and monitoring [1].

None of these entries is described by the label as a liver interaction. They concern amphetamine blood levels, serotonin risk and cardiovascular effects [1].

With existing liver disease

The label's contraindications are hypersensitivity to amphetamine products or other ingredients of Vyvanse, and use of an MAOI or within 14 days of stopping one [1]. Liver disease is not listed. The label's pretreatment assessments address cardiac disease — history, family history of sudden death or ventricular arrhythmia, and physical exam — and family history or signs of tics or Tourette's syndrome [1].