Is Adderall Bad for Your Liver? What the Data Shows

How Adderall is metabolized

Adderall immediate-release tablets and Adderall XR capsules are separate products with separate labels; the label information below is from the tablet label [1][4].

Amphetamine is oxidized at the 4 position of the benzene ring to 4-hydroxyamphetamine, and on the side chain's alpha or beta carbon to alpha-hydroxy-amphetamine or norephedrine [1]. CYP2D6 is involved in forming 4-hydroxyamphetamine [1]. At normal urine pH about half a dose is recovered as alpha-hydroxy-amphetamine derivatives and 30% to 40% as unchanged amphetamine; alkaline urine reduces elimination and acidic urine increases it [1].

Is liver injury on the label?

The adverse reactions section lists cardiovascular, central nervous system, eye, gastrointestinal, allergic, endocrine, skin and musculoskeletal reactions, including rhabdomyolysis, intestinal ischemia, angioedema, Stevens-Johnson syndrome and toxic epidermal necrolysis [1]. Liver injury and raised transaminases are not among them [1].

The contraindications are amphetamine hypersensitivity and MAOI use, or within 14 days of stopping one, because of hypertensive crisis [1]. The boxed warning covers abuse, misuse and addiction, not the liver [1].

What the trials measured

A pediatric Adderall XR trial randomized 584 children aged 6 to 12 at 47 sites to 10, 20 or 30 mg once daily or placebo for 3 weeks. Symptom scores improved at every active dose, and safety was assessed by recording adverse events, laboratory tests and vital signs at each visit, with physical examinations and electrocardiograms at the start and end of the study [2]. The abstract does not report any liver-specific results [2].

Drugs that change amphetamine levels

Antacids and sodium bicarbonate raise amphetamine blood levels, and the label says co-administration with gastrointestinal alkalinizing agents should be avoided [1]. Acidifying agents such as ascorbic acid lower blood levels and efficacy [1]. CYP2D6 inhibitors may increase amphetamine exposure and the risk of serotonin syndrome [1].

If liver injury is suspected

The American College of Gastroenterology describes drug-induced liver injury as a diagnosis of exclusion that requires careful history taking and a work-up for competing causes [5].