Vyvanse and Testosterone Interaction: What Patients and Clinicians Need to Know

What the two labels say

The Vyvanse drug interactions section covers monoamine oxidase inhibitors (contraindicated), serotonergic drugs, CYP2D6 inhibitors, urinary alkalinizing and acidifying agents, and tricyclic antidepressants [1]. The Depo-Testosterone label covers oral anticoagulants, oxyphenbutazone, and a statement that androgens may lower blood glucose and insulin requirements in people with diabetes [2]. Testosterone is not in the first list and lisdexamfetamine is not in the second.

Absence from an interaction list does not establish that the pair is safe to combine. The labels do address blood pressure separately, and both drugs can raise it [1][2].

How each drug is cleared

Lisdexamfetamine is an inactive prodrug. Red blood cells split it into dextroamphetamine and l-lysine, and cytochrome P450 enzymes are not involved in that step [1]. Testosterone is inactivated mainly in the liver, and about 90% of a dose leaves in urine as glucuronic and sulfuric acid conjugates [2]. These are separate clearance routes.

That does not make the active metabolite interaction-free. The Vyvanse label says CYP2D6 inhibitors may raise exposure to dextroamphetamine, the active metabolite [1].

Blood pressure is where the two drugs meet

The Vyvanse label states that CNS stimulants raise blood pressure by a mean of about 2 to 4 mm Hg and heart rate by about 3 to 6 bpm, with larger increases in some patients, and says to monitor all treated patients for tachycardia and hypertension [1].

The Depo-Testosterone label states that testosterone can increase blood pressure, which can increase cardiovascular risk over time. It says to monitor blood pressure periodically, especially in men with hypertension, and that testosterone products are not recommended in patients with uncontrolled hypertension [2]. FDA reported that required ambulatory blood pressure studies confirmed a blood pressure increase with all testosterone products, class-wide [4].

Background on the heart question: TRAVERSE, a randomized trial in 5,246 men aged 45 to 80 with hypogonadism and existing or high cardiovascular risk, tested a daily 1.62% testosterone gel, not injections. Major adverse cardiovascular events occurred in 7.0% on testosterone versus 7.3% on placebo (hazard ratio 0.96, 95% CI 0.78 to 1.17) [5]. Whether the blood pressure effects of the two drugs add up has not been established.

Hematocrit: a testosterone effect

A network meta-analysis of 29 placebo-controlled trials in 3,393 men found every testosterone formulation raised mean hematocrit: intramuscular enanthate or cypionate by 4.0% (95% CI 2.9 to 5.1), oral testosterone undecanoate by 4.3%, gel by 3.0%, patch by 1.4%, and intramuscular undecanoate by 1.6% [3]. A review of the erythrocytosis literature describes the risk as well established with testosterone therapy and highest with short-acting injectables [6]. The Depo-Testosterone label lists polycythemia among adverse reactions [2].

The Endocrine Society guideline recommends monitoring symptoms, serum testosterone, hematocrit and prostate cancer risk during the first year of testosterone therapy [7].

Sexual function and fertility

The Vyvanse label reports erectile dysfunction in 2.6% of men taking Vyvanse versus 0% on placebo, and decreased libido in 1.4% versus 0%, in its adult ADHD trial [1].

On the testosterone side, the Depo-Testosterone label says exogenous testosterone inhibits pituitary luteinizing hormone and, at large doses, follicle stimulating hormone, so sperm production may be suppressed [2]. The Endocrine Society guideline recommends against starting testosterone therapy in men planning fertility in the near term [7].

Competitive athletes

Both drugs sit on the WADA Prohibited List. Lisdexamfetamine is named in category S6.A and is prohibited in-competition; testosterone is in S1 Anabolic Agents and is prohibited at all times. A prescription does not make either one permitted in WADA-governed sport without a Therapeutic Use Exemption [8][9].