Atomoxetine × Methylphenidate

Methylphenidate blocks the reuptake of noradrenaline and dopamine (methylphenidate summary of product characteristics, SmPC, Spanish Agency of Medicines and Medical Devices, AEMPS). Atomoxetine selectively blocks the noradrenaline transporter (atomoxetine SmPC, AEMPS). Both drugs raise blood pressure and heart rate, so the SmPCs of both ask for caution with other drugs that raise blood pressure. The atomoxetine SmPC also warns of possible synergistic or additive effects with drugs that act on noradrenaline (SmPCs of both drugs, AEMPS). In a study, giving atomoxetine with methylphenidate did not increase cardiovascular effects beyond those seen with methylphenidate alone (atomoxetine label, US Food and Drug Administration, FDA). No pharmacokinetic interaction is expected. Cytochrome P450 (CYP) enzymes play no clinically relevant part in methylphenidate metabolism, and methylphenidate does not inhibit them to a relevant extent (methylphenidate SmPC, AEMPS). Atomoxetine causes no clinically important inhibition or induction of the main CYP enzymes (atomoxetine FDA label).

In most people, heart rate and blood pressure rise moderately. With central nervous system stimulants, including methylphenidate, blood pressure rises by about 2–4 mm Hg and heart rate by about 3–6 beats per minute on average (methylphenidate label, US Food and Drug Administration, FDA). With atomoxetine, heart rate rises on average by less than 10 beats per minute and blood pressure by less than 5 mm Hg (atomoxetine summary of product characteristics, SmPC). Some people have larger rises. With atomoxetine, 8–12% of children and adolescents and 6–10% of adults had heart rate increases of 20 beats per minute or more and blood pressure increases of 15–20 mm Hg or more (atomoxetine SmPC). Palpitations, chest pain on exertion, unexplained fainting and shortness of breath can point to heart disease (atomoxetine SmPC).

Use the combination with caution. The summaries of product characteristics (SmPCs) of both drugs ask for caution with other drugs that raise blood pressure. The atomoxetine SmPC also asks for caution with drugs that act on noradrenaline (methylphenidate and atomoxetine SmPCs, Spanish Agency of Medicines and Medical Devices, AEMPS). In a study, atomoxetine did not add to the cardiovascular effects of methylphenidate, and the documents set no dose adjustment for this pair (atomoxetine label, US Food and Drug Administration, FDA). Before starting each drug, take a detailed history and examine the patient to look for heart disease (SmPCs of both drugs, AEMPS). Record pulse and blood pressure before treatment, after each dose change and then at least every 6 months (SmPCs of both drugs, AEMPS). If blood pressure rises markedly, review the atomoxetine treatment or the other drug that raises blood pressure (atomoxetine SmPC, AEMPS). Stop methylphenidate in case of recurrent tachycardia, arrhythmia or systolic blood pressure above the 95th percentile, and consider referral to a cardiologist (methylphenidate SmPC, AEMPS). If palpitations, chest pain on exertion, unexplained fainting or shortness of breath occur, refer the patient promptly to a cardiologist (atomoxetine SmPC, AEMPS). Both SmPCs count a concomitant drug that raises blood pressure as a risk factor for cerebrovascular events, so check for neurological signs and symptoms at every visit (SmPCs of both drugs, AEMPS).