NMN/NR and Bupropion Interaction: What You Need to Know Before Combining Them

Is there a known interaction between NMN or NR and bupropion?

Published human drug-interaction studies of NMN or NR with prescription drugs were not identified, and none involves bupropion [2].

The pathway information below comes from the Contrave prescribing information, which covers a naltrexone-plus-bupropion combination product rather than bupropion alone, and from a study of sustained-release bupropion. Effects and instructions can differ by bupropion product and formulation [1][4].

How is bupropion metabolized?

The Contrave label states that bupropion is primarily metabolized to hydroxybupropion by CYP2B6. It gives CYP2B6 examples for that combination: ticlopidine and clopidogrel raise bupropion exposure and lower hydroxybupropion exposure, while ritonavir, lopinavir and efavirenz lower bupropion exposure [1].

Bupropion also inhibits CYP2D6. In a repeated-measures study of 21 smokers, 13 took bupropion sustained-release 150 mg twice daily and 8 took placebo. The urinary dextromethorphan/dextrorphan ratio rose from 0.012 to 0.418 with bupropion; the placebo group moved from 0.009 to 0.017, which was not statistically significant. After treatment, 6 of the 13 bupropion-treated participants had ratios consistent with poor CYP2D6 metabolizer status, against none on placebo [4]. For the Contrave combination, the label reports that metoprolol AUC was about 4-fold higher and peak concentration about 2-fold higher [1].

What NMN and NR do in humans

Both are sold as dietary supplements; neither is FDA-approved [3]. Oral NMN and NR raise NAD+ in blood within weeks [7][8][9][10]. In a 30-person trial, 15 healthy adults received NMN 250 mg/day and 15 received placebo for 12 weeks; whole-blood NAD+ rose with NMN [7]. In a separate trial, 80 middle-aged adults were assigned to placebo or NMN 300, 600 or 900 mg/day for 60 days; blood NAD rose in all NMN groups, highest at 600 and 900 mg [8]. A six-week crossover trial in healthy middle-aged and older adults found that NR was well tolerated and increased NAD+ metabolism [9]. In 20 people with Parkinson's disease randomly assigned 1:1 to NR 1,500 mg twice daily or placebo for 4 weeks, blood NAD+ rose up to 5-fold [10].

Higher blood NAD+ did not reliably mean higher tissue NAD+. In a 21-day crossover study of 12 men aged 70 to 80, NR 1 g/day did not raise muscle NAD+ itself, although markers of NAD+ synthesis and nicotinamide clearance products rose, and mitochondrial bioenergetics were unchanged [6].

NMN has been tested at 250 mg/day and at 1,250 mg/day [7][11]. NR has been tested at 1,000 mg twice daily and at 1,500 mg twice daily [12][10]. These are doses studied, not recommended doses. Human safety data beyond about 12 weeks are limited, and the trials were small [2].

Seizure risk with bupropion

Bupropion's seizure risk is dose-related. The Zyban label reports about 0.1% (1 in 1,000) with sustained-release bupropion at doses up to 300 mg/day and about 0.4% (13 of 3,200) with immediate-release bupropion at 300 to 450 mg/day, with a steep rise above that range [5]. The Wellbutrin XL and Contrave labels list seizure disorder as a contraindication; the Contrave label also lists a history of seizures [1]. The Contrave label directs extreme caution with other drugs that lower the seizure threshold, naming antipsychotics, antidepressants, theophylline and systemic corticosteroids [1].

The short NMN and NR trials above reported no severe adverse events [11][10].

What the bupropion labels say to watch for

The labels carry a class boxed warning for suicidal thoughts and behavior, and it applies to every bupropion product, including those labeled for smoking cessation or weight management [1][5]. The Contrave label calls for monitoring blood pressure and heart rate, which can rise during treatment [1].