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06. Renal Impairment and Addiction Pharmacotherapy: Adjusting Naltrexone, Acamprosate, Gabapentin, and Topiramate

Published on March 6, 2026 Certification expiration date: March 6, 2029

Kevin A. Sevarino, M.D.C.M., Ph.D.

Associate Clinical Professor of Psychiatry - Yale School of Medicine

Key Points

For gabapentin in renal impairment, reduce the dose stepwise with CKD severity (mild: ~450 mg/day, moderate: ~200 mg/day, severe: ~100 mg/day). Gabapentin is dialyzable. Add a supplemental dose after each hemodialysis session.
Topiramate can cause metabolic acidosis through carbonic anhydrase inhibition. This effect is additive to renal disease-associated acidosis. Monitor bicarbonate levels and reduce to half the standard dose when GFR falls below 60.
Acamprosate is contraindicated in severe renal impairment (CrCl <30 mL/min); halve the dose in moderate impairment. Disulfiram and naltrexone lack formal adjustment guidelines but require caution across all stages of CKD.

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Slides and Transcript

Slide 1 of 16

Now, let’s talk about how we adjust substance use disorder medications in patients with renal impairment.

Renal Impairment and Addiction Pharmacotherapy: Adjusting Naltrexone, Acamprosate, Gabapentin, and Topiramate Slide 1 of 16

Slide 2 of 16

Renal impairment itself is something you’re going to run into with people both with substance use disorders and without. There’s about a half million people on dialysis at any one time in the United States. Believe it or not, 1 in 7 United States adults have chronic kidney disease. Because those with substance use disorders have elevated rates of cardiovascular diseases, that cohort of those with SUD are at elevated risk of renal injury especially as we get older.

References:

The National Forum of ESRD Networks. (2025, March 31). Quarterly National ESRD Census. https://www.esrdnetworks.org
Centers for Disease Control and Prevention. (2023). Chronic kidney disease in the United States, 2023. Chronic Kidney Disease. https://tinyurl.com/ywx9an5j

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Slide 3 of 16

SUD itself can directly lead to acute kidney injury and chronic kidney disease including end-stage renal disease. For example, alcohol use disorder has been associated with nearly twice the incidence of chronic kidney disease.

References:

Li, D., Xu, J., Liu, F., Wang, X., Yang, H., & Li, X. (2019). Alcohol drinking and the risk of chronic kidney damage: A meta-analysis of 15 prospective cohort studies. Alcoholism: Clinical and Experimental Research, 43(7), 1360–1372. https://doi.org/10.1111/acer.14112
Pan, C., Ju, T. R., Lee, C. C., Chen, Y., Hsu, C., Hung, D., Chen, W., & Wang, I. (2018). Alcohol use disorder tied to development of chronic kidney disease: A nationwide database analysis. PLOS One, 13(9), e0203410. https://doi.org/10.1371/journal.pone.0203410

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Slide 4 of 16

Patients presenting to emergency rooms due to methamphetamine or cocaine intoxication have a high incidence of rhabdomyolysis-induced acute tubular necrosis, 1/3 of whom progress to renal failure. So not only opiate use disorder and alcohol use disorder but especially psychostimulant use disorders are prone to elevated risk of developing renal failure.

References:

Richards, J. R., Johnson, E. B., Stark, R. W., & Derlet, R. W. (1999). Methamphetamine abuse and rhabdomyolysis in the ED: a 5-year study. The American Journal of Emergency Medicine, 17(7), 681-685. https://doi.org/10.1016/s0735-6757(99)90159-6
Amanollahi, A., Moradi, M., & Asghari, M. (2023). Incidence of rhabdomyolysis occurrence in psychoactive substance intoxication: A systematic review and meta-analysis. Scientific Reports, 13, 45031. https://doi.org/10.1038/s41598-023-45031-4

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Slide 5 of 16

So let’s talk about how we adjust our medications. As I said in general, cardiovascular disease leads to increased risk of renal disease. So the first thing I’d like to address is smoking cessation pharmacotherapy. Chantix in the United States or varenicline is known to be substantially excreted by the kidney. So the risk of toxic reactions to the drug may be greater in those with impaired renal function, but in fact this has a wide therapeutic window and dosage adjustment isn’t recommended.

References:

Saeed, D., Reza, T., Shahzad, M. W., Karim Mandokhail, A., Bakht, D., Qizilbash, F. H., Silloca-Cabana, E. O., Ramadhan, A., & Bokhari, S. F. H. (2023). Navigating the crossroads: Understanding the link between chronic kidney disease and cardiovascular health. Cureus, 15(12), e51362. https://doi.org/10.7759/cureus.51362

Renal Impairment and Addiction Pharmacotherapy: Adjusting Naltrexone, Acamprosate, Gabapentin, and Topiramate Slide 5 of 16

Slide 6 of 16

Nicotine replacement therapy really hasn’t been studied much so no dosage adjustments, but watch for signs of too much like being jittery or headache. Now, bupropion, clearance is significantly lower in subjects with renal impairment. So dosage adjustment isn’t described but I would tend to limit dosing to about 150 mg a day, especially in moderate and severe renal impairment. There are some that actually would do this for mild renal impairment.

References:

Turpeinen, M., Koivuviita, N., Tolonen, A., Reponen, P., Lundgren, S., Miettunen, J., Metsärinne, K., Rane, A., Pelkonen, O., & Laine, K. (2007). Effect of renal impairment on the pharmacokinetics of bupropion and its metabolites. British Journal of Clinical Pharmacology, 64(2), 165–173. https://doi.org/10.1111/j.1365-2125.2007.02866.x
Nagler, E. V., Webster, A. C., Vanholder, R., & Zoccali, C. (2012). Antidepressants for depression in stage 3-5 chronic kidney disease: a systematic review of pharmacokinetics, efficacy and safety with recommendations by European Renal Best Practice (ERBP). Nephrology, Dialysis, Transplantation, 27(10), 3736–3745. https://doi.org/10.1093/ndt/gfs295

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Slide 7 of 16

How about for alcohol use disorder? With disulfiram because of the possibility of an accidental disulfiram alcohol reaction, use it with extreme caution in those with chronic and acute nephritis.

References:

Stokes, M., Patel, P., & Abdijadid, S. (2024, September 10). Disulfiram. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK459340/

Renal Impairment and Addiction Pharmacotherapy: Adjusting Naltrexone, Acamprosate, Gabapentin, and Topiramate Slide 7 of 16

Slide 8 of 16

Naltrexone is primary metabolite are excreted primarily in the urine so caution is recommended when you administer this drug in the presence of renal impairment. It’s not dialyzable by the way. The pharmacokinetics of injectable naltrexone are not altered in subjects with mild renal insufficiency. But those with moderate to severe renal insufficiency, caution is recommended.

References:

U.S. Food and Drug Administration. (2024). Naltrexone hydrochloride tablet — structured product labeling (SPL). https://tinyurl.com/2ahns9u8

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Slide 9 of 16

Acamprosate, here’s one that you would need to adjust. With moderate renal impairment, where creatinine clearance is 30 to 50 mL/min, a starting dose of half, 1333 mg tab t.i.d. is recommended. There are acamprosate calcium delayed-release tablets and those are contraindicated in those with severe renal impairment, which is a creatinine clearance of less than 30 mL/min. Sometimes, acute kidney failure has been reported with acamprosate calcium treatment.

References:

Scott, L. J., Figgitt, D. P., Keam, S. J., & Waugh, J. (2005). Acamprosate: A review of its use in the maintenance of abstinence in patients with alcohol dependence. CNS Drugs, 19(5), 445-464. https://doi.org/10.2165/00023210-200519050-00006

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Slide 10 of 16

Baclofen is excreted principally unchanged in the urine and so you may need a reduced dose.

References:

Viavonou, R., Perreault, M. M., Barriere, O., Shink, E., Tremblay, P. O., Larouche, R., et al. (2014). Pharmacokinetic characterization of baclofen in patients with chronic kidney disease: Dose adjustment recommendations. Journal of Clinical Pharmacology, 54, 584-592. https://doi.org/10.1002/jcph.247

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Slide 11 of 16

Now, the next slide is on gabapentin. If you’ve got mild renal impairment, that is 30 to 59 is your GFR, cut that in about a half. So you go from 900 to 400 a day. Moderate renal impairment is 15 to 29 for GFR, cut that in half again to 200 mg. And severe, which is a GFR of 15 or below and you’re considering dialyzing, that’s 100 mg. Remember, in the presence of progressive decrease of renal impairment you need to reduce the dose of gabapentin. Further, it is dialyzable. So it is recommended after dialysis that an extra dose of gabapentin be given. In the case of the lowest doses here, when we’re using hemodialysis, we add an extra dose of 125 mg of gabapentin after the hemodialysis to the daily dose of 100 mg that was with somebody with a GFR of 15 or under.

References:

U.S. Food and Drug Administration. (2017). Neurontin (gabapentin) prescribing information. https://tinyurl.com/5xv4jzjt

Renal Impairment and Addiction Pharmacotherapy: Adjusting Naltrexone, Acamprosate, Gabapentin, and Topiramate Slide 11 of 16

Slide 12 of 16

Topiramate can cause metabolic acidosis by carbonic anhydrase inhibition and bicarbonate loss. This can be additive to renal disease associated acidosis. So you’ve got two metabolic acidosises. Metabolic acidosis can occur at any time during treatment and especially during pregnancy it’s dangerous because it has adverse effects on the fetus. So use it carefully. Measure bicarbs if you’re going to use this agent in the presence of renal impairment.

References:

U.S. Food and Drug Administration. (2012). Topamax (topiramate) prescribing information. https://tinyurl.com/2j6z2cum

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Slide 13 of 16

We’ll also adjust the dose. With GFRs under 60, use 1/2 the usual adult dose. And once you get to moderate renal impairment, they say reduce by 42% the dose and in severe by 50%. So actually, they’re saying 1/2 all the way through. And hemodialysis clears most topiramate. So it is dialyzable.

References:

U.S. Food and Drug Administration. (2012). Topamax (topiramate) prescribing information. https://tinyurl.com/2j6z2cum

Renal Impairment and Addiction Pharmacotherapy: Adjusting Naltrexone, Acamprosate, Gabapentin, and Topiramate Slide 13 of 16

Slide 14 of 16

For MOUD, methadone pharmacokinetics haven’t been evaluated in patients with renal insufficiency. Since it and its metabolites are excreted in urine to a variable degree, it’s recommended we start with lower doses or use longer dosing intervals, and titrate it more slowly. It is not removed by hemodialysis. Buprenorphine doesn’t have a clear relationship with GFR, so renal impairment doesn’t really alter its pharmacokinetics.

References:

Dean, M. (2004). Opioids in renal failure and dialysis patients. Journal of Pain and Symptom Management, 28(5), 497-504. https://doi.org/10.1016/j.jpainsymman.2004.02.021
Böger, R. H. (2006). Renal impairment: a challenge for opioid treatment? The role of buprenorphine. Palliative Medicine, 20(Suppl 1), s17-s23.

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Slide 15 of 16

So the key points on chronic kidney disease and SUD medications: About 1 in 7 US adults have chronic kidney disease and these rates are elevated in those with substance use disorders. Both disulfiram and naltrexone are to be used with caution in those with renal impairment, and there are defined dosage guidelines for gabapentin and acamprosate.

Renal Impairment and Addiction Pharmacotherapy: Adjusting Naltrexone, Acamprosate, Gabapentin, and Topiramate Slide 15 of 16

Slide 16 of 16

For topiramate and bupropion, dose reductions are recommended in the presence of renal impairment.

Renal Impairment and Addiction Pharmacotherapy: Adjusting Naltrexone, Acamprosate, Gabapentin, and Topiramate Slide 16 of 16

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Next Section

07. COPD, Sleep Apnea, and Addiction Pharmacotherapy: Methadone, Buprenorphine, Gabapentin, and Baclofen

Learning Objectives:

Apply evidence-based dosing adjustments for naltrexone, buprenorphine, methadone, and disulfiram in patients with hepatic impairment, renal insufficiency, cardiovascular disease, and respiratory conditions.
Identify which medications for alcohol use disorder and opioid use disorder are safe, require dose modification, or should be avoided across specific comorbid conditions, including decompensated cirrhosis and severe renal disease.
Describe integrated care models for managing patients with co-occurring substance use disorders and medical comorbidities, including liver disease and infectious conditions.

Original Release Date: March 06, 2026
Expiration Date: March 06, 2029

Faculty: Kevin A. Sevarino, M.D.C.M., Ph.D.
Medical Editor: Tomás Abudarham, M.D.

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