From the Guidelines
Loperamide can be dangerous in patients with opioid addiction, particularly when misused at high doses, and should be used with caution and close monitoring in this population. While loperamide (Imodium) is an over-the-counter medication used to treat diarrhea, it should be used with extreme caution in those with a history of opioid addiction. At recommended doses (2-4 mg initially, then 2 mg after each loose stool, not exceeding 8 mg daily for OTC use), loperamide acts primarily on the intestines with minimal central nervous system effects, as noted in a study published in the Alimentary Pharmacology and Therapeutics journal 1. However, some individuals with opioid addiction misuse loperamide at extremely high doses (50-400 mg daily) in attempts to achieve euphoria or manage withdrawal symptoms. These high doses can cause serious cardiac complications including QT interval prolongation, ventricular arrhythmias, and sudden cardiac death. Loperamide can also worsen constipation in patients taking other opioids.
Key considerations for the use of loperamide in patients with opioid addiction include:
- Screening for opioid use disorder before recommending loperamide
- Considering alternative anti-diarrheal medications when appropriate
- Educating patients about proper dosing and potential dangers of misuse
- Close monitoring for signs of misuse or addiction, as outlined in the Annual Review of Medicine journal 1
- Being aware of the potential for loperamide to worsen constipation in patients taking other opioids, as noted in the Annals of Oncology journal 1
Healthcare providers should be cautious when prescribing loperamide to patients with a history of opioid addiction and should consider the potential risks and benefits of treatment, as well as alternative treatment options. By taking a careful and informed approach to the use of loperamide in this population, healthcare providers can help to minimize the risks associated with its use and ensure the best possible outcomes for their patients.
From the FDA Drug Label
The use of higher than recommended loperamide hydrochloride doses may result in life-threatening cardiac, CNS and respiratory adverse reactions. Cases of overdosage with loperamide hydrochloride (chronic ingestion of doses ranging from 70 mg to 1600 mg daily; 4 to 100 times the recommended dose) have resulted in life-threatening cardiac adverse reactions, including QT/QTc and QRS interval prolongation, Torsades de Pointes, Brugada syndrome and other ventricular arrhythmias, syncope, cardiac arrest, and death Cases include patients who were abusing (using supratherapeutic doses in place of opioids to induce euphoria) or misusing (taking higher than recommended doses to control diarrhea or to prevent opioid withdrawal) loperamide Management Consider loperamide as a possible cause of cardiac arrhythmias in patients who may have a history of opioid abuse or recent ingestion of unknown drugs and in the differential diagnosis of unstable arrhythmias, prolonged QTc or QRS intervals, and Torsades de Pointes
Loperamide can be dangerous in patients with opioid addiction due to the risk of life-threatening cardiac, CNS, and respiratory adverse reactions, especially when taken in higher than recommended doses.
- Patients with a history of opioid abuse may be at increased risk of cardiac arrhythmias and other adverse reactions when taking loperamide.
- Naloxone may be used to reverse opioid-related toxicity, including CNS and respiratory depression, associated with loperamide overdosage 2.
From the Research
Loperamide and Opioid Addiction
- Loperamide is an over-the-counter, μ-opioid receptor agonist commonly used as an antidiarrheal agent, which has been reported to be misused in supratherapeutic doses to achieve euphoria and/or avoid opioid withdrawal 3, 4.
- There have been increasing reports of loperamide misuse, dependence, and mortality rate in the past few years from poison control centers, medical examiners' offices, and clinical settings 3, 4.
- Loperamide overdoses are a growing concern from both a forensic and clinical standpoint, and the frequency of reported cases will likely increase as awareness grows within the medical and toxicological communities 3.
Treatment of Opioid Use Disorder
- Medications demonstrated to be effective for opioid use disorder (OUD) are methadone, buprenorphine, and naltrexone, which act by suppressing opioid withdrawal symptoms, attenuating the effects of other opioids, or blocking the effects of opioid agonists 5, 6.
- Treatment with methadone and buprenorphine has the additional risk of diversion and misuse of medication, and new depot and implant formulations have been developed to address issues of safety and problems of poor treatment adherence 5.
- For people with OUD who do not respond to these treatments, there is accumulating evidence for supervised injectable opioid treatment, and take-home naloxone programs aim to prevent fatal overdose 5.
Risk Factors for Opioid-Use Disorder and Overdose
- Risk factors for opioid misuse or addiction include past or current substance abuse, untreated psychiatric disorders, younger age, and social or family environments that encourage misuse 7.
- Opioid mortality prevalence is higher in people who are middle aged and have substance abuse and psychiatric comorbidities, and suicides are probably undercounted or frequently misclassified in reports of opioid-related poisoning deaths 7.