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Jaxon Evans
Jaxon Evans

Buy Loperamide Bulk

[1-30-2018] To foster safe use of the over-the counter (OTC) anti-diarrhea drug loperamide, the U.S. Food and Drug Administration (FDA) is working with manufacturers to use blister packs or other single dose packaging and to limit the number of doses in a package. We continue to receive reports of serious heart problems and deaths with much higher than the recommended doses of loperamide, primarily among people who are intentionally misusing or abusing the product, despite the addition of a warning to the medicine label and a previous communication. Loperamide is a safe drug when used as directed.

buy loperamide bulk


Patients and consumers should only take the dose of loperamide directed by your health care professionals or according to the OTC Drug Facts label, as taking more than prescribed or listed on the label can cause severe heart rhythm problems or death. If you are using OTC loperamide and your diarrhea lasts more than 2 days, stop taking the medicine and contact your health care professional.

Health care professionals should be aware that using much higher than recommended doses of loperamide, either intentionally or unintentionally, can result in serious cardiac adverse events, including QT interval prolongation, Torsades de Pointes or other ventricular arrhythmias, syncope, and cardiac arrest. In cases of abuse, individuals often use other drugs together with loperamide in attempts to increase its absorption and penetration across the blood-brain barrier, inhibit loperamide metabolism, and enhance its euphoric effects. Some individuals are taking high doses of loperamide to treat symptoms of opioid withdrawal. If loperamide toxicity is suspected, promptly discontinue the drug and start necessary therapy. For some cases of abnormal heart rhythms in which drug treatment is ineffective, electrical pacing or cardioversion may be required. Also counsel patients to take loperamide only as prescribed or according to the OTC Drug Facts label and advise patients that drug interactions with commonly used medicines may increase the risk of serious cardiac events.

We previously issued a Drug Safety Communication about this safety concern and added warnings about serious heart problems to the drug label of prescription loperamide and to the Drug Facts label of OTC loperamide products. We are continuing to evaluate this safety issue and will update the public when more information is available.

Loperamide may interact with other medicines. If you are taking other medicines, including medicines obtained without a prescription and you are unsure about taking loperamide, you should contact your doctor or pharmacist.

Overdose deaths continue to be a serious national crisis that has yet to be controlled. In 2019, nearly 50,000 people in the United States died of an opioid overdose.7 That number skyrocketed the next year with more than 81,000 drug overdose deaths in 2020, accounting for the highest number of overdose deaths ever recorded in a 12-month period.1,7 As the opioid epidemic continues to take a devastating toll on our nation and as access to prescription pain products becomes more regulated, more individuals appear to be searching for readily accessible alternatives, such as OTC loperamide.

When loperamide was introduced in 1977, the FDA initially placed it in the Schedule V list of controlled medications, basing their decision on animal data that suggested loperamide had produced opioid-like effects.11,16,17 Loperamide was later removed from the Schedule V list and became a nonprescription product by 1988 due to several volunteer studies and epidemiological data that demonstrated a low risk of physical dependence and abuse.16-19 Although safety was established through its low abuse potential, doses exceeding the recommended prescription daily dose of 16 mg demonstrated a variety of adverse effects.1,20

Throughout the past decade, a concerning number of published case reports and state poison control center calls related to loperamide misuse/abuse have been documented. Epidemiologic trends were reviewed by the National Poison Data System from January 1, 2010 to December 31, 2015, assessing the intentional misuse, abuse, and suspected suicide due to loperamide exposure.21 It found that in the span of 5 years, there was a 91% increase in loperamide exposure, with one-third of cases occurring in teens and young adults.10,21 During this study period, there were 1,736 intentional loperamide exposures.21 Overall reasons for the intentional exposure included intentional abuse (13.1%), intentional misuse (32.8%), suspected suicide (48.8%), and other (5.2%).21 These exposures increased at approximately 38 cases per year and included 15 deaths.21

There are many posts similar to this one in which users describe taking extremely large doses of loperamide to treat a variety of conditions from heroin to methadone withdrawal. Several posts even go into the pharmacology of using cimetidine or grapefruit juice to help with CYP3A4 inhibition, thus increasing plasma concentrations and the ability of loperamide to cross the BBB.23 Although not without their limitations, studies using Internet tools and online forum communities have highlighted the potential of the Internet as a resource to identify emerging drug-abuse patterns and gain valuable insight on the hard-to-reach population of illicit drug users.

The misuse of loperamide in supratherapeutic doses has been associated with a significant increase in morbidity and mortality.31 Case reports have shown CNS depression, respiratory depression, and cardiotoxicity complications, including QT prolongation, torsades de pointes (TdP), QRS prolongation, ventricular dysrhythmias, syncope, cardiac arrest, and death.11,32-34 The CNS and respiratory depression associated with loperamide overdose present similarly to overdoses typically seen with opioid analgesics, which include the hallmark characteristics of pinpoint pupils, unresponsiveness, and hypoventilation.2 Swank (2017) conducted a study that utilized the FDA Adverse Event Reporting System (FAERS) database to search for postmarketing reports of serious cardiac adverse events associated with loperamide use from 1976 to 2015.6 The researchers noted 48 cases of serious loperamideinduced cardiac adverse events, which resulted in 10 fatalities.6 In the 22 cases that were characterized as drug abuse, the median daily dose was 250 mg, with a range from 70 mg to 1,600 mg, which would involve the ingestion of 35 to 800 2-mg loperamide tablets per day.6 A majority of the cases reviewed exhibited ECG abnormalities of a widened QRS interval (up to 200 ms) and a prolonged QT interval (up to 704 ms), and all developed ventricular dysrhythmias, including monomorphic or polymorphic ventricular tachycardia (TdP).11 These cardiotoxic effects (e.g., cardiac arrest, syncope, and respiratory depression) were also prevalent in postmarketing cases for children younger than age 2 years, making it contraindicated in this patient population (TABLE 4).2

As mentioned previously, the elimination half-life of loperamide is 10.8 hours, with a range of 9.1 to 14.4 hours.2 There have been rare reports of half-lives extending to 40.9 hours with 16-mg dosages in healthy volunteers. Given the standard half-life, most poison control centers estimate 4 to 5 days before cardiac stabilization; however, one case report described a patient who remained symptomatic for 11 days postingestion with recurrent TdP and ventricular arrhythmias.39

According to the National Poison Data System, male subjects were more likely to intentionally abuse loperamide, whereas female subjects more often used it in reported suicidal attempts.21 Even though single-agent exposure is more frequent than polysubstance exposures, providers should still be mindful that both patterns contribute to increasing exposure rates. Singleagent loperamide exposures showed an increase of 24.7 exposures per year (95% CI 21.3-28.0; P

Upon diagnosis of loperamide-induced toxicity, any offending agents should be discontinued, and supportive care should be initiated.30 Selection of supportivecare treatment options is determined by individual patient factors and can include electrolyte replacement, heart rate support with isoproterenol or temporary overdrive pacing, avoidance of QT-prolonging agents, and defibrillation.30 Presentation during the early stages of ingestion can be treated similarly to other ingestions with the use of activated charcoal for patients presenting within 2 to 4 hours after ingestion.11,44,45 Activated charcoal is an adsorbent that is widely used to treat overdoses of a variety of medications and may reduce absorption in acute loperamide overdoses by up to ninefold.11,30 Activated charcoal is typically administered as a single dose, and it possesses a large surface area that allows the molecule to bind many drugs and toxins in the GI lumen, with the goal of decreasing their absorption into the systemic circulation.46 When used to treat overdoses of other toxic compounds, activated charcoal is effective within 1 hour post ingestion, but the extended administration window of 2 to 4 hours post ingestion is justified with loperamide due to its ability to reduce peristalsis.11,47

Standard advanced cardiovascular life support measures have been employed by clinicians to treat cardiac arrest and dysrhythmias secondary to loperamide overdose.24 It has been recommended that synchronized cardioversion should be performed for patients presenting with ventricular tachycardia and hemodynamic instability.24 Synchronized cardioversion involves the delivery of a low-energy shock, which is timed or synchronized to be delivered at a specific point in the QRS complex.49 For patients who are pulseless and experiencing ventricular fibrillation or ventricular tachycardia, asynchronous cardioversion (defibrillation) should be used.24 Patients experiencing TdP or polymorphic ventricular tachycardia without spontaneous resolution of their dysrhythmia should also be treated with asynchronous cardioversion.24 Once there is a perfusable rhythm established, IV magnesium should be considered.24 Amiodarone or transvenous pacing are options for patients with recurrent dysrhythmias.24 041b061a72


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