DIARYL

Loperamide is an anti-diarrheal agent that is available as an over-the-counter product for treating diarrhea.

The drug was first synthesized in and used medically in 1976.

It is a highly lipophilic synthetic phenylpiperidine opioid that works by binding to mu-opioid receptors on intestinal muscles to decrease intestinal motility and electrolyte loss.

Loperamide has a chemical structure that is similar to diphenoxylate and haloperidol; 2 however, loperamide works on mu (μ)-opioid receptors to mediate its pharmacological actions.

Loperamide is indicated for the relief of diarrhea, including Travelers'Diarrhea.

As an off-label use, it is often used to manage chemotherapy-related diarrhea.

Loperamide is an anti-diarrheal agent that provides symptomatic relief of diarrhea.

It decreases peristalsis and fluid secretion in the gastrointestinal tract, delays colonic transit time, and increases the absorption of fluids and electrolytes from the gastrointestinal tract. 2, 1, 5 Loperamide also increases rectal tone, 1 reduces daily fecal volume, and increases the viscosity and bulk density of feces.

It also increases the tone of the anal sphincter, thereby reducing incontinence and urgency. 3, 8 The onset of action is about one hour and the duration of action can be up to three days.

While loperamide is a potent mu-opioid receptor agonist, 3 it does not mediate significant analgesic activity at therapeutic and supratherapeutic doses. 2, 3 However, at high doses of loperamide, inhibition of P-glycoprotein-mediated drug efflux may allow loperamide to cross the blood-brain barrier, where loperamide can exert central opioid effects and toxicity.

At very high plasma concentrations, loperamide can interfere with cardiac conduction.

Because loperamide inhibits the

Na + -gated cardiac channels and ether-a-go-go–related gene potassium channels, 4 the drug can prolong the QRS complex and the QTc interval, which can lead to ventricular dysrhythmias, monomorphic and polymorphic ventricular tachycardia, torsade de pointes, ventricular fibrillation, Brugada syndrome, cardiac arrest, and death.

Loperamide is well absorbed from the gastrointestinal tract; however, it undergoes extensive first-pass metabolism to form metabolites that are excreted in the bile.

Therefore, little loperamide actually reaches the systemic circulation.

The drug bioavailability is less than 1%.

Following oral administration of a 2 mg capsule of loperamide, plasma concentrations of unchanged drug were below 2 ng/mL.

Plasma loperamide concentrations are highest approximately five hours after administration of an oral capsule of loperamide and 2.5 hours after the liquid formulation of the drug.

Loperamide has a large volume of distribution.

Although highly lipophilic, loperamide does not cross the blood-brain barrier and generally acts peripherally.

Loperamide is extensively metabolized.

The primary metabolic pathway is oxidative N-demethylation mediated by CYP2C8 and CYP3A4, to form N-demethyl loperamide.

CYP2B6 and CYP2D6 play a minor role in loperamide N-demethylation.

Metabolites of loperamide are pharmacologically inactive.

Hover over products below to view reaction partners Loperamide N-Desmethyloperamide Loperamide-N-oxide Loperamide carbinolamide metabolite.

Loperamide and its metabolites in the systemic circulation undergo biliary excretion.

Excretion of the unchanged loperamide and its metabolites mainly occurs through the feces.

Only 1% of an absorbed dose excreted unchanged in the urine.

The apparent elimination half-life of loperamide is 10.8 hours with a range of 9.1-14.4 hours.

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LD50 is 185 mg/kg in rats.

Due to its actions on opioid receptors, loperamide has been misused and abused to self-manage opioid withdrawal symptoms and to induce euphoria. 1, 4 However, loperamide is associated with a risk of experiencing a range of adverse effects, often life-threatening, if taken for non-therapeutic reasons or at doses higher than the recommended dose.

Loperamide overdose can lead to a range of cardiac and non-cardiac effects.

Chronic ingestion of doses ranging from 70 mg to 1600 mg daily.

• which is four to 100 times the recommended dose.

• 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.

These cases included instances of loperamide misuse and abuse.

In case of cardiac effects, it is recommended that loperamide is discontinued and therapies to manage and prevent cardiac arrhythmias are initiated.

Cases of loperamide overdose may cause opioid toxic effects including CNS depression (e.g. altered mental status, stupor, coordination disorders, somnolence, miosis, muscular hypertonia, respiratory depression), hypotension, urinary retention, and paralytic ileus.

Naloxone may reverse the opioid-related toxicity, including CNS and respiratory depression, and hypotension, associated with loperamide overdosage.

Allergy alert

Do not use if you have ever had a rash or other allergic reaction to loperamide HCl Heart alert: Taking more than directed can cause serious heart problems or death Do not use if you have bloody or black stool Ask a doctor before use if you have.

• mucus in the stool.

• a history of liver disease.

• a history of abnormal heart rhythm Ask a doctor or pharmacist before use if you are taking a prescription drug.

Loperamide may interact with certain prescription drugs.

When using this product tiredness, drowsiness or dizziness may occur.

Be careful when driving or operating machinery.

Stop use and ask a doctor if.

• symptoms get worse.

• diarrhea lasts for more than 2 days.

• you get abdominal swelling or bulging.

These may be signs of a serious condition.

If pregnant or breast-feeding, ask a health professional before use.

Keep out of reach of children.

In case of overdose, get medical help or contact a Poison Control Center right away.

• drink plenty of clear fluids to help prevent dehydration caused by diarrhea.

• find right dose on chart.

If possible, use weight to dose; otherwise use age.

• shake well before using.

• use only enclosed dosing cup specifically designed for use with this product.

Do not use any other dosing device.

• mL = milliliter adults and children 12 years and over 30 mL after the first loose stool; 15 mL after each subsequent loose stool; but no more than 60 mL in 24 hours children 9-11 years (60-95 lbs) 15 mL after the first loose stool; 7.5 mL after each subsequent loose stool; but no more than 45 mL in 24 hours children 6-8 years (48-59 lbs) 15 mL after the first loose stool; 7.5 mL after each subsequent loose stool; but no more than 30 mL in 24 hours children 2-5 years (34 to 47 lbs) ask a doctor children under 2 years (up to 33 lbs) do not use.

Other information.

• each 30 mL contains: sodium 15 mg.

• store between 20-25 ° C (68-77 ° F).