loperamide (OTC)

Frequency Not Defined

Dizziness

Fatigue

Abdominal pain

Constipation

Nausea

Dry mouth

Angioedema

Bullous eruptions

Flatulence

Rash

Postmarketing Reports

Pancreatitis

QT/QTc interval prolongation, Torsades de Pointes, other ventricular arrhythmias, cardiac arrest, syncope, and death

Contraindications

Hypersensitivity, bloody diarrhea, high fever, infectious diarrhea, pseudomembranous colitis

Patients in whom constipation must be avoided

Abdominal pain without diarrhea

Avoid use as primary therapy with acute dysentery (bloody stools and high fever, acute ulcerative colitis, bacterial enterocolitis [caused by Salmonella, Shigella, and Campylobacter), pseudomembranous colitis associated with antibiotic use)

Age <2 years

Cautions

May cause drowsiness or dizziness, which may impair physical abilities to operate heavy machinery or tasks requiring mental alertness

Hypersensitivity reactions reported, including anaphylaxis, rash, urticaria, and rare cases of Steven’s Johnson syndrome or toxic epidermal necrolysis

Discontinue if no improvement seen within 48 hours in patients with acute diarrhea, symptoms worsen, or abdominal swelling or bulging develops

Discontinue promptly if constipation, abdominal pain or distention, blood in stool, or ileus develops; do not use when peristalsis inhibition should be avoided (ie, due to potential for ileus, megacolon, or toxic megacolon)

Discontinue therapy if symptoms of abdominal distention occur in patients with AIDS; cases of toxic megacolon reported with infectious colitis, resulting from viral or bacterial pathogens

Use with caution in patients with hepatic impairment due to reduced first pass metabolism; monitor for signs of CNS toxicity

Use of higher than recommended doses or abuse of loperamide 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

Dehydration, particularly in pediatric patients less than 6 years of age, may further influence variability of response to loperamide

Avoid loperamide in combination with drugs or herbal products known to prolong QT interval, including Class 1A (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmics, antipsychotics (e.g., chlorpromazine, haloperidol, thioridazine, ziprasidone), antibiotics (e.g., moxifloxacin), or any other drug known to prolong the QT interval (e.g., pentamidine, methadone)

Avoid administering therapy to patients with risk factors for QT prolongation, including patients with congenital long QT syndrome, with a history of cardiac arrhythmias or other cardiac conditions, elderly patients and those with electrolyte abnormalities

Patients with a history of abnormal heart rhythm or liver disease, should ask their healthcare provider before using the product; taking more than directed can cause serious heart problems or death

Potential toxic dose in patients <6 years: 0.4 mg/kg  

Pregnancy category: B

Lactation: Not known if distributed in breast milk; use caution

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Slows intestinal motility through opioid receptor; has direct effects on circular and longitudinal muscle; reduces fecal volume; increases viscosity

Absorption

Bioavailability: 0.3%

Onset: 1-3 hr

Duration: 41 hr

Peak plasma time: 5 hr (capsule); 2.5 hr (liquid)

Distribution

Poor penetration through blood-brain barrier

Metabolism

Significant first-pass metabolism, resulting in very low plasma level of drug

Metabolites: Glucuronide (inactive)

Elimination

Elimination half-life: 7-14 hr

Excretion: Feces (30-40%), urine (1%)