Loperamide is a synthetic agent chemically related to the opiates with anti-diarrheal properties. Loperamide decreases gastrointestinal motility by effects on the circular and longitudinal muscles of the intestine. Part of its anti-diarrheal effect may be due to a reduction of gastrointestinal secretion produced by opioid receptor binding in the intestinal mucosa.
One of the long-acting synthetic ANTIDIARRHEALS; it is not significantly absorbed from the gut, and has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally.
Loperamide is a medication used to decrease the frequency of diarrhea. It is often used for this purpose in gastroenteritis, inflammatory bowel disease, and short bowel syndrome. It is not recommended for those with blood in the stool. The medication is taken by mouth
Mechanism of Action of Loperamide
Loperamide interferes with peristalsis by a direct action on the circular and longitudinal muscles of the intestinal wall to slow motility. Loperamide also may directly inhibit fluid and electrolyte secretion and/or increase water absorption. By increasing the transit time of the intestinal contents, loperamide reduces fecal volume, increases the bulk density and the viscosity of the feces, and decreases the loss of electrolytes and fluids from the body. Although loperamide is chemically related to opioids, it does not exhibit analgesic or opiate-like effects, even at high doses. Tolerance to the antidiarrheal effect of loperamide has not been observed, and it does not appear to produce physical dependence.
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The present study investigates the mechanism of the central analgesic effect of loperamide. Adult male Sprague-Dawley rats were subjected to surgery for catheter placement. Following baseline testing, different groups of rats were administered fixed intrathecal doses (1 ug, 3 ugs, 10 ug, and 30 ugs) of loperamide and morphine. Analgesia was compared employing Hargreaves paw withdrawal apparatus at 15 min, 30 min, 60 min, 90 min, and 120 min. Additionally, CTOP, a specific mu-opioid receptor antagonist was co-administered with loperamide to examine the mu-opioid receptor-mediated loperamide analgesia. Furthermore, nefiracetam, a calcium channel opener, was co-administered with loperamide or morphine to evaluate the involvement of Ca(2+) channels in loperamide showed an analgesic effect which was comparable to morphine. However, loperamide produced longer analgesia and the analgesic effect was significantly better at 42 hr and 49 hr compared to morphine. CTOP completely reversed loperamide analgesia. Though nefiracetam significantly reversed loperamide analgesia, it did not have any effect on morphine-induced analgesia. Our findings suggest that loperamide administered intrathecally produces analgesia which is mediated through the mu-opioid receptor and subsequent blockade of downstream calcium channels.
Indications of Loperamide
- Traveler’s Diarrhea
- Diarrhea, Chronic
- Diarrhea, Acute
- Lymphocytic Colitis
- Diarrhea
- Gastroenteritis,
- Inflammatory bowel disease,
- Short bowel syndrome.
- For the control and symptomatic relief of acute nonspecific diarrhea and of chronic diarrhea associated with inflammatory bowel disease or gastroenteritis. Also used for reducing the volume of discharge from ileostomies.
Therapeutic Indications of Loperamide
- Antidiarrheals
- Loperamide is used in the control and symptomatic relief of acute nonspecific diarrhea and of chronic diarrhea associated with inflammatory bowel disease.
- The fixed combination containing loperamide and simethicone is used for the control and symptomatic relief of diarrhea when relief of flatulence, bloating, and gas pain also is indicated.
- Loperamide has also been effective in controlling chronic functional (idiopathic) diarrhea and chronic diarrhea caused by bowel resection or organic lesions.
- Many physicians are resistant to the idea of prescribing loperamide for acute infectious traveler’s diarrhea and community-acquired diarrhea because of the fear of possible adverse effects.
- Large randomized trials with loperamide, either alone or as an adjunct to antibiotic treatment, have in fact revealed positive rather than negative effects. International guidelines now often support the use of loperamide for the treatment of infectious diarrhea without dysentery.
- There seems to be no reason to systematically avoid loperamide in patients with dysentery, but caution is advised.
- Loperamide can be used as monotherapy or as an adjunct to antibiotic treatment in immunocompetent adults with acute infectious traveler’s diarrhea or community-acquired diarrhea without severe comorbidities. This can reduce both the frequency of diarrhea and the time until diarrhea stops without the risk of severe complications.
Contra-Indications of Loperamide
- Loperamide HCl is contraindicated in patients with a known hypersensitivity to loperamide hydrochloride or to any of the excipients.
- Loperamide HCl is contraindicated in patients with abdominal pain in the absence of diarrhea.
- Loperamide HCl is not recommended in infants below 24 months of age.
- Loperamide HCl should not be used as the primary therapy – In patients with acute dysentery, which is characterized by blood in stools and high fever, in patients with acute ulcerative colitis,in patients with bacterial enterocolitis caused by invasive organisms including Salmonella, Shigella, and Campylobacter,in patients with pseudomembranous colitis associated with the use of broad-spectrum antibiotics.
Dosage of Loperamide
Strengths: 2 mg; 1 mg/5 mL; 1 mg/7.5 mL
Diarrhea
Tablets, capsules, and liquid
- Initial: 4 mg orally after the first loose stool, then
- Maintenance: 2 mg after each loose stool, not to exceed 16 mg in any 24-hour period. Clinical improvement is usually observed within 48 hours.
Chewable tablets
- Initial: 4 mg after the first loose stool, then
- Maintenance: 2 mg after each subsequent loose stool, but not exceeding 8 mg in 24 hours.
Diarrhea, Chronic
Tablets, capsules, and liquid
- Initial: 4 mg orally once followed by 2 mg orally after each loose stool, not to exceed 16 mg in any 24-hour period.
- Maintenance: The average daily maintenance dosage is 4 to 8 mg. Clinical improvement is usually observed within 10 days. If clinical improvement is not observed at a maximum dosage of 16 mg for a duration of 10 days, symptoms are unlikely to be controlled by further administration.
Pediatric Diarrhea, Acute
2 to 6 years (13 to 20 kg)
- Liquid formulation only to be used in this age group.
- Initial: 1 mg orally 3 times a day for the first day, then
- Maintenance: 0.1 mg/kg/dose after each loose stool, but not exceeding the initial dose.
6 to 8 years (20 to 30 kg) Tablets, capsules, and liquid
- Initial: 2 mg orally twice a day for the first day, then
- Maintenance: 0.1 mg/kg/dose after each loose stool, but not exceeding the initial dose.
Chewable tablets
- Initial: 2 mg orally after the first loose stool, then
- Maintenance: 1 mg orally after each subsequent loose stool, but not exceeding 4 mg in 24 hours.
8 to 12 years (greater than 30 kg) Tablets, capsules, and liquid
- Initial: 2 mg orally 3 times a day for the first day, then
- Maintenance: 0.1 mg/kg/dose after each loose stool, but not exceeding initial dose.
Chewable tablets
- Initial: 2 mg orally after the first loose stool, then
- Maintenance: 1 mg orally after each subsequent loose stool, but not exceeding 6 mg in 24 hours.
12 to 18 years
- Tablets, chewable tablets, capsules, and liquid:
- Initial: 4 mg after the first loose stool, then
- Maintenance: 2 mg after each subsequent loose stool, but not exceeding 8 mg in 24 hours.
Pediatric Diarrhea, Chronic
less than 2 years
- The therapeutic dose for the treatment of chronic diarrhea has not been established for this patient population.
Side Effects of Loperamide
The most common side effects
- Abdominal or stomach cramps
- dizziness or lightheadedness
- heartburn
- Stomach pain, especially if it comes along with fever and diarrhea or constipation
- Yellowing of the skin or eyes
- Loss of appetite
- Constipation
- Chest pain or discomfort
- lightheadedness, dizziness, or fainting
- unusual tiredness or weakness
- fast, pounding, or irregular heartbeat or pulse
- increased watering of mouth
- lightheadedness
- constipation;
- vision changes;
- breast swelling (in men or women); or
- decreased sex drive, impotence, or difficulty having an orgasm.
- blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
- restless muscle movements in your eyes, tongue, jaw, or neck;
Common
- Drowsiness and lightheadedness the day after taking the medicine.
- Confusion.
- Numbed emotions.
- Visual disturbances such as blurred vision or double vision.
- Shaky movements and unsteady walk (ataxia).
- Muscle weakness.
- Dizziness.
- Headache.
- Skin rashes.
- Disturbances of the gut such as diarrhoea, constipation, nausea, vomiting or abdominal pain.
- Changes in sex drive.
- Low blood pressure (hypotension).
- Blood disorders.
- Unexpected aggression, restlessness or irritability.
- Nightmares or hallucinations
Rare
- agitation
- anxiety
- behavioral changes, including aggressiveness, angry outbursts,
- confusion
- increased trouble sleeping
- muscle spasms
- shortness of breath
- difficult or labored breathing
- difficulty with swallowing
- dizziness, faintness, or lightheadedness
- frequent urination
- hallucinations
- bloating or swelling of the face, arms, hands, lower legs, or feet
- blurred vision
- hives or welts, itching, or skin rash
- the increased volume of pale, dilute urine
Drug Interactions of Loperamide
Loperamide may interact with following drugs, supplements, & may change the efficacy of drugs
- barbiturates (e.g., phenobarbital, butalbital)
- benzodiazepines (e.g., diazepam, lorazepam)
- phenothiazines (e.g., perphenazine, fluphenazine)
- quinidine
- ritonavir
- tricyclic antidepressants (e.g., amitriptyline, nortriptyline)
Pregnancy & Lactation of Loperamide
FDA Pregnancy Category C
Pregnancy
Teratology studies have been performed in rats using oral doses of 2.5, 10, and 40 mg/kg/day, and in rabbits using oral doses of 5, 20, and 40 mg/kg/day. These studies have revealed no evidence of impaired fertility or harm to the fetus at doses up to 10 mg/kg/day in rats (5 times the human dose based on body surface area comparison) and 40 mg/kg/day in rabbits.
While manufacturers do not recommend loperamide use during lactation; the American Academy of Pediatrics generally considers the use of loperamide compatible with breastfeeding as use during lactation is unlikely to adversely affect the infant. Small amounts of loperamide may appear in human breast milk, based on data of the excretion of loperamide in human breast milk at low levels following the use of a prodrug, loperamide oxide. As with all medications, women should consult their healthcare professional prior to self-treatment during lactation.
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