What Are the Most Common Loperamide Side Effects?

Loperamide hydrochloride capsules, an antidiarrheal drug, used to control the symptoms of acute and chronic diarrhea. For ileostomy patients, it can reduce the amount and frequency of defecation, and increase the hardness of stool.

Drug Name: Loperamide hydrochloride capsules

Drug type: Occupational injury medical insurance
Use classification: Analgesics

Loperamide hydrochloride capsule ingredients

Active ingredient: Loperamide hydrochloride.
Chemical name: N, N-dimethyl-, -diphenyl-4- (p-chlorophenyl) -4-hydroxy-1-piperidine butanamide hydrochloride.
Chemical Structure:

Molecular formula: C ₂₉ H ₃₃ ClN ₂ O ₂ · HCl
Molecular weight: 513.51

Properties of Loperamide Hydrochloride Capsules

The content of this product is white or yellow-white powder.

Indications of Loperamide Hydrochloride Capsules

Antidiarrheals, used to control the symptoms of acute and chronic diarrhea.
For ileostomy patients, it can reduce the amount and frequency of defecation, and increase the hardness of stool.

Specifications of Loperamide Hydrochloride Capsules

2mg

Loperamide hydrochloride capsules dosage

This product is suitable for adults and children over 5 years.
-Acute diarrhea: The starting dose is 2 capsules for adults, 1 capsule for children over 5 years old, and 1 capsule each time afterwards.
-Chronic diarrhea: The starting dose is 2 capsules for adults and 1 capsule for children over 5 years of age. The daily dose can be adjusted to maintain normal stools 1-2 times a day. The general maintenance dose is 1 to 6 capsules per day.
-Maximum daily dose: no more than 8 capsules for adults and no more than 3 capsules per 20 kg of body weight for children.

Adverse reactions of loperamide hydrochloride capsules

Adverse reactions are mild, and allergies such as skin rash may occur. Gastrointestinal symptoms such as dry mouth, bloating, loss of appetite, gastrointestinal cramps, nausea, vomiting, and dizziness, headache, and fatigue.
Clinical trial data < br Adverse events are summarized as follows (whether or not caused by medication):
1) The incidence of adverse events in patients with acute diarrhea is more than 1.0%, and the incidence of adverse events in the loperamide hydrochloride group is at least equivalent to that in the placebo group.

Adverse events with a incidence of 1.0% or more and greater incidence in the placebo group than in the loperamide hydrochloride group included: dry mouth, flatulence, abdominal cramps, and colic.
2) The incidence of adverse events in patients with chronic diarrhea is more than 1.0%, and the incidence of adverse events in the loperamide hydrochloride group is at least equivalent to that in the placebo group.

Adverse events with a incidence of 1.0% or more and greater incidence in the placebo group than in the loperamide hydrochloride group included nausea, vomiting, headache, flatulence, abdominal pain, abdominal cramps, and colic.
3) Adverse events in 76 controlled or open studies of patients with acute and chronic diarrhea. Adverse events with an incidence of 1.0% or more in all studies are listed in the table below:

Post-marketing experience < br The following spontaneous reported adverse events are arranged in order of the body system and the reporting frequency:
Very common (> 1/10); common (> 1/100; 10); rare (> 1 / 1,000; 100); rare (> 1 / 10,000; <1 / 1,000); very rare (<1 / 10,000) Including individual reports.
The frequencies listed only reflect the reported incidence of adverse events and do not reflect actual rates as shown in clinical trials and epidemiological studies.
Abnormal skin and subcutaneous tissues < br Very rare: rash, hives and itching.
There have been reports of individual angioedema, herpes (including Stevens-Johnson syndrome), erythema polymorpha, and toxic epidermal necrosis.
Immune system abnormalities < br There are reports of individual allergic reactions, of which very few have severe allergic reactions (including anaphylactic shock) and allergic reactions.
Gastrointestinal abnormalities < br Very rare: abdominal pain, intestinal obstruction, bloating, nausea, constipation, vomiting, megacolon (including toxic megacolon), bloating and indigestion.
Renal and urinary abnormalities <br /> There are individual reports of urinary retention.
Abnormal mental system < br Very rare: drowsiness.
Nervous system abnormalities < br Very rare: loss of consciousness, reduced level of consciousness, dizziness.
Some of the adverse reactions reported in clinical studies and post-marketing experience are also common adverse reactions to diarrhea syndrome, such as abdominal pain, abdominal discomfort, nausea, vomiting, dry mouth, fatigue, drowsiness, dizziness, constipation, and bloating, which are often difficult to distinguish. Whether the response is due to diarrhea or a drug side effect.

Contraindications of Loperamide Hydrochloride Capsules

Prohibited in people who are allergic to this product.
This product should not be used as the main treatment for the following diseases:
· Acute bacterial dysentery with high fever and pus and bloody stool · Acute ulcerative colitis · Bacterial enterocolitis caused by invasive pathogens such as Salmonella, Shigella or Campylobacter · Due to the use of broad-spectrum antibiotics Pseudomembranous enteritis In general, this product should not be used when intestinal obstruction, megacolon, and toxic megacolon may be caused by inhibiting intestinal peristalsis. If constipation, bloating and intestinal obstruction occur, this product should be discontinued immediately.
This product is used for diarrhea only for symptomatic treatment. After determining the cause, specific treatment should be performed.

Precautions for loperamide hydrochloride capsules

People with diarrhea, especially children, often suffer from water and electrolyte loss. Water and electrolyte supplementation are the most important treatments.
For acute diarrhea, if you take this product for 48 hours, the clinical symptoms do not improve. This product should be discontinued and it is recommended to consult a doctor.
When AIDS patients use this product to treat diarrhea, such as the early symptoms of bloating. Treatment of this product should be stopped. There have been reports of individual AIDS patients using loperamide hydrochloride in the treatment of viral and bacterial infectious colitis and toxic colons.
Although there is no data on the pharmacokinetics of this product in patients with liver dysfunction, due to the high first-pass metabolic characteristics of this product, liver dysfunction may lead to a relative overdose of the drug. Attention should be paid to symptoms of central nervous system toxicity.
Because most of this product can be metabolized, the metabolites and the original drug are excreted through feces, so patients with kidney disease do not need to adjust the dose.
When treating this product with diarrhea, symptoms of fatigue, dizziness, or drowsiness may occur. Therefore, care should be taken when driving and operating the machine.
Keep them out of reach of children.

Loperamide hydrochloride capsules for pregnant and lactating women

Although this product has no teratogenic effect and embryo toxicity, pregnant women, especially pregnant women in the first three months of pregnancy, should still weigh the advantages and disadvantages of use.
This product can be secreted in a small amount in breast milk, so it is not suitable for lactating women.

Loperamide hydrochloride capsules for children

Patients with diarrhea, especially children, often suffer from water and electrolyte loss. Supplementing water and electrolytes is the most important treatment. Children should use this product under the guidance of a doctor.
Loperamide hydrochloride is contraindicated in infants and children under 2 years of age, and children under 5 years of age should not be treated with loperamide hydrochloride capsules.

Loperamide hydrochloride capsules for elderly

Elderly patients take the same medications as adults.

Loperamide hydrochloride capsule drug interactions

Loperamide (4 mg single dose) in combination with itraconazole (a CYP3A4 and P-glycoprotein inhibitor) can lead to a 3- to 4-fold increase in the plasma concentration of loperamide. In the same experiment, the CYP2C8 inhibitor gefibezil resulted in an approximately 2-fold increase in the plasma concentration of loperamide. Co-administration with itraconazole and gemfibrozil resulted in a 4-fold increase in loperamide plasma peaks and a 13-fold increase in total plasma exposure. Through tests of conscious activity, such as subjective lethargy and numerical symbol substitution tests, these increases are not thought to cause a CNS response.
Loperamide (single dose of 16 mg) in combination with ketoconazole (a CYP3A4 and P-glycoprotein inhibitor) can cause a 5-fold increase in the plasma concentration of loperamide. These pupil increases were not considered to result in an increase in pharmacokinetics by a pupillographic test.
The combination of loperamide with oral desmopressin can cause a three-fold increase in the plasma concentration of desmopressin, which may be caused by slow gastrointestinal motility.
The combination of drugs with similar pharmacological effects to loperamide may increase the effect of loperamide; the combination with drugs that increase gastrointestinal motility may reduce the effect of loperamide.

Loperamide hydrochloride capsules overdose

In the case of overdose (including relative overdose caused by liver dysfunction), symptoms of central nervous system depression (e.g., stiffness, coordination dysfunction, drowsiness, dilation, hypertonicity, respiratory depression), urinary retention, and bowel obstruction. Children may be more sensitive to CNS responses than adults.
If the above symptoms of overdose occur, naloxone can be used as an antidote. Because the duration of the effect of this product is longer than naloxone (1-3 hours), naloxone can be reused, and patients should be monitored for at least 48 hours to detect possible symptoms of central nervous system depression.

Pharmacology and toxicology of loperamide hydrochloride capsules

1. Pharmacology This product is an opioid receptor agonist. It stimulates mu-opioid receptors on the intestinal wall and prevents the release of acetylcholine and prostaglandins, antagonizes smooth muscle contraction, reduces intestinal motility and secretion, and prolongs the retention time of intestinal contents .
This product can increase the tension of the anal sphincter, so it can suppress fecal incontinence and urgency.
This product has a high affinity with the intestinal wall and a marked effect, so it hardly enters the systemic blood circulation.
2. Toxicology Long-term toxicology studies of loperamide for 12 months in dogs and 18 months in rats showed that the dose increased to 5 mg / kg / day (30 times the maximum human dose) and 40 mg / kg / day (240 times the maximum dosage of the human body) showed some decrease in weight gain and increase in food consumption, and no other side effects were found. The results show that the non-toxic dose levels (NTEL) for dogs and rats are 1.25 mg / kg / day (8 times the maximum human dose) and 10 mg / kg / day (60 times the maximum human dose). The results of special toxicological studies in vivo and in vitro show that loperamide is non-genotoxic and non-carcinogenic. In rats, high-dose loperamide (40 mg / kg / day-240 times the maximum human dose) can affect fertility and fetal survival. At low doses, loperamide does not affect the health of the mother and fetus, nor does it affect the development of the pups during and after delivery.
The toxic effects appearing in the above preclinical toxicology studies can only be observed when the dosage exceeds the human dosage many times and is used for a long time, and it is not found in the range of the dosage course of clinical medication.

Pharmacokinetics of loperamide hydrochloride capsules

Absorption: Most of the loperamide is absorbed by the intestinal wall, but the bioavailability is only about 0.3% due to the obvious first pass effect. The different dosage forms of loperamide hydrochloride (hard umbilical capsules, soft capsules, tablets with or without coating, chewable tablets, orally disintegrating tablets, oral liquid) are bioequivalent in the speed and extent of absorption.
Distribution: The distribution in the study showed that it has high affinity to the intestinal wall and easily binds to receptors in the longitudinal muscle layer. The binding rate of loperamide to plasma proteins (mainly albumin) was 95%. Preclinical data show that loperamide is a P-glycoprotein substrate.
Metabolism: Loperamide is almost exclusively taken up by the liver, metabolized, bound and excreted by bile. The main metabolic pathway of loperamide is through oxidized N-desmethylation, and it is mainly regulated by cytochrome oxidases CYP3A4 and CYP2C8. Due to the very strong first-pass effect, the drug prototype concentration in plasma is very low.
Excretion: The elimination half-life of loperamide in the human body is 11 (9-14) hours. Drug prototypes and metabolites are excreted mainly through feces.
Pediatric population: Pharmacokinetic studies have not been conducted in pediatric populations. Children and adults are expected to have similar pharmacokinetic characteristics and similar drug interaction characteristics.

Storage of loperamide hydrochloride capsules

Sealed and stored in a dry place.

Loperamide hydrochloride capsule packaging

Packed in aluminum-plastic blister board; 6 tablets / board / box, 20 tablets / board / box.

Expiry date of loperamide hydrochloride capsules

60 months.

Executive standard of loperamide hydrochloride capsules

National Bureau of Drug Standards YBH04562010

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