Action and mechanism- [ANTIDIARRHEAL], [OPIOID AGONIST (MU)]. Pethidine derivative. A µ-opiate receptor agonist that inhibits the release of acetylcholine and prostaglandins in Auerbach's myenteric plexus, reducing intestinal peristalsis. By decreasing intestinal transit, it promotes the absorption of water and electrolytes, decreasing the frequency and quantity of bowel movements, and increasing their viscosity. It also exerts a certain antisecretory effect. It also increases the tone of the anal sphincter, decreasing incontinence.PharmacokineticsOral route:- Absorption: It is absorbed in the intestine, presenting a bioavailability of 40%. It undergoes first-pass metabolism. Cmax is reached after 5 hours (capsules) or 2.5 hours (solutions). Its effects last up to 24 hours.- Distribution: It circulates bound to plasma proteins (97%). It crosses the blood-brain barrier with great difficulty.- Metabolism: It is metabolized in the liver, giving rise to inactive metabolites.- Elimination: It is eliminated by metabolism, with the metabolites excreted in the feces (30% unchanged) and in very small quantities in the urine (<2%). Its elimination half-life is approximately 10 hours. The fraction of loperamide eliminated in the intestine can be reabsorbed, giving rise to an enterohepatic cycle.Pharmacokinetics in special situations:- Liver failure: The metabolism of loperamide may be decreased in cases of liver failure, leading to a decrease in hepatic clearance.Indications- [DIARRHEA]. Symptomatic treatment of acute or chronic diarrheal processes. Dosage- Adults, oral:* Acute diarrhea: 4 mg will be administered initially, followed by 2 mg after each bowel movement.* Chronic diarrhea: 4 mg will be administered initially, followed by 2-12 mg/24 hours until 1-2 bowel movements are achieved daily. The maximum daily dose is 16 mg.- Children, oral:* Children over 5 years:a) Acute diarrhea: 2 mg will be administered initially, followed by 2 mg after each bowel movement.b) Chronic diarrhea: 2 mg will be administered initially, and then the dose necessary to achieve 1-2 bowel movements daily.* Children 2-5 years: Initially 0.4 ml/kg/24 hours, up to a maximum of 1.2 ml/kg/24 hours. Treatment should be discontinued as soon as bowel movements are normal or have not occurred within 12 hours.* Children under 2 years of age: The safety and efficacy of loperamide in children under 2 years of age have not been evaluated. The maximum daily dose is 6 mg/20 kg. Dosage in renal impairment* No dose adjustment is necessary. Dosage IN LIVER INFECTION * No specific dosage recommendations are available. Caution is advised as its first-pass metabolism may be decreased.Rules for correct administrationIt is advisable to divide the dose of loperamide into two or three doses when administered for chronic diarrhea.Contraindications- [OPIOID ALLERGY] or to any component of the medication.- Bloody diarrhea caused by invasive microorganisms such as enteroinvasive strains of Escherichia coli, Salmonella ([SALMONELLOSIS]) or Shigella ([SHIGELOSIS]), or in the case of [PSEUDOMEMBRANOUS COLITIS], caused by broad-spectrum antibiotics. In these situations, the use of loperamide is not recommended, since inhibiting peristalsis could increase the contact time between the intestinal mucosa and microbial toxins, increasing the damage. In cases of bacterial diarrhea, it may sometimes be necessary to administer antibiotics. Situations in which inhibition of peristalsis is to be avoided, such as [CONSTIPATION], [ILEUS] or [ABDOMINAL DISTENSION], since loperamide may aggravate the process. If any of these symptoms appear during the treatment of diarrhea, it is advisable to discontinue treatment. Warnings about excipients: - This medicine contains lactose. Patients with hereditary [LACTOSE INTOLERANCE] or galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. Precautions - [LIVER FAILURE]. Loperamide is eliminated by the liver, so in cases of failure, first-pass metabolism may be reduced, with consequent accumulation of the medicine. It may be necessary to readjust the dosage depending on the degree of failure. - [ULCERATIVE COLITIS] or [HIV INFECTION]. In patients with ulcerative colitis or AIDS, the administration of antidiarrheals that inhibit intestinal motility has been associated with an increased incidence of toxic megacolon, so extreme caution is advised and treatment is discontinued if abdominal distension or other symptoms such as severe abdominal pain, nausea, vomiting, or loss of appetite appear. - Dehydration. Inhibition of intestinal peristalsis can lead to fluid retention in the intestinal lumen, worsening dehydration. It is advisable to first correct the patient's dehydration by administering water or oral rehydration solutions. Patient advice - It is not advisable to start treatment with an antidiarrheal without consulting a doctor, as the antidiarrheal could worsen symptoms. - Consult a doctor if acute diarrhea persists or worsens after two days of treatment. - Consult a doctor if stools are black, oily, foul-smelling, or if there is any evidence of blood, mucus, or pus. You should also consult a doctor if a fever above 38ºC appears in children or 38.5ºC in adults, or if the patient experiences abdominal pain that does not decrease with bowel movements.Interactions- Cholestyramine. A possible inhibition of the effect of loperamide has been recorded in a study, so it is recommended to space out the administration.- Laxatives: The administration of antidiarrheals such as loperamide with laxatives that increase intestinal bolus such as ispaghula, methylcellulose, agar or sterculia gum is not recommended, because simultaneous use may cause intestinal obstructions with serious consequences for patients.- Ritonavir: possible increase in loperamide Cp. Caution.- Saquinavir: Possible reduction in saquinavir Cp with a risk of decreased antiviral activity. - Theophylline. Pharmacokinetic studies have shown a decrease in theophylline absorption when administered in controlled-release forms, probably due to inhibition of intestinal motility. Pregnancy: FDA Category B. Animal studies using doses 30 times the human dose showed no evidence of fetal harm. Higher doses altered maternal and neonatal survival. Adequate, controlled studies have not been conducted in humans; therefore, the use of this drug is only accepted in the absence of safer therapeutic alternatives. Effects on Fertility: Using doses 150-200 times the human dose, loperamide has been shown to reduce fertility in males and females. Breast-Feeding: It is unknown whether loperamide is excreted in significant amounts in breast milk, and whether this could affect the infant. The American Academy of Pediatrics considers it compatible with breastfeeding, but extreme caution is advised. Children Safety and efficacy have not been evaluated in children under two years of age, so its use is not recommended. In children over two years of age, extreme caution is advised, as there may be great variability in the pharmacological response due to dehydration. Similarly, children under three years of age are more sensitive to the central opioid effects of loperamide. Elderly Dehydration associated with diarrhea is especially common in the elderly, so there may be great variability in its effects. Adverse Reactions The adverse effects of loperamide are generally infrequent, although moderately significant. In most cases, adverse reactions are an extension of the pharmacological action and primarily affect the digestive system. In most cases, they are indistinguishable from the symptoms of diarrhea itself. These adverse reactions are more common with prolonged treatment. The most characteristic adverse reactions are: - Digestive. Very rarely (<0.01%) the appearance of [ABDOMINAL PAIN], [FLATULENCE], [DYSPEPSIA], [NAUSEA], [VOMITING], [CONSTIPATION], [DRY MOUTH], [ABDOMINAL DISTENSION], [ILEUS] or [MEGACOLON] toxic- Neurological/psychological. The presence of [DROWSY] and [DIZZINESS] is rare (<0.01%). Children are especially sensitive to the nervous effects of loperamide.- Genitourinary. Occasionally [URINARY RETENTION] may appear.- Allergic/dermatological. Very rare (<0.01%) are [EXANTHEMATOUS ERUPTIONS], [URTICARIA] or [PRURITUS]. Isolated cases of [ANGIOEDEMA], [STEVENS-JOHNSON SYNDROME], [ERYTHEMA MULTIFORME], and [TOXIC EPIDERMAL NECROLYSIS] have been reported, although their relationship with loperamide has not been evaluated. Isolated cases of [HYPERSENSITIVITY REACTIONS], including [ANAPHYLAXIS,] have also been described. Overdose Symptoms: In the event of an overdose, central nervous system depression may occur, with stupor, drowsiness, miosis, muscular hypertonia, and respiratory depression. Urinary retention or ileal atony may also occur. This overdose occurs primarily in cases of liver failure or in young children. Treatment: The patient should be monitored for 48 hours to detect possible central nervous system depression. If these symptoms appear, naloxone may be administered as an antidote. Since loperamide's effects last longer than naloxone's, which lasts no more than three hours, naloxone should be administered repeatedly. It may also be advisable to administer activated charcoal after taking loperamide.