ACTION AND MECHANISM

- [ANTIDIARRHEAL], [OPIOID AGONIST (MU)]. Pethidine derivative. A µ-opioid receptor agonist that inhibits the release of acetylcholine and prostaglandins in the myenteric plexus of Auerbach, reducing intestinal peristalsis. By decreasing intestinal transit, it promotes the absorption of water and electrolytes, decreasing the frequency and volume of bowel movements, and increasing their viscosity. It also exerts a certain antisecretory effect. Furthermore, it increases anal sphincter tone, reducing incontinence.

SENIORS

Dehydration associated with diarrhea is especially common in the elderly, so there can be great variability in its effects.

PATIENT ADVICE

- It is not advisable to start treatment with an antidiarrheal without consulting a doctor, as the antidiarrheal could worsen the symptoms.

- You should see a doctor if acute diarrhea persists or worsens after two days of treatment.

- You should consult a doctor if your stools are black, oily, foul-smelling, or contain blood, mucus, or pus. You should also see a doctor if you develop a fever higher than 38°C in children or 38.5°C in adults, or if you experience abdominal pain that does not subside after a bowel movement.

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 (shigellosis), or in the case of pseudomembranous colitis caused by broad-spectrum antibiotics. In these situations, the use of loperamide is not recommended, as by inhibiting peristalsis it could increase the contact time between the intestinal mucosa and microbial toxins, thus increasing damage. In cases of bacterial diarrhea, antibiotics may sometimes be necessary.

• Situations in which inhibition of peristalsis should be avoided, such as constipation, ileus, or abdominal distension, as loperamide could worsen these conditions. If any of these symptoms appear during treatment for diarrhea, it is advisable to discontinue treatment.

PREGNANCY

FDA Pregnancy Category B. Animal studies using doses 30 times the human dose showed no evidence of fetal harm. Higher doses impaired maternal and neonatal survival. No adequate and controlled studies have been conducted in humans; therefore, this drug should only be used when safer therapeutic alternatives are unavailable.

Effects on fertility. Using doses 150-200 times higher than those used in humans, loperamide has been shown to reduce fertility in both males and females.

PHARMACOKINETICS

Oral route:

- Absorption: It is absorbed in the intestine, with a bioavailability of 40%. It undergoes first-pass metabolism. Cmax is reached at 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, resulting in inactive metabolites.

- Elimination: It is eliminated by metabolism, with metabolites excreted in the feces (30% unchanged) and in very small amounts in the urine (<2%). Its elimination half-life is approximately 10 hours. The fraction of loperamide eliminated into the intestine can be reabsorbed, resulting in enterohepatic recirculation.

Pharmacokinetics in special situations:

- Liver failure: The metabolism of loperamide may be decreased in cases of liver failure, resulting in decreased hepatic clearance.

INDICATIONS

- [DIARRHEA]. Symptomatic treatment of acute or chronic diarrheal processes.

INTERACTIONS

- Cholestyramine. A study has shown a possible inhibition of the effect of loperamide, so it is recommended to space out the administration.

- Laxatives: The administration of antidiarrheals such as loperamide with bulk-forming laxatives such as psyllium, 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 levels. Caution.

- Saquinavir: Possible reduction of saquinavir Cp with risk of decreased antiviral activity.

- Theophylline. Pharmacokinetic studies have shown a decrease in the absorption of theophylline when administered in controlled-release forms, probably due to the inhibition of intestinal motility.

LACTATION

It is unknown whether loperamide is excreted in significant amounts in breast milk, and if so, whether this could affect the infant. The American Academy of Pediatrics considers it compatible with breastfeeding, but advises caution.

CHILDREN

Safety and efficacy have not been evaluated in children under two years of age; therefore, its use is not recommended. In children over two years of age, extreme caution is advised, as there may be significant 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.

GUIDELINES FOR PROPER ADMINISTRATION

It is advisable to divide the doses of loperamide into two or three doses when administered for chronic diarrhea.

POSOLOGY

- Adults, oral:

* Acute diarrhea: An initial 4 mg will be administered, followed by 2 mg after each bowel movement.

* Chronic diarrhea: An initial dose of 4 mg will be administered, followed by 2-12 mg/24 hours until 1-2 bowel movements per day are achieved.

The maximum daily dose is 16 mg.

- Children, oral:

* Children over 5 years old:

a) Acute diarrhea: An initial 2 mg will be administered, followed by 2 mg after each bowel movement.

b) Chronic diarrhea: An initial dose of 2 mg will be administered, followed by the dose necessary to achieve 1-2 bowel movements per day.

* 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 when bowel movements are normal or there have been no bowel movements for 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 HEPATIC INSUFFICIENCY

* Specific dosage recommendations are not available. Caution is advised as first-pass metabolism may be reduced.

DOSAGE IN RENAL INSUFFICIENCY

* No dose adjustment is necessary.

PRECAUTIONS

- [HEPATIC INSUFFICIENCY]. Loperamide is eliminated via the liver, so in cases of hepatic insufficiency, first-pass metabolism may be reduced, leading to drug accumulation. Dosage adjustment may be necessary depending on the degree of insufficiency.

- [ULCERATIVE COLITIS] or [HIV INFECTION]. In patients with ulcerative colitis or AIDS, the administration of antidiarrheal drugs that inhibit intestinal motility has been associated with an increased incidence of toxic megacolon. Therefore, extreme caution is advised, and treatment should be discontinued if abdominal distension or other symptoms such as severe abdominal pain, nausea, vomiting, or loss of appetite occur.

- 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.

ADVERSE REACTIONS

The adverse effects of loperamide are generally infrequent, although moderately significant. In most cases, adverse reactions are an extension of the drug's action and primarily affect the digestive system, often being indistinguishable from the symptoms of diarrhea itself. These adverse reactions are more common with prolonged treatment. The most characteristic adverse reactions are:

- Digestive. In very rare cases (<0.01%) the appearance of [ABDOMINAL PAIN], [FLATULENCE], [DYSPEPSIA], [NAUSEA], [VOMITING], [CONSTIPATION], [DRY MOUTH], [ABDOMINAL DISTENSION], [ILEUS] or toxic [MEGACOLON]

- Neurological/psychological. Drowsiness and dizziness are rare (<0.01%). Children are especially sensitive to the nervous system effects of loperamide.

- Genitourinary. Occasionally, urinary retention may occur.

- Allergic/dermatological. These are very rare (<0.01%) [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 reported.

OVERDOSE

Symptoms: In case of overdose, central nervous system depression may occur, with stupor, drowsiness, miosis, muscle hypertonia, and respiratory depression. Urinary retention or ileal atony may also occur. This overdose is more common in cases of hepatic impairment or in young children.

Treatment: The patient should be monitored for 48 hours for possible central nervous system depression. If such symptoms appear, naloxone may be administered as an antidote. Since the duration of loperamide's effects is longer than that of naloxone, which does not exceed three hours, the naloxone administration should be repeated. Additionally, administering activated charcoal after loperamide ingestion may be advisable.

COMPOSITION

LOPERAMIDE: 2 MILLIGRAMS - HYDROCHLORIDE