Diphenoxylate

Diphenoxylate is an Opiate receptor agonist belonging to Antidiarrheal.

Diphenoxylate is an antidiarrheal medication used with atropine to manage diarrhea.

Diphenoxylate is well absorbed from GI tract with 90% absorption. May get distributed in breast milk. It has protein binding of 74-95%. It is rapidly and extensively metabolized in liver and is excreted mainly as metabolites and their conjugates in the feces.

Diphenoxylate shows side effects like Nausea, vomiting, loss of appetite, headache, restlessness, tiredness, confusion, changes in mood, stomach discomfort, Drowsiness or sleepiness, Skin rash.

Diphenoxylate is available in the form of Oral tablets.

Diphenoxylate is available in India, US, China, France, Italy, and Australia.

Diphenoxylate belongs to the Antidiarrheal agent acts as an Opiate receptor agonist.

Diphenoxylate is an opiate receptor agonist that stimulate mu receptors in GI tract to decrease the peristalsis and constrict the sphincters. Diphenoxylate has a direct effect on circular smooth muscle of the bowel, that conceivably results in segmentation and prolongation of gastrointestinal transit time. The clinical antidiarrheal action of diphenoxylate may thus be a consequence of enhanced segmentation that allows increased contact of the intraluminal contents with the intestinal mucosa.

The Onset of action of Diphenoxylate is 45min -1 hour.

The Duration of action of Diphenoxylate is 3-4 hours.

Diphenoxylate is used for the management of diarrhea along with other treatments. This medicine is not recommended for use in children below 2 years of age.

Diphenoxylate is approved for use in the following clinical indications

• Acute and chronic diarrhea

Diphenoxylate is an antidiarrheal medication used with atropine to manage diarrhea.

• Acute diarrhea

Adult: Initial dose: 10 mg, followed by 5 mg every 6 hours.

Child:

>12 years: 5 mg three times a day.

9-12 years: 2.5 mg 4 times daily

4-8 years: 2.5 mg three times a day.

• Chronic diarrhea

Adult: Initial dose: 10 mg followed by 5 mg every 6 hours. Discontinue use if no clinical improvement is noted after 10 days of continuous usage at 20 mg/day. Max: 20 mg/day.

Diphenoxylate is contraindicated in patients with

• Infants and children <4 years

Jaundice, intestinal obstruction.

Diarrhea is associated with pseudomembranous colitis or enterotoxin-producing bacteria.

• Infectious diarrhea

This medicine is not recommended for use in patients having infectious diarrhea. The symptoms may worsen and get prolonged if this medicine is used in such cases. Any incidence of diarrhea accompanied by the presence of blood or pus in stools and high fever should be promptly reported to the doctor.

• Driving or operating machinery

The use of this medicine may cause symptoms such as dizziness, drowsiness, etc. in some patients. It is advised that you do not perform any activities such as driving a vehicle or operating machinery if you experience any of these symptoms.

• Use in children

This medicine is not recommended for use in patients less than 2 years of age since the safety and efficacy of use are not clinically established.

• Liver diseases

This medicine should be used with caution in patients suffering from liver diseases due to the increased risk of adverse effects. Close monitoring of liver function tests is necessary while receiving this medicine. Appropriate dose adjustments or replacement with a suitable alternative may be required in some cases based on the clinical condition.

• Kidney diseases

This medicine should be used with caution in patients suffering from kidney diseases due to the increased risk of severe adverse effects. Close monitoring of kidney function tests is necessary while receiving this medicine. Appropriate dose adjustments or replacement with a suitable alternative may be required in some cases based on the clinical condition.

Consumption of alcohol during treatment with this medicine may increase the risk of severe side effects. These side effects may include confusion, dizziness, nausea, vomiting, weakness, and fainting.

This medicine is not recommended for use in breastfeeding women unless necessary. The risks and benefits should be discussed with the doctor before taking this medicine.

This medicine is not recommended for use in pregnant women unless necessary. The risks and benefits should be discussed with the doctor before taking this medicine.

Common

● GI effects, Headache, Drowsiness, Dizziness, Restlessness, Euphoria, Depression, Numbness of the extremities; Hypersensitivity reactions, Swelling of the gums.

The common side effects of Diphenoxylate include the following

Common side effects

• Nausea, Vomiting, Loss of appetite, Headache, Restlessness, Tiredness, Confusion, Changes in mood, Stomach discomfort, Drowsiness or Sleepiness, and Skin rash.

Rare side effects

● Numbness in arms and legs, ongoing pain that begins in the stomach area but may spread to the back, Stomach bloating, Shortness of breath, Hives, Rash, Itching, Swelling of the Eyes, Face, Tongue, Lips, Gums, Mouth, Hands, Feet, Ankles, or Lower legs, Difficulty swallowing or breathing, Hoarseness.

• Pregnancy

Pregnancy category

Diphenoxylate is not recommended for use in pregnant women unless necessary. The risks and benefits should be discussed with the doctor before taking Diphenoxylate.

• Nursing Mothers

Diphenoxylate is not recommended for use in breastfeeding women unless necessary. The risks and benefits should be discussed with the doctor before taking Diphenoxylate.

• Pediatric Use

Diphenoxylate is not recommended for use in patients less than 2 years of age since the safety and efficacy of use are not clinically established.

Symptoms: Atropinism may persist for 2-3 hr (e.g. high fever, generalized flushing, and tachypnoea). Drowsiness, Miosis, Hypotonia, Loss of tendon reflexes, Nystagmus, and Seizures followed by respiratory depression and total apnoea may manifest 12-30 hr after drug ingestion.

Treatment: Empty stomach by emesis or by gastric lavage. Gastric lavage may be effective even after several hr due to decreased GI motility and pylorospasm. Treatment is supportive and symptomatic and monitored closely for 48 hr. Naloxone may be useful in the treatment of severe respiratory depression.

Pharmacodynamic

Diphenoxylate, an antidiarrheal, is effective as adjunctive therapy in the management of diarrhea. Diphenoxylate is rapidly and extensively metabolized in man by ester hydrolysis to diphenoxylic acid (difenoxine), which is biologically active and the major metabolite in the blood.

Pharmacokinetics

• Absorption

Diphenoxylate is well absorbed from the GI tract with 90% absorption.

• Distribution

May get distributed in breast milk. It has protein binding of 74-95%.

• Metabolism and Excretion

It is rapidly and extensively metabolized in the liver and is excreted mainly as metabolites and their conjugates in the feces.

• https://www.mims.com/india/drug/info/diphenoxylate?type=full&mtype=generic
• https://medlineplus.gov/druginfo/meds/a601045.html
• https://go.drugbank.com/drugs/DB01081
• https://www.practo.com/medicine-info/diphenoxylate-2995-api