Diphenoxylate/ Atropine

Registered South African indications:

• Diarrhoea

Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Jaundice
• Intestinal obstruction
• Acute ulcerative colitis
• Diarrhoea associated with pseudomembranous enterocolitis
• Raised intracranial pressure
• Head injury
• Myasthenia gravis
• Pyloric stenosis
• Paralytic ileus
• Prostatic enlargement

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Severe dehydration
• Electrolyte imbalance
• Ulcerative colitis
• Down's syndrome

Forms avail. in SA and covered in this monograph: tab

Acute diarrhoea - Mild to moderate

Diphenoxylate/ Atropine
2.5/0.025 (mg)

• Oral (tab): Loading dose: 4 tab, as a single dose; Maintenance: 2 tab, 6hrly; Max: 10 tab/24hrs

Paed. forms avail. in SA and covered in this monograph: tab

Acute diarrhoea - Mild to moderate

Diphenoxylate/ Atropine
2.5/0.025 (mg)

• Younger than 4 years: Not established for use
• Between 4-8 years: Oral (tab): 1 tab, 8hrly
• Between 9-12 years: Oral (tab): 1 tab, 6hrly
• Older than 12 years: See adult dosage

Recommendations for this combination product as per highest risk category when comparing individual active ingredients

Pregnancy

• Caution (Diphenoxylate, Atropine)
• No studies have been conducted to establish safety in pregnancy.  Diphenoxylate should be given only if the potential benefit justifies the potential risk to foetus
• Atropine sulfate crosses the placenta. There is insufficient evidence to establish the safety of atropine in human pregnancy. It should, therefore, be used during pregnancy only if considered essential by the physician

Breastfeeding

• Caution; not recommended (Diphenoxylate, Atropine)
• Data on breastfeeding is unavailable to determine risk. Diphenoxylate is lipophilic, with a large volume of distribution and is expected to be excreted in breast milk. Alternatives should be considered
• Atropine sulfate is excreted in breast milk, and infants of nursing mothers may exhibit some effects of the drug. Infants are usually very sensitive to the effects of anticholinergic drugs. Atropine should therefore only be used during breastfeeding if considered essential

Renal Impairment

• Caution; no dose adjustment recommended (Diphenoxylate, Atropine)

Hepatic Impairment

• Mild to moderate: Caution; no dose adjustment recommended (Diphenoxylate, Atropine)
• Severe: Contraindicated (Diphenoxylate)

Elderly

• Caution; no dose adjustment recommended (Diphenoxylate, Atropine)

Porphyria Information

• Not yet classified (NC)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Malaise
• Lethargy
• Sedation
• Somnolence
• Confusion
• Dizziness
• Restlessness
• Depression
• Euphoria
• Hallucinations
• Headache

Cardiovascular Disorders

• Arrhythmias
• Bradycardia
• Palpitations

Respiratory Disorders

• Respiratory depression

Gastrointestinal Disorders

• Paralytic ileus
• Toxic megacolon
• Nausea and vomiting
• Abdominal discomfort
• Constipation
• Anorexia
• Dry mouth

Genitourinary Disorders

• Urinary retention
• Difficulty in micturition

Skin and Subcutaneous Tissue Disorders

• Flushing
• Dry skin 

Immune, Blood and Lymphatic System Disorders

• Fever
• Anaphylaxis
• Angioedema
• Urticaria
• Pruritus

Sensory Disorders

• Increased intraocular pressure
• Mydriasis
• Blurred vision
• Photophobia
• Closed angle glaucoma

• Domperidone
• Metoclopramide
• Bethanecol
• Carbachol
• Cisapride
• Galantamine
• Neostigmine
• Pyridostigmine
• Pilocarpine
• Amantadine
• Anthihistamines 
• Clozapine
• Disopyramide
• Fluspiriline
• Loxapine
• Monoamine oxidase inhibitors
• Nefopam
• Olanzapine
• Phenothiazines
• Quantiapine
• Remoxipride
• Terfenadine
• Tricyclic antidepressants
• Zotepine
• Dompezil
• Memantine
• Levodopa
• Ketoconazole

None routine

Diphenoxylate
Diphenoxylate inhibits peristalsis via stimulation of mu and delta opiate receptors in the bowel, resulting in a prolonged gastric transit time. This causes increased absorption of water in the large intestine leading to constipation.

Atropine
Atropine is an antimuscarinic agent which acts as a competitive inhibitor of acetylcholine at the muscarinic receptors of autonomic effector sites with parasympathetic innervation. This anticholinergic action is thought to relieve gastrointesinal smooth muscle spasm.

COMBINATION PREPARATIONS

Diphenoxylate/ Atropine

Tablet 2.5mg/0.025mg

• Lomotil (Johnson & Johnson) originator