Lomotil Product Monograph

Drug Interactions

LOMOTIL may potentiate the action of barbiturates, tranquilizers and alcohol. Therefore, the patient should be closely observed when these medications are used concomitantly.

Since the chemical structure of diphenoxylate is similar to that of meperidine, the concurrent use of LOMOTIL with monoamine oxidase inhibitors may in theory precipitate a hypertensive crisis.

CNS depression, dizziness or drowsiness may be potentiated with the concomitant use of LOMOTIL with other CNS depressants.

ADVERSE EFFECTS

The most frequently reported adverse effect is nausea. Other symptoms which have been reported at therapeutic doses are:

General Disorders: Malaise

Nervous System: Drowsiness, coma, lethargy, sedation/drowsiness, restlessness, dizziness, insomnia, headache, blurring of vision, depression, euphoria, confusion, paraesthesia, hallucination, somnolence

Respiratory: Respiratory depression

GI: Vomiting, anorexia, nausea, abdominal bloating, abdominal discomfort, cramps, paralytic ileus, toxic megacolon, pancreatitis, gastrointestinal disorder

Allergy: Anaphylaxis, pruritis, skin eruption, giant urticaria, angioedema.

Atropine sulfate effects such as dryness of the skin and mucous membranes, hyperthermia, tachycardia, urinary retention and flushing may also occur, especially in children.

SYMPTOMS AND TREATMENT OF OVERDOSAGE

Diphenoxylate hydrocholoride with atropine sulfate should be kept in a child-resistant container and out of the reach of children since overdosage may lead to severe respiratory depression and coma, possibly leading to permanent brain damage or death (See WARNINGS).

Symptoms

Initial signs of overdosage with LOMOTIL (diphenoxylate hydrochloride with atropine sulfate) may include dryness of the skin and mucous membranes, mydriasis, restlessness, flushing, hyperthermia and tachycardia followed by lethargy or coma, hypotonic reflexes, nystagmus, pinpoint pupils, tachypnea, toxic encephalopathy, seizures, and severe respiratory depression. Cardiac arrest has occurred in children.

Treatment

Treat all possible LOMOTIL overdoses as serious and maintain medical observation for at least 48 hours.

Gastric lavage, establishment of a patent airway, and possibly, mechanically-assisted respiration are advised. Gastric lavage should be undertaken with due caution in an unconscious patient, preferably following insertion of a cuffed endotracheal tube. If the patient is not comatose, administration of a slurry of activated charcoal may be indicated.

Narcotic antagonists such as Naloxone hydrochloride may be used for the treatment of respiratory depression caused by narcotic drugs or pharmacologically- related compounds, such as LOMOTIL.

Naloxone hydrochloride Dosage in Adults

Naloxone hydrochloride may be administered to adults at a dose of 0.4 mg intravenously. Additional doses of 0.4 mg may be given at 2- or 3-minute intervals until adequate improvement in pulmonary ventilation is demonstrated. Subsequent injections of this drug must be governed by the degree of respiratory depression present and should be titrated accordingly. Since the duration of action of naloxone hydrochloride is short in comparison to that of diphenoxylate hydrochloride improvement of respiration after its administration may be followed by subsequent respiratory depression. It should be noted that although signs of overdosage and respiratory depression may not be evident with LOMOTIL after ingestion, respiratory depression may occur 12 to 30 hours later. Consequently, continuous observation is necessary until the effect of diphenoxylate hydrochloride on respiration, which may persist for many hours, has passed. The period of observation should extend over at least 48 hours, preferably under continuous hospital care.

Naloxone hydrochloride Dosage in Children

For known or suspected narcotic overdosage, the initial dosage of Naloxone hydrochloride in children is 0.005 - 0.01 mg/kg body weight when given intravenously, intramuscularly, or subcutaneously. This dose can be repeated as for adults above. If necessary, Naloxone hydrochloride can be diluted with Sterile Water for Injection.

DOSAGE AND ADMINISTRATION

Adults

The usual initial dose of LOMOTIL (diphenoxylate hydrochloride with atropine sulfate) is 5 mg (2 tablets) 3 or 4 times daily (20 mg/24 hrs in divided doses is the maximum recommended dosage). An individual maintenance dose can be subsequently determined. Downward adjustment should be made as soon as initial control of symptoms is accomplished. The maintenance dose may be as low as 1/4 of the dose required for initial control.

Children

NOT FOR USE IN CHILDREN UNDER FOUR YEARS OF AGE (SEE WARNINGS AND PRECAUTIONS).

The recommended initial dosage of LOMOTIL determined by the child's weight, is as follows:

0.3 - 0.4 mg/kg daily in divided doses

For convenience, approximate dosage (in children of average weight) may be determined by the following table:

As with adult therapy, adjustment of dosage downward should be made as soon as initial control of symptoms is accomplished.

These pediatric schedules are the best approximation of an average dose recommendation which should be adjusted according to the overall nutritional status and degree of dehydration encountered in the child. The recommended doses must not be exceeded.

AVAILABILITY OF DOSAGE FORMS

Tablets - Each white, round tablet with "SEARLE" debossed on one side and 61 on the other side, contains 2.5 mg of diphenoxylate hydrochloride and 0.025 mg of atropine sulfate.

Non-medicinal ingredients: acacia, corn starch, mineral oil, magnesium stearate, sorbitol, sucrose, talc.

Tablets are available in bottles of 250.

Store at 15-25°C and protect from light.

LOMOTIL is a narcotic drug.

PHARMACEUTICAL INFORMATION

Proper Name: Diphenoxylate hydrochloride

Common Name: 1-(3-cyano-3,3-diphenylpropyl)-4-phenylpiperidine-4-carboxylate

Structural formula:

Empirical Formula: C₃₀H₃₂N₂O₂•HCl

Molecular Weight: 489.06

Physical Form: White, odorless crystalline powder

Solubility (at 25^oC, mg/mL): Acetic Acid 500

Chloroform 360

Methanol >50

Ethanol 3

Water 0.8

Melting Point: 220.5 - 222°C

pH: 3.3 (Saturated aqueous solution)

pKa: 7.1

Proper Name: Atropine sulfate

Common Name: tropan-3α-ylrac-(2R)-3-hydroxy-2-phenylpropanoate

Structural formula:

Empirical Formula: 2 (C₁₇H₂₃NO₃)•H₂SO₄•H₂O

Molecular Weight: 694.84

Physical Form: Odorless, colourless crystals or white crystalline powder

Solubility: 1 g dissolves in 0.4 mL water

2.5 mL boil. alc.

2.5 mL glycerol

420 mL chloroform

3000 mL ether

Melting Point: 190 - 194°C

pH: 5.4

pKa: 9.9 (20°)