Atropinism

Since a subtherapeutic dose of atropine has been added to Lomotil, consideration should be given to the development of adverse reactions associated with atropine (see WARNINGS). Lomotil has caused atropinism (hyperthermia, tachycardia, urinary retention, flushing, dryness of the skin and mucous membranes) particularly in pediatric patients with Down's syndrome. Lomotil is not indicated for use in pediatric patients (see CONTRAINDICATIONS and WARNINGS). Monitor patients for signs of atropinism.

Information for patients:

Advise patients:

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Accidental ingestion of Lomotil in children, especially in those less than 6 years of age, may result in severe respiratory depression or coma. Instruct patients to take steps to store Lomotil securely and out of reach of children, and to dispose of unused Lomotil (see WARNINGS).

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To take Lomotil at the prescribed dosage. Use of a higher than prescribed dosage may include opioid and/or anticholinergic effects (see OVERDOSAGE). Report to a healthcare facility if they develop anticholinergic symptoms such as hyperthermia, flushing, tachycardia, tachypnea, hypotonia, lethargy, hallucinations, febrile convulsion, dry mouth, mydriasis or opioid symptoms such as progressive CNS and respiratory depression, miosis, seizures, or paralytic ileus.

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Lomotil may produce drowsiness or dizziness. Concomitant use of alcohol or other drugs that also cause CNS depression (e.g., barbiturates, benzodiazepines, opioids, buspirone, antihistamines, and muscle relaxants) may increase this effect. Inform patients not to operate motor vehicles or other dangerous machinery until they are reasonably certain that Lomotil does not affect them adversely.

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To use fluid and electrolyte therapy, if prescribed along with Lomotil, as instructed by their healthcare provider.

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Clinical improvement of diarrhea is usually observed within 48 hours. If clinical improvement is not seen within 10 days, discontinue Lomotil and contact their healthcare provider.

Drug interactions:

Carcinogenesis, mutagenesis, impairment of fertility

No long-term study in animals has been performed to evaluate carcinogenic potential. Diphenoxylate hydrochloride was administered to male and female rats in their diets to provide dose levels of 4 and 20 mg/kg/day throughout a three-litter reproduction study. At 50 times the human dose (20 mg/kg/day), female weight gain was reduced and there was a marked effect on fertility as only 4 of 27 females became pregnant in three test breedings. The relevance of this finding to usage of Lomotil in humans is unknown.

Pregnancy

Diphenoxylate hydrochloride has been shown to have an effect on fertility in rats when given in doses 50 times the human dose (see above discussion). Other findings in this study include a decrease in maternal weight gain of 30% at 20 mg/kg/day and of 10% at 4 mg/kg/day. At 10 times the human dose (4 mg/kg/day), average litter size was slightly reduced.

Teratology studies were conducted in rats, rabbits, and mice with diphenoxylate hydrochloride at oral doses of 0.4 to 20 mg/kg/day. Due to experimental design and small numbers of litters, embryotoxic, fetotoxic, or teratogenic effects cannot be adequately assessed. However, examination of the available fetuses did not reveal any indication of teratogenicity.

There are no adequate and well-controlled studies in pregnant women. Lomotil should be used during pregnancy only if the anticipated benefit justifies the potential risk to the fetus.

Nursing mothers

Caution should be exercised when Lomotil is administered to a nursing woman, since the physicochemical characteristics of the major metabolite, diphenoxylic acid, are such that it may be excreted in breast milk and since it is known that atropine is excreted in breast milk.

Pediatric use

The safety and effectiveness of Lomotil have been established in pediatric patients 13 years of age and older as adjunctive therapy in the management of diarrhea. The safety and effectiveness of Lomotil have not been established in pediatric patients less than 13 years of age.

Lomotil is contraindicated in pediatric patients less than 6 years of age due to the risks of severe respiratory depression and coma, possibly resulting in permanent brain damage or death (see CONTRAINDICATIONS).

Lomotil has caused atropinism, particularly in pediatric patients with Down's syndrome (see PRECAUTIONS).

In case of accidental ingestion of Lomotil by pediatric patients, see OVERDOSAGE for recommended treatment.