Diphenoxylate

 Risk Factor: CM
 Class: GASTROINTESTINAL AGENTS / Antidiarrheals

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

Diphenoxylate is a narcotic related to meperidine. It is available only in combination with atropine (to discourage overdosage) for the treatment of diarrhea. Diphenoxylate is rapidly metabolized to diphenoxylic acid (difenoxin), a biologically active metabolite (1).

Reproduction studies have been conducted in mice, rats, and rabbits with oral doses of 0.4 to 20 mg/kg/day (1). Because of the experimental design and small numbers of litters, embryotoxic, fetotoxic, and teratogenic effects could not be adequately assessed, but examination of the available fetuses did not reveal any evidence of teratogenicity (1).

No reports describing the placental transfer of diphenoxylate to the fetus have been located. The molecular weight of the active, major metabolite defenoxin (461 for the hydrochloride salt) is low enough that the presence of this agent in the fetus should be expected.

In one study, no malformed infants were observed after 1st trimester exposure in seven patients (2). A single case of a female infant born at 36 weeks' gestation with multiple defects, including Ebstein's anomaly, was described in a 1989 report (3). In addition to the cardiac defect, other abnormalities noted were hypertelorism, epicanthal folds, low-set posteriorly rotated ears, a cleft uvula, medially rotated hands, deafness, and blindness. The mother had taken Lomotil (diphenoxylate and atropine) for diarrhea during the 10th week of gestation. Since exposure was beyond the susceptible stages of development for these defects, the drug combination was not considered causative. A possible viremia in the mother as a cause of the diarrhea and the defects could not be excluded.

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 179 newborns had been exposed to diphenoxylate (presumably combined with atropine) during the 1st trimester (F. Rosa, personal communication, FDA, 1993). Nine (5.0%) major birth defects were observed (seven expected). Specific data were available for six defect categories, including (observed/expected) 3/2 cardiovascular defects, 0/0.3 oral clefts, 1/0 spina bifida, 1/0.5 polydactyly, 1/0.3 limb reduction defects, and 1/0.4 hypospadias. These data do not support an association between the drug and congenital defects.

Breast Feeding Summary

The manufacturer reports that the active metabolite, diphenoxylic acid (difenoxin), is probably excreted into breast milk, and the effects of that drug and atropine may be evident in the nursing infant (1). One source recommends that the drug should not be used in lactating mothers (4). However, the American Academy of Pediatrics considers atropine (diphenoxylate was not listed) to be compatible with breast feeding (5).

References

1. Product information. Lomotil. G.D. Searle and Company, 2000.
2. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977:287.
3. Siebert JR, Barr M Jr, Jackson JC, Benjamin DR. Ebstein's anomaly and extracardiac defects. Am J Dis Child 1989;143:5702.
4. Stewart JJ. Gastrointestinal drugs. In Wilson JT, ed. Drugs in Breast Milk. Balgowlah, Australia:ADIS Press, 1981:71.
5. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.
   
   

Questions and Answers

mix of diphenoxylate and chlordizepoxide, whats the effect?, my friend took those two drugs together with alcohol i think, now he is asleep... what are the effects of taking those two drugs together? i know diphenoxylate is an opiate but thats about it

ive done that before i went perdy crazy my friends say they said i passed out woke up tryed to commit scuicidealmost stab someone and passed out agoain and i didnt remember any of it so keep that crazy ***** in line when he wakes up *****!
=]=]

can Diphenoxylate and atropine made in ayurvedic form if yes than how ?,

"Ayurveda" is based on "ancient wisdom", not modern organic chemistry, so your question makes no sense and the answer has to be "of course not!"

It's a bit like asking what Brahmanaspati's teaching were on video games!

can diphenoxylate or metoclopramide get you high?, im not asking this because im trying to get high im asking this because my roomate does try to get high from pills so i was wondering if i should lock these up or not? can you get high off of them it says that diphenoxylate is an opioid and both perscriptions say may cause drowziness so please let me kno if they can cause a high or not

thanks

diphenoxylate is classified as a controlled substance so I would imagine so. Any opiate can get you high if taken the proper amount.