Chlordiazepoxide in Pregnancy and Breastfeeding

Risk Factor: DM
Class: Central nervous system drugs / Sedatives and hypnotics

Contents of this page:
Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

Chlordiazepoxide is a benzodiazepine (see also Diazepam). The drug has antianxiety, sedative, appetite-stimulating, and weak analgesic actions (1).

No teratogenic effects were observed in rats given doses of 1080 mg/kg/day through one or two matings (1). At 100 mg/kg/day, maternal toxicity (decreased interest in mating and nursing) and marked decreases in offspring viability and body weight were attributed to sedative effects of the drug (1). Moreover, at this dose, one newborn in each of two matings had major skeletal abnormalities.

In a study evaluating 19,044 live births, the use of chlordiazepoxide was associated with a greater than 4-fold increase in severe congenital anomalies (2). In 172 patients exposed to the drug during the first 42 days of gestation, the following defects were observed: mental deficiency, spastic diplegia and deafness, microcephaly and retardation, duodenal atresia, and Meckel's diverticulum (2). Although not statistically significant, an increased fetal death rate was also found with maternal chlordiazepoxide ingestion (2). A survey of 390 infants with congenital heart disease matched with 1,254 normal infants found a higher rate of exposure to several drugs, including chlordiazepoxide, in the offspring with defects (3).

In contrast, other studies have not confirmed a relationship with increased defects or mortality (4,5,6,7 and 8). The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 257 of which were exposed in the 1st trimester to chlordiazepoxide (5,8). No association with large classes of malformations or to individual defects was found.

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 788 newborns had been exposed to chlordiazepoxide during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 44 (5.6%) major birth defects were observed (34 expected). Specific data were available for six defect categories, including (observed/expected) 10/7 cardiovascular defects, 2/1 oral clefts, 0/0.5 spina bifida, 3/2 polydactyly, 1/1 limb reduction defects, and 2/2 hypospadias. These data do not support an association between the drug and congenital defects.

A 1992 study reported on heavy benzodiazepine exposure during pregnancy from Michigan Medicaid data collected during 1980 to 1983 (9). Of the 2,048 women, from a total sample of 104,339, who had received benzodiazepines, 80 had received 10 or more prescriptions for these agents. The records of these 80 women indicated frequent alcohol and substance abuse. Their pregnancy outcomes were 3 intrauterine deaths, 2 neonatal deaths in infants with congenital malformations, and 64 survivors. The outcome for 11 infants was unknown. Six of the surviving infants had diagnoses consistent with congenital defects (9). The investigators concluded that the high rate of congenital anomalies was suggestive of multiple alcohol and substance abuse and may not have been related to benzodiazepine exposure (9).

Neonatal withdrawal consisting of severe tremulousness and irritability has been attributed to maternal use of chlordiazepoxide (10). The onset of withdrawal symptoms occurred on the 26th day of life. Chlordiazepoxide readily crosses the placenta at term in an approximate 1:1 ratio (11,12 and 13). The drug has been used to reduce pain during labor, but the maternal benefit was not significant (14,15). Marked depression was observed in three infants whose mothers received chlordiazepoxide within a few hours of delivery (13). The infants were unresponsive, hypotonic, hypothermic, and fed poorly. Hypotonicity persisted for up to a week. Other studies have not seen depression (11,12).

Breast Feeding Summary

No reports describing the use of chlordiazepoxide during human lactation or measuring the amount, if any, excreted into breast milk have been located. The molecular weight (about 300) is low enough, however, that passage into milk should be expected. Moreover, other benzodiazepines are excreted into milk and have produced adverse effects in nursing infants (see Diazepam). Because of the potential for drug accumulation and toxicity in nursing infants, chlordiazepoxide should be avoided during breast feeding.

References

  1. Product information. Librium. ICN Pharmaceuticals, 2000.
  2. Milkovich L, van den Berg BJ. Effects of prenatal meprobamate and chlordiazepoxide hydrochloride on human embryonic and fetal development. N Engl J Med 1974;291:126871.
  3. Rothman KJ, Fyler DC, Golblatt A, Kreidberg MB. Exogenous hormones and other drug exposures of children with congenital heart disease. Am J Epidemiol 1979;109:4339.
  4. Crombie DL, Pinsent RJ, Fleming DM, Rumeau-Rouguette C, Goujard J, Huel G. Fetal effects of tranquilizers in pregnancy. N Engl J Med 1975;293:1989.
  5. Hartz SC, Heinonen OP, Shapiro S, Siskind V, Slone D. Antenatal exposure to meprobamate and chlordiazepoxide in relation to malformations, mental development, and childhood mortality. N Engl J Med 1975;292:7268.
  6. Bracken MB, Holford TR. Exposure to prescribed drugs in pregnancy and association with congenital malformations. Obstet Gynecol 1981;58:33644.
  7. Committee on Drugs, American Academy of Pediatrics. Psychotropic drugs in pregnancy and lactation. Pediatrics 1982;69:2414.
  8. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977:3367.
  9. Bergman U, Rosa FW, Baum C, Wiholm B-E, Faich GA. Effects of exposure to benzodiazepine during fetal life. Lancet 1992;340:6946.
  10. Athinarayanan P, Pierog SH, Nigam SK, Glass L. Chlordiazepoxide withdrawal in the neonate. Am J Obstet Gynecol 1976;124:2123.
  11. Decancq HG Jr, Bosco JR, Townsend EH Jr. Chlordiazepoxide in labour: its effect on the newborn infant. J Pediatr 1965;67:83640.
  12. Mark PM, Hamel J. Librium for patients in labor. Obstet Gynecol 1968;32:18894.
  13. Stirrat GM, Edington PT, Berry DJ. Transplacental passage of chlordiazepoxide. Br Med J 1974;2:729.
  14. Duckman S, Spina T, Attardi M, Meyer A. Double-blind study of chlordiazepoxide in obstetrics. Obstet Gynecol 1964;24:6015.
  15. Kanto JH. Use of benzodiazepines during pregnancy, labour and lactation, with particular Reference to pharmacokinetic considerations. Drugs 1982;23:35480.

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Questions and Answers

chlordiazepoxide?, acholoh abuse

Chlordiazepoxide is a third-generation benzodiazapene, which binds to GABA receptors in the central nervous system and enhances the effects of GABA. It is often used for alcohol withdrawal and moderate-to-severe anxiety. It can cause drowsiness, confusion, mood changes, nausea, ataxia, and extrapyramidal effects (similar to any other benzodiazapene). It is metabolized by the liver and excreted in the urine, so caution should be used in patients with liver or kidney disease. It should not be taken with sodium oxybate and should only be used with other sedative/hypnotic medications under close supervision by a physician.

Why am I not having any side effects from Chlordiazepoxide?, I have just finished my second day of taking this, and was told I would feel drowsy and drunk, with a whole host of other side effects. I am taking a high dose, but am not feeling anything at all, even though I am supposed to. The whole point of taking it is to feel these side effects, so why aren't I feeling anything?

For those who don''t know, Chlordiazepoxide is similar to Valiuam, and is also know as Librium.

It may take a little longer to build up in your system. Or some people dont suffer side effects with drugs.

Can taking Chlordiazepoxide couse dehidration or dryness of mouth, eyes and skin?, I have been taking Chlordiazepoxide for about 4 months now and now im having very dry mouth , eyes and skin.

Chlordiazepoxide – Librium – I list some of the most usual and some of the not so usual side effects of Librium, and if these occur, what action you should take. Drowsiness, dizziness, nausea, constipation, blurred vision, or headache may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly. Tell your doctor immediately if any of these unlikely but serious side effects occur: mental/mood changes, slurred speech, clumsiness, trouble walking, decreased/increased interest in sex, tremor, uncontrollable movements, facial or muscle twitching, trouble urinating, sleep disturbances. Tell your doctor immediately if any of these highly unlikely but very serious side effects occur: fainting, stomach/abdominal pain, persistent nausea, vomiting, fatigue, yellowing eyes or skin, dark urine, persistent sore throat or fever. A serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching, swelling, severe dizziness, trouble breathing. If you notice other effects not listed above, contact your doctor or pharmacist. Note that a dry mouth and skin is not amongst these, but if the condition is concerning you, you would be advised to speak first, to your pharmacist. If you are taking any other medication at the same time, you need to inform the pharmacist who will check for adverse drug interactions.
I add a link that contains details about Librium

http://www.rxlist.com/cgi/
generic/chlordia_ad.htm

Hope this helps
Matador 89

what is Chlordiazepoxide and can i take 2 at the same time?, i take Chlordiazepoxide(librax) 0.5 milligrams and it says i have to take it it twice a day can i take 2 at the same time? will it do anything bad to me or will it lead to addiction or abuse? casue i have alot anxiety and im thinking that a higher dosage will help

this is a miracle. i am surfing this sight and stop to find my bottle of that stuff for anxiety and panic. about to slam down a couple. then i see your posting. isn't that something? yeh, it is very addictive. i tried to stop last week and within three or four days i felt those feelings and nasea returning. they say stop it for sure after six to eight months. i say it takes a lot less time than that. it makes you forgetful and stumble and drop things. but no panic attacks. so go from there to an expert, which doesn't include me.

Hi, iam an alcoholic and have started a home detox plan this morning using chlordiazepoxide?, is it ok to take a diazepam tablet tonight to help me try to sleep because im finding it impossible, also any other tips to get through this horrendace moment would be greatly appreciated, thank you so much.

I have a friend who has been an alcoholic for years now and i have to watch him drink himself to death slowly. I admire you and hope you succeed in beating this illness and i pray my friend will follow suit soon. Good luck.

Hi, i am currently on my third day of an alchol detox am taking chlordiazepoxide, today i am taking 10mg?, tablets (8am,midday,6pm,10pm), i have lost my sheet of paper my doctor gave me and cannot remember the remaing course or reducing the tablets, ive tried to get hold of my doctor but cant, i think its reducing it by 10mg every day, can any one help because im getting a bit panicky, many thanks.

You can go here and read up about the dosage and how the medication is usually administered. It should also tell you how the medicine is reduced and other uses for it. This website is as good as a PDR, and better because one does not have to spend 90 dollars in order to get it! Just type in the name of the RX and go from there. Good luck, and I would try your M.D. tomorrow many take Monday's and Friday's off. Have a good one! =)
http://www.rxlist.com/script/main/hp.asp

Does Chlordiazepoxide contain asprin?, I have to get an EGD done in a week and am not allowed to take any products containing asprin in the week leading up to the procedure. This is an anti anxiety drug I sometimes take to getto sleep. Also any GOOD muscle pain killers anyone could recommend that don't contain asprin would be great. (other than tylenol - that doesn't work very well for me.) Thanks!

Simple......Clordiazepoxide Hydrochloride AKA Librium, Novo Poxide, and Apo Chlordiazepoxide belong to a family of drugs known as the benodiazepines. NO it DOES NOT CONTAIN ASPIRIN. These drugs as you said are given generally for apprehension, anxiety, or sleep. I am sure the reason you are having an EGD is to rule out bleeding in your esophagus, stomach, and duodenum. (or any other type pathology). If you take ASA or aspirin, one of the side effects is GI bleeding (gastro intestinal) and if you take aspirin they will not know if the bleeding is caused from ulcers, etc. or the aspirin. Ask your pharmacist to recommend any NSAID (non steroidal anti inflammatory drug) but you must not overdo on those either, cuz they can cause GI upset and bleeding as well. (Less likely however) Good Luck...............