Cimetidine

 Risk Factor: BM
 Class: GASTROINTESTINAL AGENTS / Antisecretory Agents

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

Cimetidine is an H2-receptor antagonist that inhibits gastric acid secretion. In pregnancy, the antihistamine is primarily used for the treatment of peptic ulcer disease and for the prevention of gastric acid aspiration (Mendelson's syndrome) prior to delivery.

In studies with multiple animal species, no evidence of impaired fertility or teratogenesis was observed with doses up to 40 times higher than the usual human dose (1). Cimetidine does have weak antiandrogenic effects in animals, as evidenced by a reduction in the size of testes, prostatic glands, and seminal vesicles (2,3), and in humans, by reports of decreased libido and impotence (4). Conflicting reports on the antiandrogenic activity in animals exposed in utero to cimetidine have been published (5,6,7,8 and 9).

Three References, all from the same research group, described the effects on male rats of exposure to cimetidine from gestation up to the time of weaning (5,6 and 7). The rats had decreased weights of testicles, prostate gland, and seminal vesicles at 55 and 110 days of age as compared to nonexposed controls. Exposed animals also had reduced testosterone serum levels, lack of sexual motivation, and decreased sexual performance, but normal luteinizing hormone levels. The observed demasculinization effects were still present 35 days after discontinuation of the drug, indicating that exposure may have modified both central and end-organ androgen receptor activity or responsiveness (5,6 and 7). In contrast, researchers from the manufacturer treated rats similarly to rats in the above reports and found no effect on any of the parameters described previously (8). Another group found no effect of cimetidine exposure during gestation and lactation on masculine sexual development, except for an insensitivity of the pituitary gland to androgen regulation, and no effect at all on female pups (9). These authors concluded that cimetidine was not an animal teratogen.

Cimetidine crosses the placenta to the fetus by simple diffusion (10,11,12,13 and 14). In an in vitro study, the placental transfer of cimetidine across human and baboon placentas was similar (10). Cimetidine is not metabolized by the placenta (11). At term, cimetidine crosses the placenta, resulting in a peak mean fetal:maternal ratio of 0.84 at 1.52 hours (12). In an earlier study, 20 women were administered a single, 200-mg bolus injection of cimetidine prior to delivery (19 vaginal, 1 cesarean section) (13). The drug was detected in all but two cord blood samples with levels ranging from 0.051.22 g/mL. The injection-to-delivery intervals in the two patients with no cimetidine in cord blood were prolonged, 435 and 780 minutes. A 1983 study measured a peak mean fetal:maternal ratio of about 0.5 at 2.5 hours (14).

The manufacturer has received a number of reports of women who took the drug during pregnancy, including throughout gestation (B. Dickson, personal communication, Smith Kline & French Laboratories, 1986). They are aware of three isolated incidences of congenital defects, apparently unrelated to cimetidine therapy, including congenital heart disease, mental retardation detected later in life, and clubfoot.

The drug has been used throughout pregnancy in a case ending in intrauterine fetal death, but the adverse outcome was believed to be due to severe maternal disease and captopril therapy (see Captopril) (15). Three pregnant women with gastric hemorrhage secondary to peptic ulcer disease were described in a 1982 report (16). The women, at 16, 12, and 31 weeks' gestation, were treated for various lengths of time with cimetidine and other standard therapy and all delivered healthy newborns without congenital defects or metabolic disturbances. Transient liver impairment has been described in a newborn exposed to cimetidine at term (17). However, other reports have not confirmed this toxicity (13,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34 and 35).

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 460 newborns had been exposed to cimetidine during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 20 (4.3%) major birth defects were observed (20 expected). Specific data were available for six defect categories, including (observed/expected) 8/5 cardiovascular defects, 0/1 oral clefts, 0/0 spina bifida, 1/1 polydactyly, 0/1 limb reduction defects, and 1/1 hypospadias. These data do not support an association between the drug and congenital defects.

Cimetidine has been used at term either with or without other antacids to prevent maternal gastric acid aspiration pneumonitis (Mendelson's syndrome) (13,14,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34 and 35). No neonatal adverse effects were noted in these studies.

Data from the Swedish Medical Birth Registry were presented in 1998 (36). A total of 553 infants (6 sets of twins) were delivered from 547 women who had used acid-suppressing drugs early in pregnancy. A number of other pharmaceutical agents, identified only by drug category, were also used by these women. Seventeen infants with birth defects were identified (3.1%; 95% confidence interval [CI] 1.84.9) compared with the crude malformation rate of 3.9% in the Registry. The odds ratio (OR) for a congenital malformation, stratified for birth year, maternal age, parity, and smoking was 0.72 (95% CI 0.411.24 (36). The OR for malformations after proton pump blocker exposure was 0.91 (95% CI 0.451.84) compared with 0.46 (95% CI 0.171.20) for H2-receptor antagonists (OR 0.86, 95% CI 0.332.23; p=0.13). Of the 17 infants with birth defects, 10 had been exposed to proton pump blockers, 6 to H2 antagonists, and 1 to both classes of drug. Cimetidine was the only acid-suppressing drug exposure in 35 infants. Three other offspring were exposed in utero to cimetidine combined either with famotidine (one infant) or with omeprazole (two infants). Two birth defects (5.7%) were observed in the group where cimetidine was the only acid-suppressing agent used. The defects were an encephalocele and an unstable hip (36).

Two databases, one from England and the other from Italy, were combined for a study published in 1999 that was designed to assess the incidence of congenital malformations in women who had received a prescription during the 1st trimester for an acid-suppressing drug (cimetidine, ranitidine, and omeprazole) (37). Nonexposed women were selected from the same databases to form a control group. Spontaneous abortions and elective abortions (except two cases for anomalies that were grouped with stillbirths) were excluded from the analysis. Stillbirths were defined as any pregnancy loss occurring at 28 weeks' gestation or later. Cimetidine was taken in 233 pregnancies, resulting in 234 live births (14 [6.0%] premature), 3 stillbirths, and 1 neonatal death. Eleven (4.7%) of the newborns had a congenital malformation (shown by system): craniofacial (cleft lip and palate), musculoskeletal (dysplastic hip/dislocation/clicking hip N=3; polydactyly), genital and urinary (hypospadias N=2; congenital hydrocele/inguinal hernia, ovarian cyst, renal defects/hydronephrosis), and gastrointestinal (pyloric stenosis). In addition, two newborns had a small head circumference for gestational age. In comparison, the outcomes of 1,547 nonexposed pregnancies included 1,560 live births (115 [7.4%] premature), 15 stillbirths (includes 2 elective abortions for anomalies), and 10 neonatal deaths. Sixty-four (4.1%) of the newborns had malformations involving the following: central nervous system (N=2), head/face (N=13), eye (N=2), heart (N=7), muscle/skeletal (N=13), genital/urinary (N=18), gastrointestinal (N=2), and those of polyformation (N=3) or known genetic defects (N=4). There were 21 newborns that were small for gestational age and 78 had a small head circumference for gestational age. The relative risk of malformation (adjusted for mother's age and prematurity) associated with cimetidine was 1.3 (95% CI 0.72.6), with omeprazole 0.9 (95% CI 0.42.4), and with ranitidine 1.5 (95% CI 0.92.6) (37).

In summary, no increased risk of congenital malformations attributable to cimetidine in humans have been reported. One group of reviewers has recommended that the drug not be used during pregnancy because of the possibility for feminization, as observed in some animals and in nonpregnant humans (38). Apparently, this potential toxicity has not been studied in humans exposed in utero to cimetidine, but research in this area is warranted.

Breast Feeding Summary

In a study using lactating mice, drug-metabolizing enzymes in nursing pups were inhibited to a greater extent by cimetidine than those in the mother (39). Mouse dams were treated with cimetidine from the delivery date to 6 weeks, the time of weaning. Male pups were adversely affected from 4 weeks of age to 8 weeks, 2 weeks after cessation of exposure, whereas female pups were affected for a longer time, commencing at 2 weeks of age and continuing up to 810 weeks. The effects on enzyme activity were completely resolved in both sexes at 10 weeks of age.

Cimetidine is excreted into breast milk and may accumulate in concentrations greater than that found in maternal plasma (40). Following a single 400-mg oral dose a theoretical milk:plasma ratio of 1.6 has been calculated (40). Multiple oral doses of 200 and 400 mg result in milk:plasma ratios of 4.6 to 7.44, respectively. An estimated 6 mg of cimetidine per liter of milk could be ingested by the nursing infant. The results of a study published in 1995 suggested that cimetidine was actively transported into milk (41). Using single oral doses of 100, 600, or 1200 mg in healthy lactating volunteers, the average of the mean milk:serum ratios for the three doses was 5.77 (range 5.655.84), much higher than that predicted by diffusion (41).

The clinical significance of an infant ingesting cimetidine from milk is unknown. Theoretically, the drug could adversely affect the nursing infant's gastric acidity, inhibit drug metabolism, and produce central nervous system stimulation, but these effects have not been reported. The American Academy of Pediatrics has classified the drug as compatible with breast feeding (42).

References

1. Product information. Tagamet. SmithKline Beecham Pharmaceuticals, 2000.
2. Finkelstein W, Isselbacher KJ. Cimetidine. N Engl J Med 1978;299:9926.
3. Pinelli F, Trivulzio S, Colombo R, Cocchi D, Faravelli R, Caviezel F, Galmozzi G, Cavallaro R. Antiprostatic effect of cimetidine in rats. Agents Actions 1987;22:197201.
4. Sawyer D, Conner CS, Scalley R. Cimetidine: adverse reactions and acute toxicity. Am J Hosp Pharm 1981;38:18897.
5. Anand S, Van Thiel DH. Prenatal and neonatal exposure to cimetidine results in gonadal and sexual dysfunction in adult males. Science 1982;21:4934.
6. Parker S, Udani M, Gavaler JS, Van Thiel DH. Pre- and neonatal exposure to cimetidine but not ranitidine adversely affects adult sexual functioning of male rats. Neurobehav Toxicol Teratol 1984;6:3138.
7. Parker S, Schade RR, Pohl CR, Gavaler JS, Van Thiel DH. Prenatal and neonatal exposure of male rat pups to cimetidine but not ranitidine adversely affects subsequent adult sexual functioning. Gastroenterology 1984;86:67580.
8. Walker TF, Bott JH, Bond BC. Cimetidine does not demasculinize male rat offspring exposed in utero. Fundam Appl Toxicol 1987;8:18897.
9. Shapiro BH, Hirst SA, Babalola GO, Bitar MS. Prospective study on the sexual development of male and female rats perinatally exposed to maternally administered cimetidine. Toxicol Letters 1988;44:31529.
10. Dicke JM, Johnson RF, Henderson GI, Kuehl TJ, Schenker S. A comparative evaluation of the transport of H2-receptor antagonists by the human and baboon placenta. Am J Med Sci 1988;295:198206.
11. Schenker S, Dicke J, Johnson RF, Mor LL, Henderson GI. Human placental transport of cimetidine. J Clin Invest 1987;80:142834.
12. Howe JP, McGowan WAW, Moore J, McCaughey W, Dundee JW. The placental transfer of cimetidine. Anaesthesia 1981;36:3715.
13. McGowan WAW. Safety of cimetidine in obstetric patients. J R Soc Med 1979;72:9027.
14. Johnston JR, Moore J, McCaughey W, Dundee JW, Howard PJ, Toner W, McClean E. Use of cimetidine as an oral antacid in obstetric anesthesia. Anesth Analg 1983;62:7206.
15. Knott PD, Thorpe SS, Lamont CAR. Congenital renal dysgenesis possibly due to captopril. Lancet 1989;1:451.
16. Corazza GR, Gasbarrini G, Di Nisio Q, Zulli P. Cimetidine (Tagamet) in peptic ulcer therapy during pregnancy: a report of three cases. Clin Trials J 1982;19:913.
17. Glade G, Saccar CL, Pereira GR. Cimetidine in pregnancy: apparent transient liver impairment in the newborn. Am J Dis Child 1980;134:878.
18. Zulli P, DiNisio Q. Cimetidine treatment during pregnancy. Lancet 1978;2:9456.
19. Husemeyer RP, Davenport HT. Prophylaxis for Mendelson's syndrome before elective caesarean sections. A comparison of cimetidine and magnesium trisilicate mixture regimens. Br J Obstet Gynaecol 1980;87:56570.
20. Pickering BG,, Palahniuk RJ, Cumming M. Cimetidine premedication in elective caesarean section. Can Anaesth Soc J 1980;27:335.
21. Dundee JW, Moore J, Johnston JR, McCaughey W. Cimetidine and obstetric anaesthesia. Lancet 1981;2:252.
22. McCaughey W, Howe JP, Moore J, Dundee JW. Cimetidine in elective caesarean section. Effect on gastric acidity. Anaesthesia 1981;36:16772.
23. Crawford JS. Cimetidine in elective caesarean section. Anaesthesia 1981;36:6412.
24. McCaughey W, Howe JP, Moore J, Dundee JW. Cimetidine in elective caesarean section. Anaesthesia 1981;36:642.
25. Hodgkinson R, Glassenberg R, Joyce TH III, Coombs DW, Ostheimer GW, Gibbs CP. Safety and efficacy of cimetidine and antacid in reducing gastric acidity before elective cesarean section. Anesthesiology 1982;57:A408.
26. Ostheimer GW, Morrison JA, Lavoie C, Sepkoski C, Hoffman J, Datta S. The effect of cimetidine on mother, newborn and neonatal neurobehavior. Anesthesiology 1982;57:A405.
27. Hodgkinson R, Glassenberg R, Joyce TH III, Coombs DW, Ostheimer GW, Gibbs CP. Comparison of cimetidine (Tagamet) with antacid for safety and effectiveness in reducing gastric acidity before elective cesarean section. Anesthesiology 1983;59:8690.
28. Qvist N, Storm K. Cimethidine pre-anesthetic: a prophylactic method against Mendelson's syndrome in cesarean section. Acta Obstet Gynecol Scand 1983;62:1579.
29. Okasha AS, Motaweh MM, Bali A. Cimetidine-antacid combination as premedication for elective caesarean section. Can Anaesth Soc J 1983;30:5937.
30. Frank M, Evans M, Flynn P, Aun C. Comparison of the prophylactic use of magnesium trisilicate mixture B.P.C., sodium citrate mixture or cimetidine in obstetrics. Br J Anaesth 1984;56:35562.
31. McAuley DM, Halliday HL, Johnston JR, Moore J, Dundee JW. Cimetidine in labour: absence of adverse effect on the high-risk fetus. Br J Obstet Gynaecol 1985;92:3505.
32. Johnston JR, McCaughey W, Moore J, Dundee JW. Cimetidine as an oral antacid before elective caesarean section. Anaesthesia 1982;37:2632.
33. Johnston JR, McCaughey W, Moore J, Dundee JW. A field trial of cimetidine as the sole oral antacid in obstetric anaesthesia. Anaesthesia 1982;37:338.
34. Thorburn J, Moir DD. Antacid therapy for emergency caesarean section. Anaesthesia 1987;42:3525.
35. Howe JP, Dundee JW, Moore J, McCaughey W. Cimetidine: Has it a place in obstetric anaesthesia? Anaesthesia 1980;35:4212.
36. Kallen B. Delivery outcome after the use of acid-suppressing drugs in early pregnancy with special Reference to omeprazole. Br J Obstet Gynaecol 1998;105:87781.
37. Ruigomez A, Rodriguez LAG, Cattaruzzi C, Troncon MG, Agostinis L, Wallander MA, Johansson S. Use of cimetidine, omeprazole, and ranitidine in pregnant women and pregnancy outcomes. Am J Epidemiol 1999;150:47681.
38. Smallwood RA, Berlin RG, Castagnoli N, Festen HPM, Hawkey CJ, Lam SK, Langman MJS, Lundborg P, Parkinson A. Safety of acid-suppressing drugs. Dig Dis Sci 1995;40(Suppl):63S80S.
39. Kwanashie HO, Osuide G, Wambebe C, Ikediobi CO. Effects of maternally administered cimetidine during lactation on the development of drug metabolizing enzymes in mouse pups. Biochem Pharmacol 1989;38:2046.
40. Somogyi A, Gugler R. Cimetidine excretion into breast milk. Br J Clin Pharmacol 1979;7:6279.
41. Oo CY, Kuhn RJ, Desai N, McNamara PJ. Active transport of cimetidine into human milk. Clin Pharmacol Ther 1995;58:54855.
42. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.
    
    

Questions and Answers

Is it ok to take Cimetidine heartburn acid reducer pills with alcohol?, Is it ok to take Cimetidine tablets which are heartburn relief pills you get at the store with alcohol?

Might be defeating the point? You have heartburn from '?' so you want to take the remedy and then drink alcohol which might be causing the heartburn? Like banging your head off a brick wall, then taking a single aspirin, then banging your head off the brick wall again? Best of Luck

I suffer from ulcers ,what risk do i stand if i continue taking cimetidine for more than a year?, For 7 years now i have`nt find treatment for gastric ulcers but now i only get a relief when i take cimetidine twice a day, one in the morning and one at bed time. please help!

Has your doctor checked you for the H. Pyloric Bacterium?
The bacterium is shaped like a corkscrew, and can indeed insert itself right into the lining of your stomach and live there for years, causing ulcers. It does no good to take cimetidine or prilosec, for as long as the bacterium is there, the ulcers will come back. If your doctor does a blood test and finds the H. Pyloric Bacterium, he will put you on two weeks of an oral antibiotic to kill the bacterium. then he can put you on Nexium or over the counter Prilosec until the ulcers heal completely up. Now be warned, if you have the bacterium, seven years is a long time and you may require longer than two weeks, you should take the antibiotics the required two weeks and then be checked again to make sure the germ is completely gone.

How is Cimetidine (tagamet) and Famotidine (pepcid) different?, How do they work differently through the body. If it does the same thing how can they sell as two different compounds? Please cite your refferences. Thanks alot!

Close, but they block the H2 receptor, not H1. They are two different compunds or the same class that block histamine induced acid secretion.

Has anyone ever been on Cimetidine (aka Tagamet) to help get rid of flat warts? How did it work for you?, My podiatrist just put me on this medicine, and I was wondering if it really works all that well or if I should tell her to stuff it because of the long list of potential drug reactions and side effects. Today is my first day of the medicine; she's got me on 400mg 3x a day. Thanks for your input!

I've prescribed it before for other folks as an adjunct (not the only) medicine for wart therapy. I found it didn't work so well on its own...

As far as the side effects go, any medicine you take has a laundry list of potential side effects. If you feel fine on the medicine, it won't hurt to continue on it. Tagamet is a safe medicine in most people. My suggestion would be to simply buy some Compund W and use it along with the Tagamet.

What is the difference between Tagamet (Cimetidine) and Pepcid (Famotidine)?,

Both drugs are H2-receptor antagonists, thus, both inhibit acid production in the stomach.

They are usually prescribed for GERD, but neither drug treats the cause of GERD.

Both drugs are dangerous. They cause malabsorption of some vitamins (e.g. Vitamin B12) and many minerals (e.g. calcium, zinc, iron, etc.).

These drugs also cause bacterial overgrowth in the small intestine, which is not a good thing! In fact, when researchers want to study bacterial overgrowth, they induce it with these types of drugs!

In conclusion: avoid these drugs. Find a doctor that will work with you to 'find and fix' the cause of your problem.

what effect does cimetidine (tagamet) have on opiate levels in a urine test?, what effect does cimetidine (tagamet) have on opiate levels in a urine test?

It should have no effect.

Can I take "Cimetidine 400MG" for a sinus infection?, A while ago I had a viral infection on my foot from playing soccer..I still have some left over because it cleaned up before the medication ran out.

NOW I have a sinus infection, It says on the bottle:

TAKE ONE TABLET BY MOUTH THREE TIMES DAILY FOR VIRAL INFECTION

Will this cure my sinus infection?

Thank you soooo much!

I had no idea that Tagamet could be used to treat viral infections. It is sold over the counter for GERD.

Although a sinus affliction may have been brought on by virus, doubtful the infection is viral but rather bacterial and would more than likely not respond to an antiviral medication.

As a nurse, I would say no. But as a consumer, I would say why not try it.....you have nothing to lose.

Can also try a Netty Pot, which rinses the infection out of the sinuses. And do take an antihistamine to help dry out sinuses. I also breathe steam from a pot boiling on the stove. This will help to loosen mucous accumulated in the sinuses.

I was told by a doctor many years ago in response to a sinus infection, to take a little salt water, put it in the palm of your hand, and plug one nostril. Use the other nostril to snort up the salt water in the palm, then blow it back out (over the sink). Repeat with other nostril. do this several times, and repeat several times a day. This will also help to rinse nostrils, but not as good as the Netty Pot.

Hope you feel better.....

what is the different b/w ZANTAC ( Ranitidine ) & Tagamet (cimetidine ) ?,

Cimetidine (Tagamet) and ranitidine (Zantac) belong to the same class of acid suppressing agents called histamine receptor antagonists and if given in equal doses work equivalently. On the other hand, omeperazole (Prilosec) and lansoprazole (Prevacid) are proton pump inhibitors and are very potent inhibitors of acid secretion. Most physicians will initially try cimetidine or ranitidine prior to considering the more costly proton pump inhibitors. Patients whose symptoms do not respond to histamine receptor antagonists will often obtain relief with proton pump inhibitors. In clinical trials where patients with erosive esophagitis and peptic ulcer disease are studied, patients report better symptom relief with proton pump inhibitors. Furthermore, faster healing rates are also seen with proton pump inhibitors. I hope you find this information helpful.