Tramadol

 Risk Factor: CM
 Class: CENTRAL NERVOUS SYSTEM DRUGS / Central Analgesics

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

Tramadol is a synthetic, centrally acting, analgesic analogue of codeine that has the potential to cause physical dependence similar to, but much less, than that produced by opiates. Because of its low addiction potential, tramadol is not classified as a controlled substance. The drug is available only as an oral tablet in the United States but has been used both parenterally and rectally in other countries.

Oral doses up to 50 mg/kg in male rats and 75 mg/kg in female rats had no effects on fertility (1). Reproductive studies, conducted with tramadol in mice (120 mg/kg), rats (25 mg/kg or higher), and rabbits (75 mg/kg or higher), showed embryotoxic and fetotoxic effects at maternally toxic doses, 315 times the maximum human dose or higher, but no fetal toxicity was observed with lower doses that were not maternally toxic (1). No teratogenic effects were observed with any of the doses. The observed toxicity consisted of decreased fetal weights, skeletal ossification, and increased supernumerary ribs. Transient delays in developmental or behavioral parameters were seen in rat pups.

Shepard described a reproductive study using oral and SC tramadol in mice, at doses up to 120 mg/kg, and in rats, at doses up to 60 mg/kg, that observed no teratogenic effects (2). Schardein also cited the same study (3).

Tramadol has a molecular weight of approximately 300 and crosses the placenta to the fetus. In 40 women given 100 mg of tramadol during labor, the mean ratio of drug concentrations in the umbilical cord and maternal serum was 0.83 (4).

Several studies outside of the United States, some of which were reviewed in 1993 (5) and 1997 publications (4), have compared the use of tramadol with meperidine or morphine for labor analgesia (6,7,8,9,10,11 and 12). In five of these studies (6,7,8,9 and 10), the use of tramadol was associated with less neonatal respiratory depression than meperidine, but no difference was observed in two studies in comparison with meperidine or morphine (11,12). In one of these latter studies, no differences in maternal response, adverse effects, or newborn condition were observed between tramadol, meperidine, and morphine (11). In the other study, tramadol and meperidine were combined with triflupromazine, a phenothiazine tranquilizer added in an attempt to reduce the emetic effects of the analgesics, and compared with tramadol alone (12). No decrease or difference between the three groups in the incidence and severity of the side effects was observed.

The effects of tramadol and meperidine, 100 mg IV for each drug, were compared in laboring patients in a study conducted in Thailand (9). A second or third dose of 50 mg IV was given at 30-minute intervals if requested. A significant increase in the incidence of neonatal respiratory depression was observed in the offspring of the meperidine group, if delivery occurred 24 hours after the last dose. The respiratory depressant effects of meperidine are known to be time- and dose-related, increasing markedly after 60 minutes (see Meperidine).

A study from Singapore found that 100 mg IM of tramadol was equivalent in analgesic effect to 75 mg IM of meperidine for the control of labor pain (10). Meperidine was associated with a significantly higher frequency of adverse effects (nausea, vomiting, fatigue, drowsiness, and dizziness) in the mothers and a significantly lower respiratory rate in the newborns. However, the injection-delivery interval in the patients was 78 hours.

In a 1997 case report, a male infant developed withdrawal symptoms between 24 and 48 hours after birth (13). Symptoms consisted of trembling, tachypnea, tachycardia, hypertonic muscle tone, signs of tetany when touched, and a single mild convulsion. The mother admitted to taking tramadol 300 mg/day for 4 years. The infant was treated with diazepam and/or phenobarbital for 13 days until the symptoms had fully resolved. No long-term follow-up of the infant was reported. The authors concluded that the estimated elimination half-life of 36 hours was consistent with the course of the withdrawal syndrome (13).

Only the one report above has described the use of tramadol early in human gestation and an assessment of the risk, if any, that the drug presents to the embryo and fetus cannot be determined. Based on that case, neonatal withdrawal is a potential complication after continuous use in the mother. Because dose-related embryo and fetal toxicity have been observed in animals, use of tramadol during early human gestation should probably be avoided until additional data are available. Moreover, the delays in development and behavior observed in newborn rats appear to lessen any clinically significant advantage the drug may have over traditional narcotic analgesics.

Breast Feeding Summary

Both tramadol and its pharmacologic active metabolite are excreted into human milk (1). After a single 100-mg IV dose, the cumulative amounts of the parent drug and metabolite excreted into milk within 16 hours were 100 and 27 g, respectively (1). The recommended dose of tramadol is 50100 mg every 46 hours up to a maximum of 400 mg/day. Moreover, the mean absolute bioavailability of a 100-mg oral dose is 75%. Thus, ingestion of the recommended dose may produce drug amounts in breast milk that could exceed those reported above. The effects of this exposure on a nursing infant are unknown.

References

1. Product information. Ultram. McNeil Pharmaceutical, 1997.
2. Yamamoto H, Kuchii M, Hayano T, Nishino H. A study on teratogenicity of both CG-315 and morphine in mice and rats. Oyo Yakuri 1972;6:105569. As cited in Shepard TH. Catalog of Teratogenic Agents. 8th ed. Baltimore, MD: Johns Hopkins University Press, 1995:420.
3. Yamamoto H, Kuchii M, Hayano T, Nishino H. Teratogenicity of the new central analgesic 1-(m-methoxyphenyl)-2-(dimethylaminomethyl)cyclohexanol hydrochloride (Cg-315) in mice and rats. Oyo Yakuri 1972;6:105569. As cited in Schardein JL. Chemically Induced Birth Defects. 2nd ed. New York: Marcel Dekker, 1993:133.
4. Lewis KS, Han NH. Tramadol: a new centrally acting analgesic. Am J Health-Syst Pharm 1997;54:64352.
5. Lee CR, McTavish D, Sorkin EM. Tramadol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in acute and chronic pain states. Drugs 1993;46:31340.
6. Husslein P, Kubista E, Egarter C. Obstetrical analgesia with tramadolresults of a prospective randomized comparative study with pethidine. Z Geburtshilfe Perinatol 1987;191:2347.
7. Bitsch M, Emmrich J, Hary J, Lippach G, Rindt W. Obstetrical analgesia with tramadol. Fortschr Med 1980;98:6324.
8. Bredow V. Use of tramadol versus pethidine versus denaverine suppositories in labora contribution to noninvasive therapy of labor pain. Zentralbl Gynakol 1992;114:5514.
9. Suvonnakote T, Thitadilok W, Atisook R. Pain relief during labour. J Med Assoc Thailand 1986;69:57580.
10. Viegas OAC, Khaw B, Ratnam SS. Tramadol in labour pain in primiparous patients. A prospective comparative clinical trial. Eur J Obstet Gynecol Reprod Biol 1993;49:1315.
11. Prasertsawat PO, Herabutya Y, Chaturachinda K. Obstetric analgesia: comparison between tramadol, morphine, and pethidine. Curr Ther Res Clin Exp 1986;40:10228.
12. Kainz C, Joura E, Obwegeser R, Plockinger B, Gruber W. Effectiveness and tolerance of tramadol with or without an antiemetic and pethidine in obstetric analgesia. Z Geburtshilfe Perinatol 1992;196:7882.
13. Meyer FP, Rimasch H, Blaha B, Banditt P. Tramadol withdrawal in a neonate. Eur J Clin Pharmacol 1997;53:15960.
    
    

Questions and Answers

Is it ok to still take Tramadol when pregnant?

Has anyone taken pain medication when pregnant? I have been on tramadol for 2 years now and Ive just found out I am 5 weeks pregnant. If I stop taking the meds I get extreme withdrawel symptoms. I can't go to my GP because he thinks I have come off them after treating me for the addiction. Does anyone know of any effects this might have on the baby? Im really worried.

You'd better go see an OB/GYN and be honest with him. Better you admit you are addicted to the pain meds than go through the entire pregnancy and then have to deal with the consequences.

Tramadol (Ultram) is Pregnancy Category C drug which means during animal testing the drugs did negatively affect the fetus, however, testing has not been done on humans. So category C drugs aren't used unless they are medically necessary and another drug cannot be substituted.

Let your doctor know you want to have a healthy baby and you want to quit. Your doctor may be mad but he'll be a hell of a lot more mad later if you don't tell him. Do what you have to do. Most likely you will be weaned off the pills slowly and another drug may be given to help ease the withdrawal symptoms. You can do it.!

Tramadol and pregnancy. anyone take this while pregnant? Any more info than what the internet has to offer?

I am 12 weeks pregnant. I haven't been taking tramadol much at all, howver the last 3 days I have taken about 3 x per day. I have back pain and something was needed. Is there anyone who knows more about this issue, or has been thru this themselves? What was the outcome? Is there Birth defects involved?

There are no adequate and well controlled studies examining tramadol in pregnant women, therefore tramadol should not be used during pregnancy. Tramadol has been shown to be embryotoxic and fetotoxic in mice. The effect of tramadol, if any, on the later growth, development and functional maturation of the child is unknown.

Seeing as you have been taking tramadol only in the last 3 days it cant be for sure that you have caused any damage but I would say its unlikely that you have caused any damage to your baby. However you need to STOP taking tramadol immediately and consult your doctor for alternative pain medication as soon as possible. Don't stress! I understand back pain, particularly during a pregnancy, you had to do some something to relieve the pain but because the effects of tramadol in pregnancy aren't known its safest not to use it and ask the doctor for something else. Good Luck :)

Tramadol withdrawal while pregnant?

My sister is 29 and just found out days ago that she is pregnant (probably 6 weeks along). She had been told she wouldn't be able to have babies, so she was never worried about that. She also takes Tramadol, on a high dose, for chronic pain. She stopped the minute she took the pregnancy test, but she is now going through withdrawal and is MISERABLE. I just think that this misery is not good for the baby, so what's worse: stopping cold turkey and going through days, and possibly weeks, of agony or to slowly cut down on her dosage until she's able to be off the meds without the extreme side effects?

She is so embarrased that she won't call her doctor (the one who prescribed her the pain meds) and doesn't want to tell her OBGYN, and I can't do anything about it.

Help!!!

She shouldn't be embarrassed, she really needs to speak with a physician. This could be jeopardizing her baby's health and no one here is really qualified to tell her what she should do.

Stopped Long Term Use of Codeine, Now Taking Tramadol and 11 weeks pregnant is it really dangerous?

When I was taking the codeine I didn't know I was pregnant and when I did find out I actually stopped the use, but I feel that I am addicted and started taking tramadol. I can't stop it and I'm very depressed if it will be harmful to my baby. In addition to the codeine which I took short term when I first found out I was pregnant, I was taking Ativan since I have anxiety issues before I completely stopped that too. It's the result of a serious automobile accident that almost killed me.

Get into detox. Consider Subutex or Suboxone. Make sure your OB and your pain management docs know your situation.

Pregnant and addicted to Tramadol...?

I have been adicted to Tramadol for about 4 or 5 years now. I have never taken large doses. Most of these years I have taken no more than 200mg daily. (Usually 2 in the morning and 1 or 1&1/2 in the afternoon, 50mg pills) I found out a few days ago I am pregnant (about 5 weeks) and I am trying to stop taking these pills since I know it can't be good for me or the baby! It is so hard to stop! I am super weak, its hard to breathe, my whole body hurts, I have had a migraine for 3 days... the list goes on.. I have a full time job and I really can't imagine feeling like this at work tomorrow! I can't think straight! Any suggestions?

You need to talk to your doctor. According to Drugs.com, you're not supposed to quit cold turkey unless a doctor tells you to. You're probably going to need an addiction counseling program.
The thing is you should not delay. Beg, plead, do whatever it takes, but get into see your doctor tomorrow. You can call in sick to work. It won't be a lie, because addiction is a sickness.
I'll pray for you and your unborn child.

When pregnant is it ok to take painkillers?

Hi just wondering if it is ok to take Tramadol Painkillers when pregnant as my doctor said it was ok but i had a miscarrage i take these because i suffer very bad with kidney infections, If im trying again would you wreckamend to take these painkillers.

Of course you aren't supposed to take anything stronger than acetaminophen UNLESS your doctor prescribes it. Contrary to popular belief, many prescription pain relievers - even those containing narcotics like Vicodin, Percocet, etc. - are safe when taken as prescribed and not used chronically throughout the pregnancy.

Obviously your prescribing doc knew you were pregnant. While their are risks with just about every medication you take during pregnancy, most of the time the risk is extremely slight, and when you weight that small risk vs. the benefits you receive from taking them it makes it worth it that teeny-tiny risk.

Please talk to your doctor more about your medication if you still have questions. There are a lot of medications that list in the warnings that they should not be taken by pregnant women *unless directed by a physician. Most of the time these meds still are safe to take despite the official warnings on the label.

I am 7 months pregnant and have started to take,Tramadol. Is this harmful to the baby from this point on?

If it came from your OB then he obviously felt that this narcotic wouldnt affect the baby...I have faith that he took every pro and con into consideration prior to giving this to you.