Mercaptopurine

 Risk Factor: DM
 Class: ANTINEOPLASTICS

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

Mercaptopurine (6-MP) is an antimetabolite antineoplastic agent. References citing the use of mercaptopurine in 79 human pregnancies have been located, including 34 cases in which the drug was used in the 1st trimester (1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20 and 21). Excluding those pregnancies that ended in abortion or stillbirths, congenital abnormalities were observed in only one infant (10). Defects noted in the infant were cleft palate, microphthalmia, hypoplasia of the ovaries and thyroid gland, corneal opacity, cytomegaly, and intrauterine growth retardation. The anomalies were attributed to busulfan.

Neonatal toxicity as a result of combination chemotherapy has been observed in three infants: pancytopenia (6), microangiopathic hemolytic anemia (9), and transient severe bone marrow hypoplasia (12). In the latter case, administration of mercaptopurine was stopped 3.5 weeks before delivery because of severe maternal myelosuppression. No chemotherapy was given during this period, and her peripheral blood counts were normal during the final 2 weeks of her pregnancy (12).

In another case, a 34-year-old woman with acute lymphoblastic leukemia was treated with multiple antineoplastic agents from 22 weeks' gestation until delivery of a healthy female infant 18 weeks later (14). Mercaptopurine was administered throughout the 3rd trimester. Chromosomal analysis of the newborn revealed a normal karyotype (46,XX) but with gaps and a ring chromosome. The clinical significance of these findings is unknown, but since these abnormalities may persist for several years, the potential existed for an increased risk of cancer, as well as for a risk of genetic damage in the next generation (14).

Data from one review indicated that 40% of the infants exposed to anticancer drugs were of low birth weight (2). This finding was not related to the timing of exposure. In addition, except in a few cases, long-term studies of growth and mental development in infants exposed to mercaptopurine during the 2nd trimester, the period of neuroblast multiplication, have not been conducted (22). However, growth and development were normal in 13 infants (one set of twins) examined for 6 months to 10 years (12,15,16,18,19,20 and 21).

Severe oligospermia has been described in a 22-year-old male receiving sequential chemotherapy of cyclophosphamide, methotrexate, and mercaptopurine for leukemia (23). After treatment was stopped, the sperm count returned to normal and the patient fathered a healthy female child. Others have also observed reversible testicular dysfunction (24).

Ovarian function in females exposed to mercaptopurine does not seem to be affected adversely (25,26,27,28 and 29). An investigator noted in 1980 that long-term analysis of human reproduction following mercaptopurine therapy had not been reported (30). However, a brief 1979 correspondence described the reproductive performance of 314 women after treatment of gestational trophoblastic tumors, 159 of whom had conceived with a total of 218 pregnancies (28). Excluding the 17 women still pregnant at the time of the report, 38 (79%) of 48 women exposed to mercaptopurine as part of their therapy delivered live, term infants. A more detailed report of these and additional patients was published in 1984 (31). This latter study, and another published in 1988 (32), both involving women treated for gestational trophoblastic neoplasms, are discussed below.

In 436 long-term survivors treated with chemotherapy between 1958 and 1978, 95 (22%) received mercaptopurine as part of their treatment regimens (31). Of the 95 women, 33 (35%) had at least one live birth (numbers given in parentheses refer to mean/maximum mercaptopurine dose in grams) (5.9/30.0), 3 (3%) conceived but had no live births (5.3/14.0), 3 (3%) failed to conceive (1.3/2.0), and 56 (59%) did not try to conceive (5.4/30.0). Additional details, including congenital anomalies observed, are described in the monograph for methotrexate (see Methotrexate).

A 1988 report described the reproductive results of 265 women who had been treated from 1959 to 1980 for gestational trophoblastic disease (32). Single-agent chemotherapy was administered to 91 women, including 26 cases in which mercaptopurine was the only agent used, whereas sequential (single-agent) and combination therapy was administered to 67 and 107 women, respectively. Of the total group, 241 were exposed to pregnancy and 205 (85%) of these women conceived, with a total of 355 pregnancies. The time interval between recovery and pregnancy was 1 year or less (8.5%), 12 years (32.1%), 24 years (32.4%), 46 years (15.5%), 68 years (7.3%), 810 years (1.4%), and more than 10 years (2.8%). A total of 303 (4 sets of twins) liveborn infants resulted from the 355 pregnancies, 3 of whom had congenital malformations: anencephaly, hydrocephalus, and congenital heart disease (1 in each case). No gross developmental abnormalities were observed in the dead fetuses. Cytogenetic studies were conducted on the peripheral lymphocytes of 94 children and no significant chromosomal abnormalities were noted. Moreover, follow-up of the children, with more than 80% of the group older than 5 years of age (the oldest was 25 years), revealed normal development. The reproductive histories and pregnancy outcomes of the treated women were comparable to those of the normal population (32).

Occupational exposure of the mother to antineoplastic agents during pregnancy may present a risk to the fetus. A position statement from the National Study Commission on Cytotoxic Exposure and a research article involving some antineoplastic agents are presented in the monograph for cyclophosphamide (see Cyclophosphamide).

Breast Feeding Summary

No reports describing the use of mercaptopurine during lactation have been located. Because of the relatively low molecular weight (about 170), transfer into milk should be expected. Because of the potential for severe toxicity in the nursing infant, women receiving this antineoplastic agent should not breast feed.

References

1. Moloney WC. Management of leukemia in pregnancy. Ann NY Acad Sci 1964;114:85767.
2. Nicholson HO. Cytotoxic drugs in pregnancy: review of reported cases. J Obstet Gynaecol Br Commonw 1968;75:30712.
3. Gililland J, Weinstein L. The effects of cancer chemotherapeutic agents on the developing fetus. Obstet Gynecol Surv 1983;38:613.
4. Wegelius R. Successful pregnancy in acute leukaemia, Lancet 1975;2:1301.
5. Nicholson HO. Leukaemia and pregnancy: a report of five cases and discussion of management. J Obstet Gynaecol Br Commonw 1968;75:51720.
6. Pizzuto J, Aviles A, Noriega L, Niz J, Morales M, Romero F. Treatment of acute leukemia during pregnancy: presentation of nine cases. Cancer Treat Rep 1980;64:67983.
7. Burnier AM. Discussion. In Plows CW. Acute myelomonocytic leukemia in pregnancy: report of a case. Am J Obstet Gynecol 1982;143:413.
8. Dara P, Slater LM, Armentrout SA. Successful pregnancy during chemotherapy for acute leukemia. Cancer 1981;47:8456.
9. McConnell JF, Bhoola R. A neonatal complication of maternal leukemia treated with 6-mercaptopurine. Postgrad Med J 1973;49:2113.
10. Diamond J, Anderson MM, McCreadie SR. Transplacental transmission of busulfan (Myleran) in a mother with leukemia: production of fetal malformation and cytomegaly. Pediatrics 1960;25:8590.
11. Khurshid M, Saleem M. Acute leukaemia in pregnancy. Lancet 1978;2:5345.
12. Okun DB, Groncy PK, Sieger L, Tanaka KR. Acute leukemia in pregnancy: transient neonatal myelosuppression after combination chemotherapy in the mother. Med Pediatr Oncol 1979;7:3159.
13. Doney KC, Kraemer KG, Shepard TH. Combination chemotherapy for acute myelocytic leukemia during pregnancy: three case reports. Cancer Treat Rep 1979;63:36971.
14. Schleuning M, Clemm C. Chromosomal aberrations in a newborn whose mother received cytotoxic treatment during pregnancy. N Engl J Med 1987;317:16667.
15. Turchi JJ, Villasis C. Anthracyclines in the treatment of malignancy in pregnancy. Cancer 1988;61:43540.
16. Feliu J, Juarez S, Ordonez A, Garcia-Paredes ML, Gonzalez-Baron M, Montero JM. Acute leukemia and pregnancy. Cancer 1988;61:5804.
17. Haerr RW, Pratt AT. Multiagent chemotherapy for sarcoma diagnosed during pregnancy. Cancer 1985;56:102833.
18. Frenkel EP, Meyers MC. Acute leukemia and pregnancy. Ann Intern Med 1960;53:65671.
19. Loyd HO. Acute leukemia complicated by pregnancy. JAMA 1961;178:11403.
20. Lee RA, Johnson CE, Hanlon DG. Leukemia during pregnancy. Am J Obstet Gynecol 1962;84:4558.
21. Coopland AT, Friesen WJ, Galbraith PA. Acute leukemia in pregnancy. Am J Obstet Gynecol 1969;105:12889.
22. Dobbing J. Pregnancy and leukaemia. Lancet 1977;1:1155.
23. Hinkes E, Plotkin D. Reversible drug-induced sterility in a patient with acute leukemia. JAMA 1973;223:14901.
24. Lendon M, Palmer MK, Hann IM, Shalet SM, Jones PHM. Testicular histology after combination chemotherapy in childhood for acute lymphoblastic leukaemia. Lancet 1978;2:43941.
25. Schilsky RL, Lewis BJ, Sherins RJ, Young RC. Gonadal dysfunction in patients receiving chemotherapy for cancer. Ann Intern Med 1980;93:10914.
26. Gasser C. Long-term survival (cures) in childhood acute leukemia. Paediatrician 1980;9:34457.
27. Bacon C, Kernahan J. Successful pregnancy in acute leukaemia. Lancet 1975;2:515.
28. Walden PAM, Bagshawe KD. Pregnancies after chemotherapy for gestational trophoblastic tumours. Lancet 1979;2:1241.
29. Sanz MH, Rafecas FJ. Successful pregnancy during chemotherapy for acute promyelocytic leukemia. N Engl J Med 1982;306:939.
30. Steckman ML. Treatment of Crohn's disease with 6-mercaptopurine: what effects on fertility? N Engl J Med 1980;303:817.
31. Rustin GJS, Booth M, Dent J, Salt S, Rustin F, Bagshawe KD. Pregnancy after cytotoxic chemotherapy for gestational trophoblastic tumours. Br Med J 1984;288:1036.
32. Song H, Wu P, Wang Y, Yang X, Dong S. Pregnancy outcomes after successful chemotherapy for choriocarcinoma and invasive mole: long-term follow-up. Am J Obstet Gynecol 1988;158:53845.
    
    

Questions and Answers

Can mercaptopurine (6-mp) treatment cause an increased number of moles?, Or is it more likely the decresed resistence to uv light?

These are the only side effects i know of, but you can always ask your doctor:


Common side effects
Many people have one or more of the following side effects

Fatigue - for many people this is the most troublesome side effect of all. Tiredness often carries on after treatment has ended. Most people find their energy levels are back to normal from 6 months to a year after their treatment finishes.
Temporary effect on the bone marrow. The bone marrow makes blood cells and a drop in its function can cause

- An increased risk of getting infections. This is due to a temporary drop in the number of white blood cells produced by the bone marrow. Having a low white blood count means that you are less able to fight infections and can become very ill. You may have headaches, aching muscles, a cough, sore throat, pain passing urine or feel cold and shivery. Infections can sometimes be life threatening. You should contact your doctor urgently if you think you have an infection.

- Tiredness and breathlessness. This is due to a drop in the number of red blood cells made by your bone marrow which is called anaemia. You may need a blood transfusion to treat anaemia.

- Getting bruises more easily. This is due to a drop in the number of platelets produced by your bone marrow. You may have lots of tiny red spots or bruises on your arms or legs. You may have nosebleeds or notice your gums bleed when you brush your teeth.

Contact your hospital if you have any of these bone marrow side effects.


Feeling or being sick is usually mild and easily controlled with anti sickness injections and tablets
Occasional Side Effects
Some people may have one or more of the following side effects


Diarrhoea - drink plenty of fluids and if it becomes severe or persistent tell your doctor or nurse – you could get dehydrated.
Sore mouth and throat
Liver problems – mercaptopurine can cause changes in your liver function. If you get this it usually starts 2 to 3 months after you begin treatment. And it will go back to normal when you stop treatment. If this happens you may notice your skin or the whites of your eye’s become yellow. Your doctor will take regular blood tests to check your liver function.
Loss of fertility - It is not known exactly what effect this drug may have on your fertility. It is important to talk with your doctor before starting treatment. Women may stop having periods (amenorrhoea). This may only be temporary.
Mercaptopurine may have a harmful effect on a developing baby. It is not advisable to breastfeed, become pregnant or father a child if you are having this drug. You should talk about contraception with your doctor before having the treatment.
An itchy rash
Rare side effects


Hair loss – this is rare. But if it does happen it usually begins 2 – 5 weeks after the treatment starts. Remember - this is only temporary. Your hair will grow back once treatment has finished.
Kidney problems - if this happens you may have swelling in your ankles and feet and lower back pain
Darkened skin on hands, feet or elbows, or red skin on radiotherapy treatment areas. It will go back to normal after treatment has finished.
Fever and chills
Remember

Not everyone will get these side effects. You may have none or several. A side effect may get worse through your course of treatment, or more side effects may develop as the course goes on. This depends on

- How many times you've had the drug before
- Your general health
- The amount of the drug you have (the dose)
- Other drugs you are having

Some side effects are inconvenient or upsetting but not damaging to your health
Some side effects are serious medical conditions and need treating. Where we have urged you to contact your doctor, this is because

- Your side effect may need treating
- Your drug dose may need reducing to try to prevent the side effect

Tell your doctor about any other medicines you are taking, including vitamins, herbal supplements and other over the counter remedies - some drugs can react together
Talk to your doctor, pharmacist or nurse about all your side effects so that they can help you manage them
People you can talk to about your side effects
Your chemotherapy nurse, clinic or ward nurse will have given you a contact number. You can ring if you have any questions or problems. They can give you advice or reassure you. If in doubt, call them.

this is the only skin reactions I found:

Skin rash, dry skin, itching, discoloration of the skin (hyperpigmentation) (uncommon) (see skin reactions).
Darkening of the skin where previous radiation treatment has been given. (radiation recall - see skin reactions) (rare).

Is it bad to drink alcohol if I'm taking asacol, mercaptopurine, prednisone, and celexa?,

Alcohol is a poison eliminated by your liver and excreted by your renal system.

Unfortunately, your liver also metabolizes drugs too. You should talk to a pharmacist or doctor and seek professional advice on these medications. Most of them will have a warning about alcohol use, if they interact.

Generally speaking, alcohol would not be recommended because the combination of drugs you are taking can get dangerous if alcohol intoxication is involved.

Does Mercaptopurine (aka Purinethol) interact with Ortho-Cyclen birth control?, And is it safe to take the Mercaptopurine in the morning and drink alcohol at night? (I am taking it for Lupus)

Mercaptopurine Oral
Back to Drug Overview
Thiopurines/Allopurinol; Oxypurinol

This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment.

Medical warning:

Serious. These medicines may interact and cause very harmful effects. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.

How the interaction occurs:

When these two medicines are taken together, your body may not process thiopurines properly.

What might happen:

The blood levels of your thiopurine may increase and cause toxic effects such as fever, chills, easy bruising or bleeding, black or tarry stools, blood in urine, or mouth or lip sores.

What you should do about this interaction:

Contact your healthcare professionals (e.g. doctor or pharmacist) as soon as possible about taking these two medicines together. They may already be aware of this drug interaction and may be monitoring you for it. If you develop any of the symptoms above, contact your doctor. It may be necessary to adjust the dose of your medicine. Do not start, stop, or change the dosage of any medicine before checking with them first.


no you should not be drinking with that type of medications

what are the side affects of mercaptopurine ?,

http://www.nlm.nih.gov/medlineplus/drugi...

has anyone taken mercaptopurine for joint pain?, If so was it effective? i am a 20 year old female that has ulcerative colitis and is otherwise in good health but for the past 8 months or so i have had joint pain related to the ulerative colitis, has anyone aver taken mercaptopurine for joint pain and was it effective? I have been offered other medications with crazy side effects and refused because of this ...please help!!!

No but ive taken Glucosamine Sulphate and it has been very effective. good luck and hope you get better!

what is the side effect of expired (purinethol -mercaptopurine tablets) thanks.?, expired purinethol

Bone marrow depression.

Is there a generic drug for Purinethol (Mercaptopurine)?, Where is the cheapest place to get it with a prescription if I will be paying for it out of pocket with no RX insurance benefit.

Mercaptopurine is the generic of Purinethol. It's very expensive, though. Your best bet is to call all of your local pharmacies and go with the one that has the best price.

I am on mercaptopurine for my Chrons. Is there any harm in my stopping taking it (because of side effects)?, I am 48, and have fairly sever Chron's. My doctor has had me on Asacol, and at times prednasone, but none of it has slowed down the Chrons. About 3 weeks ago, he started me on Mercaptopurine (Purinethol, or 6mp). I have not had any of the benefits yet, but have had very unpleasant side effects (loss of appetite & weight, stiffening of joints, and considerable shortness of breath). He suggested I stop the 6mp, at first I disagreed, thinking I wanted to give it a chance to work. But now I would like to stop - the only problem is I can't reach him for two more days. So I have not taken the medicine today, and just wonder if it is okay to simply stop taking the medicine, or if I should be doing/taking something else also.

Thank you.

You shouldn't have any problems stopping the medication. If you feel fine today after not taking, continue not taking it and when you can reach your doctor, tell him you have discontinued. Whatever you do, do not try to "catch up" on the doses, if you decide to take it. That can cause severe side effects including respiratory arrest.
Considering your side effects and the fact that the doctor has suggested stopping the medication, I think you'll be fine with not taking it.
Good luck finding a med. that works!

Are there any natural medicines that can cure ulcerative colitis?, 1,4000 mg a day of asacol. 100 mg a day of mercaptopurine. 1mg folic acid a day. 1 Multi-vitamin and 350mg iron per day. Keeps you stable. Does not stop the colon from bleeding. Anti inflammatory steroids good for short term, for long term very dangerous. Side effects are really nasty. Any natural medicines out there to be proven to cure ulcerative colitis or to help the colon stop bleeding completely? Please don't mention colectomy (removal of the colon). There has to be something before resorting to a last resort decision. Thank you.

I took asacol and it made my condition worse (more anemic) and I had the modified parks procedure (j-pouch) 3 years ago. I am much healthier and would do it all over again (surgery) if I had to. I was close to having a blood transfusion done and my colitis was so bad that they told me that I had a high chance of developing colon cancer in 10 yrs if I didn't have the whole colon removed. There is no colostomy bag and I lead a normal life (more than when I had U.C). There are support groups out there that can give you more insight and people who have had the procedure done (I still attend them)..I know you didn't want to know about this procedure but my ulcerative colitis was downright nasty and I tried to take the route of medicine.