Antineoplastics

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There are only a few ease reports on antineoplastics during lactation. The results of three reports on cisplatin are controversial: Egan (1985) could not detect cisplatin in breast milk, while de Vries (1989) found identical levels in milk and maternal blood. Ben-Baruch (1992) measured 10-fold lower concentrations in the milk compared to maternal plasma. Cyclophosphamide passes into mother's milk in large quantities, and thus acute toxic effects on the breastfed infant are possible. Relative dosages of under 5% have been reported for hydroxyurea, doxorubicin, and methotrexate (survey in Bennett 1996). A mother treated with etoposid for promyelocyte leukemia in remission initially had high levels in her milk, but there was no substance detectable 24 hours later. Concomitant mitoxantrone was measured at 129|ig/l in milk, and persisted in high concentrations 4 weeks later (Azuno 1995). There are no specific data on the other antineoplastics. This also applies to the mistletoe preparation viscum album.

Table 4.10.1 Antineoplastics during breastfeeding

Compound Indication Peak plasma time

Altretamlne Ovarian, breast, cervical, pancreatic 0.5-3.0 hours,

Anastrozole Suppresses estrogen, ovarian and breast cancers

Asparaginase Leukemia 14-24 hours

Bleomycin sulfate Cervical, Hodgklns and non-Hodgkins

Capecitabine Colon cancer

Carmustlne - BCNU Brain tumor, Hodgkins, gastric

Cetuximab

Chlorambucil Chronic leukemia, malignant lymphoma

Cisplatin Affinity for plasma proteins

4.10 Immunomodulating and antineoplastic agents

Half-life

Recommendation

4.7-10.5 hours 40-50 hours

39-49 hours

2-4 hours

0.5-0.75 hours, rapidly metabolized

70-100 hours

1-2 hours

Withhold breastfeeding for 72 hours

One dose, withhold breastfeeding for 10 days; if taken daily, lactation is contraindicated

Withhold breastfeeding for at least 7 days, total clearance = 50 x 5 = 250 hours ~ 10 days

Poor oral bioavailability, large molecular weight, withhold breastfeeding for 20 hours

Withhold breastfeeding for 6 hours

Withhold breastfeeding for at least 24 hours, especially if side effects are still present

55 days to dear, makes breastfeeding impractical

Withhold breastfeeding for 10 hours

58-90 hours Clearance is >56 days; follow platinum levels in milk or discontinue breastfeeding

('Continued)

Lactation

Table 4.10.1 {Continued)

Compound Indication

Cladribine Leukemia, multiple sderois

Cyclophosphamide Breast cancer

Peak plasma time

Cytusine arabinoside

Dactinomycin

Daunorubicin

Docetaxei Doxorubicin Epirubicin Erlotinib

Acute lymphoid leukemia

Wilm's lumor, Swing's sarcoma

Acute myelogenous and lymphocytic leukemies

Breast, lung, and bladder cancer

20% overall absorbed from Gl tract

Peak 24 hours Peak 4 hours

Etoposide

Exemestane

Testicular and lung cancers, bone marrow transplant

Fluorouracil

Actinic keratosis, breast cancer, colorectal cancer, condylomata acuminata

Clearance in 14 hours, withhold breastfeeding

Breastfed infants have had effects on their bone marrow; withhold breastfeeding for 48 hours

Withhold breastfeeding 15 hours

Withhold breastfeeding for at least 7 days

Withhold breastfeeding for a minimum of 7-10 days

Withhold breastfeeding for 48 hours

Withhold breastfeeding for at least 7 days

Withhold breastfeeding for at least 7 days

Withhold breastfeeding for a minimum of 7-10 days

Withhold breastfeeding for 24-36 hours

Discontinue breastfeeding if using multiple dosing; withhold for at least 5 days after last dose

Mothers receiving injections of 5-FU should withhold breastfeeding for a minimum ol 8 hours; mothers receiving topical therapy

Gemcitabine

Ifosfamide

Letrozole

Melphalan

Methotrexate

Mitomycin Mitoxantrone

Oxaliplatin Psditaxel

Metastatic breast cancer, non-small cell lung cancer, pancreatic cancer

Breast cancer

Estrogen-dependent tumors, Given daily for particularly breast cancer 2-6 weeks

Multiple myeloma, rhabdomyosarcoma, carcinoma of the ovary

Stomach, breast, pancreas Cancers and multiple sclerosis

Platinum compound

Kaposi's sarcoma, metastatic breast cancer

4.10 Immunomodulating and antineoplastic agents do not need to discontinue if the surface area is minimal

49 minutes (short infusions); 345-638 minutes (long infusions)

4-8 hours 2 days 15 hours

Withhold breastfeeding for a minimum of 6 hours with short infusion and 7 days for long infusions

Withhold breastfeeding for at least 48 hours

Long treatment period of weeks usually precludes breastfeeding

Withhold breastfeeding for 8 hours

8-15 hours Withhold breastfeeding for 4 days (96 hours)

23-78 minutes Withhold breastfeeding for 8 hours

23-215 hours, median Withhold breastfeeding for a minimum of

75 hours, still found 31 days in milk at 28 days

39 hours

27 hours

(Continued)

Lactation

Either test breast milk for platinum levels and don't use if levels are measurable, or permanently interrupt breastfeeding without measuring

Withhold breastfeeding for at least 6 days

Table 4.10.1 (Confirmed)

Compound Indication

Pentostatin Hairy cell leukemia

Tamoxifen Breast cancer

Teniposide Hematologic malignancies

Toremifene Binds estrogen receptors

Trastuzumab Metastatic breast cancer

Vinblastine Breast cancer, Kaposi's sarcoma,

Hodgkin's choriocarcinoma

Vincristine Breast cancer, Kaposi's sarcoma, non-Hodgkin's, lymphoma

Vinorelbine Advanced breast cancer, non-small cell lung cancer, non-Hodgkin's lymphoma, Hodgkin's disease, ovarian carcinoma

Peak plasma time Half-life

19-155 hours

3-18 hours (mean 5 7 hours)

Usually taken daily 3-21 days

5.4 hours 5 days

5.8 days

31.2-80 hours

Recommendation

Withhold breastfeeding for 4 days or longer if renal function is poor

Mothers receiving tamoxifen should not breastfeed

Withhold breastfeeding for 30-48 hours

Withhold breastfeeding for a minimum of 25-30 days

Low risk, but unknown; mothers should probably not breastfeed

Withhold breastfeeding for a minimum of 7 days

Withhold breastfeeding for a minimum of 35 days

Withhold breastfeeding for a minimum of 30 days

Information is obtained from multiple sources, including Hale 2006, Sweetman 2006, Briggs 2005

Recommendation. Table 4.10.1 lists many of these compounds, with an estimation of pump and discard times when appropriate. Others substances take so long to clear (4 weeks) that it is impractical to breastfeed. Some (such as tamoxifen) are given daily for long periods of time, so breastfeeding is not feasible.

References

Armenti VT, Radomski )S, Moritz. M) et al. Report from the national transplantation registry (NTPR): outcomes of pregnancy after transplantation. Clin Transpl 2003: 131-43.

Azuno Y. Kaku K. Fujita N. Mitoxantrone and etoposide in breast milk. Am I Hematol 1995; 48: 131-2.

Ben-Baruch G. Menczer |, Goshen R et al. Cisplatin excretion in human milk. J Natl Cancer Inst 1992; 84:451-2.

Bennett PN (ed.). Drugs and Human Lactation, 2nd edn Amsterdam: Elsevier, 1996.

Briggs. GG, Freeman KK, Yaffe S). Drugs in Pregnancy and Lactation, 7th edn. Philadelphia, PA: Llppincott Williams & Wllkins, 2005

de Vries EGE, van der Zee AG), Uges DRA et al. Excretion of platinum into breast milk. Lancet 1989; 1: 497-8,

Egan PC, Costanza MK. Dodion P et al. Doxorubicin and cisplatin excretion into human milk. Cancer Treat Rep 1985: 69: 1387-9.

French AE, Soldin SW. Soldin OP et al. Milk transfer and neonatal safety of tacrolimus. Ann Pharmacol Ii er 2003, 37: 815-18.

Gardiner S|, Begg E). Breastfeeding during tacrolimus therapy. Ohslct Gynecol 2006; 107:453-5.

Grekas DM, Vasiliou SS, Lazarides AN. Immunosuppressive Iherapy and breastfeeding after renal transplantation. Nephron 1984, 37: 68

Hale TW Jr. Medications and Mother's Milk, 12th edn. Amarillo, TX: Hale Publishing, 2006.

lain A, Venkatamaranan K, Fung JJ et al. Pregnancy after liver transplantation under tacrolimus, Transplantation 1997:64: 559-65,

Kharc MM. Lott [, Currie A et al. Is it safe to continue azathioprine in breast feeding mothers? J Obstet Gynaecol 2003: 23(Suppl 1): S48.

Kumar AR, HaleTW, Mock RE. Transfer of interferon alpha into human breast milk. I Hum Lactation 2000; 16(3): 226-8.

Mcrlob P. Ciclosporine during lactation. BELTIS-Newsletter, 2000; 67-73.

Moretti ME, Sgro M, Johnson DW et al. Cyclosporin excretion into breast milk. Transplantation 2003; 75(12): 2144-6.

Munoz-Flores-Thiagarajan KD, Easterling T, Davis C et al. Breast-feeding by a cyclosporine-treated mother. Obstet Gynecol 2001; 97: 816-18.

Nyberg G. Haljamäe U. Frisenette-Fich C et al. Breast-feeding during treatment with cyclosporine. Transplantation 1998; 65: 253-5.

Ostensen M, Eigenmann GO. Etanercept in breast milk. ) Rheumatol 2004; 31; 1017-18.

Swectman SC (ed.). Martindale. The Complete Drug Reference. 34th edn. London: Pharmaceutical Press. 2006.

Thiru Y. Bateman DN. Coulthard MG. Successful breastfeeding while mother was taking cyclosporine. Br Med J 1997; 315(7106): 463.

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