PL Detail-Document #280211

This PL Detail-Document gives subscribers additional insight related to the Recommendations published in

PHARMACISTS LETTER / PRESCRIBERS LETTER

February 2012

Analgesics in Pregnancy and Lactation

Acetaminophen is the drug of choice for pain in pregnancy and lactation.1-3 NSAIDs should generally be avoided during pregnancy, but ibuprofen is an option for nursing moms.3 Avoid aspirin in analgesic doses.5,12 In some cases, an opioid may be the only option. Our PL Detail-Document, New Pregnancy Warnings: Opioids, Topiramate, and Antipsychotics, describes a case-control study of opioids (mostly codeine, oxycodone, hydrocodone, and meperidine) and birth defects.11 The study authors concluded that opioid use between one and three months after conception is associated with a number of birth defects.11 However, the risk, if it exists, is likely small, and the benefits of pain management with opioids may outweigh the risks.11 Newborns are sensitive to even small doses of opioids, especially in the first week of life. But newborn exposure is limited during the first two to three postpartum days because of the small volume of colostrum.3 So try to get the patient switched to a nonopioid within four days of delivery. If an opioid is used during lactation, monitor for signs of opioid exposure in the breastfed infant (e.g., limpness, difficulty feeding or breathing, or sleeping more than usual).3 Use the smallest dose necessary of a low-potency, short-acting agent (e.g., codeine), taken after feeding, for the shortest duration necessary.2,13,15,17 Moms feeling sleepy or groggy should try taking less opioid to reduce infant exposure.9 The following chart includes information to help guide decisions regarding analgesic use in pregnancy and lactation. FDA pregnancy categories have several limitations and are not included. Drug or Drug Class Acetaminophen Use in Pregnancy Generally considered the analgesic/antipyretic of choice in pregnant women.1 Not linked to birth defects.1 Avoid as an analgesic. Use acetaminophen instead.5 Low doses may have favorable risk/benefit for certain complicated pregnancies.5 Small to moderate association between first trimester use and small or absent eyes, neural tube defects, oral clefts, amniotic band syndrome causing limb or body wall defects, and pulmonary valve stenosis.16 May cause maternal or fetal bleeding.4 High doses may cause perinatal mortality, intrauterine growth restriction, and premature Use in Lactation Good analgesic/antipyretic choice for nursing moms;2,3 amount in milk less than therapeutic doses given to infants.3 Adverse effects in breastfed infants are rare. Case report of rash.3 Avoid analgesic doses;12 metabolic acidosis reported.3 Acetaminophen is a safer analgesic choice.2

Aspirin

Continued

More. . .
Copyright 2012 by Therapeutic Research Center P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com

(PL Detail-Document #280211: Page 2 of 5)

Drug or Drug Class Aspirin, continued

Use in Pregnancy closure of ductus arteriosus (third trimester).5 Avoid during last four to eight weeks of pregnancy.12 Unproven link to gastroschisis. Otherwise, not linked to birth defects.4 Generally avoid; acetaminophen preferred. If needed, use lowest effective dose, intermittently if possible, especially in late pregnancy.4,12 First trimester use linked to miscarriage.6 Small to moderate association with small or absent eyes, neural tube defects, oral clefts, amniotic band syndrome causing limb or body wall defects, and pulmonary valve stenosis.6,16 Not a proven teratogen.4 Third trimester use poses risk of premature closure of ductus arteriosus, fetal renal toxicity, and inhibition of labor.5 Avoid during last eight weeks of pregnancy.4 Most info based on use for opioid dependence, not analgesia. Not a preferred opioid due to lack of human data.5 No first trimester data. No reports of congenital malformations.5 Use during labor associated with sinusoidal fetal heart rate and neonatal depression.5 Use in first and second trimester associated with a variety of malformations (e.g., heart defects, cleft lip and palate, musculoskeletal defects, hernia).5

Use in Lactation

NSAIDs (e.g., ibuprofen, etc.)

Ibuprofen is the NSAID of choice for nursing moms; half-life short, amount in milk less than therapeutic doses given to infants.3

Opioidsa,b Buprenorphine

Use considered acceptable based on oral use for opioid dependence, not analgesia.3 Consider alternative due to lack of information when used as an analgesic. Considered compatible with breastfeeding,2 but no info with repeated, high, intravenous, or intranasal doses.3 Amount in breast milk is small, and is poorly absorbed.3 Consider alternatives due to paucity of information.3 Risk of morphine (codeine metabolite) toxicity if mom is an ultrarapid CYP2D6 metabolizer.c Monitor, and use lowest effective dose for shortest time possible.7,8 Use smallest dose necessary, and limit duration to four days.3
More. . .

Butorphanol

Codeine

Copyright 2012 by Therapeutic Research Center P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com

(PL Detail-Document #280211: Page 3 of 5)

Drug or Drug Class Fentanyl Hydrocodone (e.g., Vicodin, Lortab [U.S.])

Use in Pregnancy No reports of congenital malformations.5 First trimester use associated with cardiovascular and other defects.5

Use in Lactation Considered compatible with breastfeeding,2 but use smallest dose necessary for shortest duration necessary.3 Excessive sleepiness and cyanosis reported in two case reports.10 Active metabolite (hydromorphone) formed through CYP2D6 is more potent than oxycodone.10 Theoretical risk of hydromorphone (hydrocodone metabolite) toxicity if mom is an ultrarapid metabolizer.10,c Use smallest dose necessary for shortest duration necessary.3 Maximum daily dose of 30 mg suggested for nursing moms.3 Excreted in breast milk. Use smallest dose necessary for shortest duration necessary.3 Newborns have trouble clearing meperidine.3 Not a preferred agent for oral, intravenous, or intramuscular use for breastfeeding mom, especially if nursing a newborn or preterm infant.3 Higher risk vs morphine.14 Postpartum epidural PCA usually not sedating to breastfed infants.3 Single dose for anesthesia usually not problematic in older infants.3 Considered compatible with breastfeeding.2 Infant can have detectable morphine levels.2 Epidural administration leads to lower levels in milk than oral or intravenous administration.3 Use smallest parenteral dose necessary for shortest duration necessary.3 Small amount in breast milk. Poor oral absorption. Unlikely to affect infant.3
More. . .

Hydromorphone (Dilaudid)

Meperidine

No reports of congenital malformations.5 Use during labor expected to produce neonatal respiratory depression risk similar to morphine or meperidine.5 No clear association with congenital malformations.5 Newborn clears meperidine slowly. Concerns about neurologic effects on newborn if used during labor. Use during labor expected to produce neonatal respiratory depression risk similar to hydromorphone or morphine.5 No clear association with congenital malformations.5 Use during labor expected to produce neonatal respiratory depression risk similar to hydromorphone or meperidine.5 No reports of congenital malformations.5

Morphine

Nalbuphine (Nubain)

Copyright 2012 by Therapeutic Research Center P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com

(PL Detail-Document #280211: Page 4 of 5)

Drug or Drug Class Oxycodone (e.g., Percocet, etc.)

Use in Pregnancy No clear association with congenital malformations.5

Use in Lactation Physicochemical properties suggest it may accumulate in breast milk.10 Oxycodone elimination is impaired in young infants and varies interindividually.3 Active metabolite (oxymorphone) formed through CYP2D6 is 14 times more potent than oxycodone.10 Theoretical risk of oxymorphone (oxycodone metabolite) toxicity if mom is an ultrarapid metabolizer (see codeine).c One in five infants of moms taking oxycodone experience CNS depression, similar to codeine.10 Use smallest dose necessary for shortest duration necessary.3 Maximum daily dose of 30 mg suggested for nursing moms.3 No data in humans.5 Potential to accumulate in breast milk based on physicochemical properties.5 Small amount in breast milk. Appears well-tolerated in breastfed infants. Use acceptable.3

Oxymorphone

No human data, other than neonatal respiratory depression, as expected, if used during labor.5 No human data.5 Probably crosses placenta.5 Animal data suggest no congenital malformations at exposures not causing maternal toxicity.5 Animal data suggest embryo/fetotoxicity; avoid in first trimester.5 Not clearly safer than traditional opioids.5,b

Tapentadol (Nucynta (U.S.), Nucynta CR [Canada]) Tramadol (Ultram, etc.)

a. Reserve opioids for pain that cant be managed with acetaminophen. Use lowest effective dose for shortest time possible. Watch baby for limpness, difficulty feeding or breathing, or sleeping more than usual.3 b. Opioid use during labor can cause neonatal respiratory depression, and long-term use during pregnancy may result in neonatal withdrawal. c. Ultrarapid CYP2D6 metabolism occurs in up to 10% of Caucasians; 3% of African-Americans; 1% of Chinese, Japanese, and Hispanics; and up to 28% of North Africans, Saudis, and Ethiopians.8
Users of this PL Detail-Document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and internet links in this article were current as of the date of publication. More. . .
Copyright 2012 by Therapeutic Research Center P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com

(PL Detail-Document #280211: Page 5 of 5)

Project Leader in preparation of this PL DetailDocument: Melanie Cupp, Pharm.D., BCPS

9.

References
1. Rebordosa C, Kogevinas M, Bech BH, et al. Use of acetaminophen during pregnancy and risk of adverse pregnancy outcomes. Int J Epidemiol 2009;38:70614. American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89. National Institutes of Health. United States National Library of Medicine. TOXNET Toxicology Data Network. Drugs and Lactation Database (LactMed). http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT. (Accessed December 5, 2011). Babb M, Koren G, Einarson A. Treating pain during pregnancy. January 2010. http://www.motherisk.org/prof/updatesDetail.jsp?cont ent_id=922. (Accessed December 5, 2011). Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2011. Nakhai-Pour HR, Broy P, Sheehy O, Berard A. Use of nonaspirin nonsteroidal anti-inflammatory drugs during pregnancy and the risk of spontaneous abortion. CMAJ 2011;183:1713-20. Health Canada. Information for healthcare professionals: use of codeine products in nursing mothers. October 8, 2008. http://www.hcsc.gc.ca/dhp-mps/medeff/advisoriesavis/prof/_2008/tylenol_codeine_hpc-cps-eng.php. (Accessed December 5, 2011). FDA. Information for healthcare professionals: use of codeine products in nursing mothers. August 17, 2008. http://www.fda.gov/drugs/drugsafety/postmarketdrug safetyinformationforpatientsandproviders/ucm124889 .htm. (Accessed January 17, 2012).

10.

11.

2.

12.

3.

13.

4.

14. 15.

5.

6.

16.

7.

17.

Lam J, Kelly L, Ciszkowski C, et al. Central nervous system depression of neonates breastfed by mothers receiving oxycodone for postpartum analgesia. J Pediatr 2012;160:33-7. Anderson PO, Sauberan JB, Lane JR, Rossi SS. Hydrocodone excretion into breast milk: the first two reported cases. Breastfeed Med 2007;2:10-4. Broussard CS, Rasmussen SA, Reefhuis J, et al. Maternal treatment with opioid analgesics and risk for birth defects. Am J Obstet Gynecol 2011;204:314.e1-11. Janssen NM, Genta MS. The effects of immunosuppressive and anti-inflammatory medications on fertility, pregnancy, and lactation. Arch Intern Med 2000;160:610-9. Organization of Teratology Information Specialists (OTIS). March 2011. Prescription opioids and pregnancy. http://www.otispregnancy.org/files/rxopioids.pdf. (Accessed December 6, 2011). Ito S. Drug therapy for breast-feeding women. N Engl J Med 2000;343:118-26. Van den Anker JN. Is it safe to use opioids for obstetric pain while breastfeeding? J Pediatr 2012;160:4-6. Hernandez RK, Werler MM, Romitti P, et al. Nonsteroidal antiinflammatory drug use among women and the risk of birth defects. Am J Obstet Gynecol 2011 Dec 1 [Epub ahead of print]. Matthews JK. Questions breastfeeding moms ask about OTC medications. http://otcsafety.org/en/experts/questionsbreastfeeding-moms-ask-about-otc-medicines/. (Accessed January 17, 2012).

8.

Cite this document as follows: PL Detail-Document, Analgesics in Pregnancy and Lactation. Letter/Prescribers Letter. February 2012.

Pharmacists

Evidence and Recommendations You Can Trust

3120 West March Lane, P.O. Box 8190, Stockton, CA 95208 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249
Copyright 2012 by Therapeutic Research Center

Subscribers to the Letter can get PL Detail-Documents, like this one, on any topic covered in any issue by going to www.pharmacistsletter.com, www.prescribersletter.com, or www.pharmacytechniciansletter.com