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Breast-feeding has important health and emotional benefits for both mother and infant, and should be encouraged. While there are some data to suggest migraine may improve during breast-feeding, more than half of women experience migraine recurrence with 1 month of delivery. Thus, a thorough knowledge base of the safety and recommended use of common acute and preventive migraine drugs during breast-feeding is vital to clinicians treating migraine sufferers. Choice of treatment should take into account the balance of benefit and risk of medication. For some of the medications commonly used during breast-feeding, there is not good evidence about benefits.
A list of commonly used migraine medications was agreed upon by the 6 authors, who treat migraine and other headaches on a regular basis and are members of the Women's Special Interest Section of the American Headache Society. Each medication was researched by the first author utilizing widely accepted data sources, such as the American Academy of Pediatrics publication “The Transfer of Drugs and Other Chemicals Into Human Milk; Thomas Hale's manual Medications and Mothers Milk; Briggs, Freeman, and Yaffe's reference book Drugs in Pregnancy and Lactation; and the National Library of Medicine's Drugs and Lactation Database (LactMed) – a peer-reviewed and fully referenced database available online.
Many commonly used migraine medications may be compatible with breast-feeding based on expert recommendations. Ibuprofen, diclofenac, and eletriptan are among acute medications with low levels in breast milk, but studies of triptans are limited. Toxicity is a concern with aspirin due to an association with Reye's syndrome; sedation or apnea is a concern with opioids. Finally, preventive medications not recommended include zonisamide, atenolol, and tizanidine.
Several excellent resources are available for clinicians making treatment decisions in breast-feeding women. Clinicians treating migraine should discuss both acute and preventive treatment options shortly before and within a few months after delivery, keeping in mind the clinical features of the individual patient, and in consultation with their obstetrician and pediatrician. An awareness of the pharmacological data that are currently available and how to access that data may be helpful in making treatment decisions in this population.
The majority of new mothers prefer to breast-feed their infants following delivery. Current standards suggest breast-feeding is the optimal form of infant nutrition, and is recommended by both the American College of Obstetrics and Gynecology and the American Academy of Pediatrics (AAP). Potential beneficial effects of breast-feeding for infants are numerous, and may include decreased risk of gastrointestinal illness,1 lower rates of atopic disease,2 and improved cognition.3 Breast-feeding may also benefit the mother by decreasing the risk of breast and ovarian cancer, and allowing a faster return to normal weight.4 Just over half of the women with migraine have recurrence of migraine in the first month after childbirth.5 Post-partum migraine occurrence may be delayed by breast-feeding, with most studies supporting breast-feeding as protective against migraine.5,6 However, some studies suggest that female migraineurs may not improve and continue to experience migraine attacks during lactation.7,8 A breast-feeding woman with migraine may forego treatment or even stop breast-feeding due to her fears of exposing her infant to medication. It is important to balance the risk of medication exposure with the benefit of migraine treatment. While many medications are considered to be compatible with breast-feeding, studies on breast-feeding women and their infants are rarely done due to obvious ethical concerns. However, cases of significant infant toxicity do exist, suggesting a careful, individualized risk assessment.
To some extent, most drugs transfer into breast milk. Exceptions include heparin and insulin as their size is too large to cross biological membranes. The transfer of drugs into breast milk is commonly described quantitatively using the milk to plasma (M/P) concentration ratio. The infant dose (mg/kg) can be expressed as a percentage of the maternal dose (mg/kg). A cut-off of 10% has been recommended as a guide for the safe use of most drugs during lactation, with a very low risk of infant effects.9,10 Multiple factors influence the transfer of drugs into human breast milk and infant exposure to those drugs. Those lipophilic drugs with small molecular size, low maternal plasma protein binding, and weakly basic pH compared with milk are likely to have greater concentrations in breast milk. However, drugs that are hydrophilic, inhaled or topical, or have a high maternal first-pass metabolism are less likely to be in breast milk. Additionally, the age of the infant should be considered: premature infants clear drugs poorly, while by 7 months of age infants clear drugs at a rate similar to adults.11
For drugs that appear in breast milk to any significant extent, it may be reasonable to reduce infant exposure by alternating breast and bottle-feeding, or by adjusting the timing of when the medication is taken relative to breast-feeding. This approach may be particularly useful for medications with a short half-life and acute migraine treatments.
While the potential effect of these medications on the nursing infant is the primary focus for the data collected, the primary objectives for this review article are as follows: (1) to summarize the current known data available for commonly used migraine medications used during lactation and (2) to provide a list of resources for clinicians to consult when making migraine treatment decisions in this population. It is hoped that this review article can be a valuable resource for headache clinicians treating lactating migraineurs.
A literature search was performed to determine the most highly regarded sources of information about the use of migraine medication during breast-feeding. Four sources of information were identified, and were agreed upon by all the authors of this article to be the most useful and most reliable source of information. The rationale for selecting these sources will be discussed in the following section.
The first author contacted the AAP to determine if clinical guidelines for migraine medication use during lactation have been established. The AAP does not have established evidence-based guidelines on treating migraine in lactation. However, they have a “retired” policy statement called “The Transfer of Drugs and Other Chemicals Into Human Milk.”12 This policy statement does not designate drugs as “safe” or “unsafe”; rather, it lists drugs and other agents into tables based on what is known or has been reported about the effect of the drug on the infant or on lactation, if known. The 7 tables are as follows:
A drawback of the AAP policy statement is that it was published in 2001 and has now been officially “retired” by the AAP. The designation of “retired” indicates that the 2001 publication no longer represents an official policy of the AAP. The AAP Committee on Drugs is preparing a new clinical report on selected therapeutics in lactation, with a projected completion in 2012. In the meantime, the AAP recommends the National Library of Medicine's Drugs and Lactation database (LactMed) as an excellent source of information concerning drugs to which breast-feeding mothers may be exposed. LactMed is a peer-reviewed and fully referenced database that is part of the National Library of Medicine's TOXNET system. It can be accessed at http://toxnet.nlm.nih.gov.13 The LactMed database includes information on drugs and lactation, including maternal levels of medications in breast milk, drug levels in infant blood, potential effects in breast-feeding infants, and effects on lactation. It is free and available for both providers and patients. A recent addition is a free downloadable application for handheld devices like iPhone. This database is updated every 1–2 months. LactMed does not assign any rating system to medication for lactation; it simply lists all that is known about a particular medication in regard to lactation.
A third resource is a comprehensive manual entitled Medications and Mothers Milk written by Thomas Hale, PhD.14 In this manual, the author reviews scientific literature and assigns a lactation risk category (LRC) to all listed medications. This manual is updated more frequently than theAAP policy statement. It was last published in 2010 as the 14th edition. It is available as a paperback book and can be ordered online at http://www.iBreastfeeding.com. This current edition is over 1000 pages. Medications are listed alphabetically using generic names. The index includes name brands to help locate the medication entry. Each drug monograph lists the pregnancy risk category as established by the Food and Drug Administration, Hale's LRC, and the AAP recommendations when available. Many medications have not been reviewed by the AAP committee. In this case, the monograph will state “not reviewed” for a particular drug. In addition, each listing shows the M/P ratio when it is known,potential drug interactions,and both adult and pediatric concerns. Hale's disclaimer in the manual's preface clarifies that he makes no recommendations as to the safety of these medications during lactation but only reviews what is currently published in the scientific literature. He emphasizes that individual use of medications must be left up to the judgment of the physician, the patient, and other health-care consultants. Hale's LRCs are listed in Table 1.
Another highly regarded and comprehensive reference examining the safety of medication in both pregnancy and lactation is Drugs in Pregnancy and Lactation by Briggs, Freeman, and Yaffe.15 The authors provide recommendations for breast-feeding based in large part on human data, such as milk and maternal plasma levels, infant drug levels after exposure, and reported adverse events. Their categories for breast-feeding recommendations are listed in Table 2.
For this paper, once the authors agreed upon the 4 reference sources, data for the use of migraine medication were collected and summarized. Commonly used migraine medications were divided into categories and listed by the generic names. The AAP rating given in the 2001 policy statement “Transfer of Drugs and Other Chemicals Into Human Milk,” as well as Hale's LRC, was listed for each medication. Hale's LRC was designated as L1, L2, L3, L4, or L5, with L1 being the safest and L5 contraindicated. The Briggs breast-feeding category is similarly listed.
In addition, the authors summarized the listings into tables for reference. Table 3 lists recommendations for commonly used acute migraine treatments, and Table 4 recommendations for commonly used migraine preventive drugs. In addition, each medication was researched by the first author of this review, utilizing LactMed for any additional up-to-date information. For details of the pharmacokinetics of each medication, including M/P ratio and maternal protein binding percentages, Hale's comprehensive manual and the Briggs/Freeman/Yaffe reference were used.
The AAP policy statement and the LRC as assigned by the Hale or the Briggs manual of a drug will often be different than what is found in the Physicians Desk Reference (PDR). This is because the PDR is a compendium of pharmaceutical manufacturers' package inserts. Most package inserts will designate drugs not to be used during breast-feeding due to lack of clinical studies done in breast-feeding mothers.
In this section, commonly used migraine preventive medications will be divided into categories and listed alphabetically. Hale's LRC, Briggs category, and the AAP rating will be listed. For medications not listed, clinicians are encouraged to use the resources listed in this article to get information about use during lactation.
There is little known information about the safety of many nutraceutical products in breast-feeding.This includes preventive treatments for migraine, such as coenzyme Q10 and petasites (butterbur), although coenzyme Q10 is present in breast milk normally.53
There are no evidence-based guidelines for the treatment of migraine during breast-feeding. Current data and recommendations are limited by the lack of clinical studies done in breast-feeding women and the very small numbers reported in case reports or small published studies. However, despite these limitations, there are many treatment options for migraine that are compatible with breast-feeding. Excellent resources are available to help clinicians in making treatment decisions in the breast-feeding female migraine patient. Suggested resources include the following:
An open discussion with our patients about available resources, and the risks and benefits of various medications while nursing, can foster a collaborative approach to migraine treatment during breast-feeding. Consideration of potential efficacy should be taken into account when making treatment decisions. Updated guidelines for the prevention of episodic migraine were completed in 2012 by the American Headache Society and the American Academy of Neurology.54 Awareness of these guidelines, including the level of evidence for a particular medication being considered, should be considered when making treatment decisions in breast-feeding women. For acute migraine treatment, the United States Headache Consortium Guidelines can be helpful in balancing safety with efficacy of a particular treatment.55 The best approach is often to see the patient in the third trimester before giving birth to discuss if the mother will breast-feed after giving birth, and the potential risks of acute and preventive migraine medication. For acute migraine, medications with very low absorption into breast milk may be appropriate, with no need to discontinue breast-feeding. As examples, ibuprofen and eletriptan have very low levels in breast milk, and many acute medications have short half-lives, making it fairly easy to briefly discontinue breast-feeding. The decision to use preventive medication while breast-feeding is more complicated. For women with a history of refractory migraine, long-lasting or especially disabling migraine, or history of migraine worsening soon after a previous pregnancy, it may be reasonable to start preventive medication immediately after giving birth and bottle feeding, or to only use preventive medication with very low concentrations in breast milk. For women previously treated successfully with a particular preventive, it may be worth restarting that same medication soon after delivery. For women with episodic migraine for whom acute medications are effective and in those doing well during pregnancy, it may be reasonable to delay preventive medication to allow women to breast-feed. Breast-feeding while taking medications may be higher risk to preterm infants in their first month or two as their ability to metabolize drugs is lower.
A follow-up visit after giving birth should address migraine frequency and severity if the mother is breast-feeding, and if so how long she plans to do so. The majority of women breast-feed in the early post-partum period, but less than half of women continue to breast-feed at 6 months and only about 30% of women exclusively breast-feed at 3 months.56 A few medications that are considered high risk in pregnancy may be relatively safer for breast-feeding due to low concentrations in breast milk, such as valproate. Starting at lower doses and titrating up more slowly than usual is 1 strategy. For example, when starting topiramate, this might mean starting at 15 mg instead of 25 mg, or increasing the dose every 2–3 weeks instead of weekly. For tricyclic antidepressants, such as amitriptyline or nortriptyline, this may mean starting at 10 mg rather than 25 mg. Starting at low doses allows the ability to assess for any adverse effects on the infant, such as sedation, and within the first months of life infant metabolism rapidly increases.
In the absence of controlled clinical trials and evidence-based guidelines, health care providers can strive to make good treatment decisions based on the pharmacological data that are currently available. Our migraine patients desirous of breast-feeding will benefit from our awareness of what is known about medication use during breast-feeding.
Source of Funding: None.
Conflict of Interest: S.H., M.M., A.C., S.L., and S.S. have no conflicts of interest relevant to this paper. B.L.P. receives salary support through the National Institute of Neurological Disorders and Stroke (K2310896737).