What - GoMidwife



BreastfeedingAssignment #9 – MedicationsDue Sunday, March 28, 2021Part 1A. Read the following:– Breastfeeding and Medications by Dr. Jack Newman: Over the years, far too many mothers?have been?wrongly?told they had to stop breastfeeding because they must take a particular drug. The decision about continuing breastfeeding when the breastfeeding parent?takes a drug, for example, is far more involved than whether the baby will get any in the milk. It also involves taking into consideration the risks of not breastfeeding, for the breastfeeding parent, the baby and the family, as well as society. And there are plenty of risks in not breastfeeding, so the question essentially boils down to:?Does the addition of a very small amount of medication to the breastfeeding parent’s milk make breastfeeding more hazardous than formula feeding??The answer is?almost?never. Breastfeeding with a little drug in the milk is almost always safer. In other words, being careful means continuing breastfeeding, not stopping.Most drugs appear in the milk, but usually only in tiny, even minuscule amounts. Although a very few drugs may still cause problems for infants even in minuscule?doses, this is not true?for the vast majority. Breastfeeding parents who are told they must stop breastfeeding because of a certain drug should ask the physician to make sure of this by checking with reliable sources.? Note that the CPS (in Canada) and the PDR (in the USA) are not reliable sources of information about drugs and breastfeeding.? These “resources” are merely a compilation of the information provided by the drug manufacturers who are more interested in their medical legal liability than the interests of the mother and baby.? Their policy is essentially “We can’t be held responsible if we advise the breastfeeding parent to interrupt breastfeeding”.? But if there is a real concern in the rare case,?the breastfeeding parent should ask the physician to prescribe an alternate medication that is acceptable during breastfeeding.One of the rare cases [to not take while breastfeeding] is the use of letrozole?(Femara) to induce ovulation. Although not contraindicated during breastfeeding and like all drugs appearing only in tiny amounts in the milk, it is better not to use in the breastfeeding mother. ?However, there are alternatives to induce ovulation that are safe.Most Drugs Are Safe If:The amount the baby would get through the milk is much less than he would get if given directly.?They are considered safe in pregnancy. This is not always true, since during the pregnancy, the pregnant parent’s body is helping the baby get rid of drug. Thus it is theoretically possible that worrisome accumulation of the drug might occur during breastfeeding when it wouldn’t during pregnancy (though this is rare). ?However, if the concern is for the baby’s being?exposed to a drug, say an antidepressant, then the baby is getting exposed to much more drug at a much more sensitive time during pregnancy than during breastfeeding.? They are not absorbed from the stomach or intestines. These include many, but not all, drugs given by injection. Examples are gentamicin (and other drugs in this family of antibiotics such as tobramycin), heparin, interferon, local anaesthetics, omeprazole.? Omeprazole (Losec, Prilosec) and other drugs of this family of proton pump inhibitors such as lansoprazole (Prevacid), pantoprazole (Tecta) and others are interesting because they are destroyed very quickly by stomach acid. During the manufacture of the drug, a protective layer is added to these drugs to prevent their destruction by stomach acid and such drugs are absorbed into the breastfeeding parent’s body. However, when the baby gets the drug (in minuscule?amounts incidentally) there is no protective layer on the drug, so it is immediately destroyed in the baby’s stomach.They are not excreted into the milk. Some drugs are just too big to get into the milk. Examples are heparin, interferon, insulin, infliximab (Remicade), etanercept (Enbrel) and a host of new monoclonal antibodies (or biologicals). Indeed, even if any of the previously mentioned drugs did get into the milk (they don’t) they would be destroyed in the baby’s stomach.The Following Are A Few Commonly Used Drugs Considered Safe During Breastfeeding:Acetaminophen (Tylenol, Tempra), alcohol (in reasonable amounts), aspirin (in usual doses, for short periods). Most antiepileptic medications, most antihypertensive medications, tetracycline, doxycycline?codeine, nonsteroidal antiinflammatory medications (such as ibuprofen), prednisone, thyroxin, propylthiouracil (PTU), methimazole, warfarin, tricyclic antidepressants, sertraline (Zoloft), paroxetine (Paxil), other antidepressants, metronidazole (Flagyl), omeprazole (Losec), Nix, Kwellada.Note: Though generally safe, fluoxetine (Prozac) has a very long half-life (stays in the body for a long time).? Thus, a baby born to a parent?on this drug during the pregnancy, will have large amounts in his body, and even the small amount added during breastfeeding may result in significant accumulation and side effects. These are rare, but have happened. There are two options that you might consider:?Stop the fluoxetine (Prozac) for the last 4 to 8 weeks of your pregnancy. In this way, you will eliminate the drug from your body and so will the baby. Once the baby is born, he will be free of drug and the small amounts in the milk will not usually cause problems and you can restart the fluoxetine (Prozac).If it is not possible to stop fluoxetine (Prozac) during your pregnancy, consider changing to another drug that does not get into the milk in significant amounts once the baby is born. Two good choices are sertraline (Zoloft) and paroxetine (Paxil).Medications applied to the skin or inhaled (for example, drugs for asthma) or applied to the eyes or nose, are almost always safe for breastfeeding.Drugs for local or regional anaesthesia are not absorbed from the baby’s stomach and are safe. Drugs for general anaesthesia will get into the milk in only tiny amounts (like all drugs) and are extremely unlikely to cause any effects on your baby. They usually have very short half-lives and are eliminated extremely rapidly from your body. You can breastfeed as soon as you are awake and up to it.Immunizations given to the breastfeeding parent do not require breastfeeding to be stopped. On the contrary, the immunization will help the baby develop immunity to that immunization, if anything gets into the milk. In fact, most of the time nothing does get into the milk, except, possibly some of the live virus immunizations, such as German Measles. And that’s good, not bad.X-rays and scans. Ordinary X-rays do not require a breastfeeding parent to interrupt breastfeeding even when used with contrast material (example, intravenous pyelogram). The reason is that the material does not get into the milk, and even if it did it would not be absorbed by the baby. The same is true for CT scans and MRI scans. You do not have to stop for even a second.?What About Radioactive Scans??We do not want babies to get radioactivity, but we rarely hesitate to do radioactive scans on them. When a breastfeeding parent?gets a lung scan, or lymphangiogram with radioactive material, or a bone scan, it is usually done with technetium (though other materials are possible).? Technetium has a half-life (the length of time it takes for ? of all the drug to leave the body) of 6 hours, which means that after 5 half-lives it will be gone from the breastfeeding parent’s body (do the math). Thus, 30 hours after injection, all of it will be gone (well 98% will be gone) and the breastfeeding parent?can breastfeed the baby without concern about the baby?getting radiation. But does all the radioactivity need be gone? After 12 hours, 75% of the technetium is gone, and the concentration in the milk very low. I think that waiting 2 half-lives is enough, for a material such as technetium. But: Not all technetium scans require stopping breastfeeding at all (HIDA scan, for example).? It depends on which molecule the technetium is attached to.? In the first few days, there is very little milk (though there is enough).? In this situation it would be unnecessary for the mother to stop breastfeeding after a lung scan, for example.? However, one of the most common reasons to do a lung scan is to diagnose a blood clot in the lung.? This can now be done better and faster with CT scan, which does not require interrupting breastfeeding for even 1 second.If you decide that interruption of breastfeeding is the best course to follow, (though we emphasize again that it is almost never necessary), then express milk for several days in advance (if you have advance warning about the test) and this can be fed via cup for a few days. Then while not breastfeeding, express your milk but don’t throw away the milk.? The radioactive tracer that is present in the milk decays and the radiation is gone in 5 half-lives.? So, even for I??? used in thyroid scans (see below), the radioactivity of the iodine will be gone in 5 half-lives, so the milk can be used in 6 to 8 weeks (the half-life of I??? is about 8 days). Only occasionally is a radioactive scan so urgent that it cannot be delayed for a few days. ?In fact, there are other ways of diagnosing thyroid problems than with radioactive iodine. ?And better ways of treating hyperthyroidism than radioactive iodine.Thyroid scans are different. Radioactive iodine (I???) is concentrated in milk and will be ingested by the baby and it will go to his thyroid where it will stay for a long time. This is definitely of concern. So, the breastfeeding parent will have to stop breastfeeding? No, because often the test does not need to be done at all. Differentiating postpartum thyroiditis from Graves’ Disease (the most common reason for doing the scan in breastfeeding parents) does not require a thyroid scan. Get more information from the clinic.? If a scan needs to be done, it is possible to do a thyroid scan I??? which requires stopping for only 12 to 24 hours, depending on the dose given or technetium (see above).? Don’t forget to express milk in advance so the baby can get it instead of formula.?– references are NOT good sources for information on medications and breastfeeding:It is not appropriate to use pregnancy risk categories (A,B,C,D,X…) to determine the risk of a drug to a breastfeeding mother and her baby, since the entry of drugs into human milk is quite different than the entry of drugs across the placenta during pregnancy.It is not uncommon to see doctors using the Physicians Desk Reference for information on medications and nursing. This reference contains the package inserts from the pharmaceutical manufacturers. Almost across the board, they indicate that each medication should not be taken while pregnant or breastfeeding. The warning statements they use are designed to protect themselves from lawsuits. When considering a medication (including herbal and other “natural” preparations) here are several factors to take into account:Does the mother need this medication/treatment right now, or is it something that she does not need or can easily postpone until her child is older?How old is the breastfeeding child? Is s/he healthy? Premature babies, newborns, and babies with health problems require somewhat more caution when it comes to the medications that the mother is taking; healthy older babies and toddlers are generally at a lesser risk since their bodies can metabolize medications more easily.How much breastmilk does the child get? A child who is getting smaller amounts of breastmilk (a newborn in the early days before mother’s milk volume naturally increases, a baby or child who is eating other foods in addition to breastmilk and breastfeeds less often, etc.) will also be getting less of any medication that passes into breastmilk.Is the medication in question one with a record of safely being given directly to babies and young children? The amount of the medication that passes into breastmilk will normally be significantly lower than that given directly to young children.Avoid medications known to affect milk production.Temporary weaning is a risk to the mother’s?milk supply. Milk supply may be compromised since pumps do not provide the same stimulation to supply as does a nursing baby. For the rare times when temporary weaning is needed, see this information on?maintaining milk supply when baby is not nursing.Temporary weaning comes with a risk that baby will not go?back to the breast. Some babies have a hard time returning to breastfeeding after temporary weaning, and unfortunately we do not know ahead of time which babies will have problems.There are?known risks of formula feeding, including allergy, increased illness, etc. Many of the risks of formula feeding are not apparent for many years.– link had an error on the site and does not load.– Potential Risk to Nursing Infants from Maternal MedicationsGeneral considerationsAvoid drug therapy when possible.Use topical therapy when possible.Medications that are safe for use directly in an infant of the nursing infant's age are generally safe for the breast-feeding mother.Medications that are safe in pregnancy are not always safe in breast-feeding mothers.Use reliable references for obtaining information on medications in breast milk.Medication selectionChoose medications with the shortest half-life and highest protein-binding ability.Choose medications that are well-studied in infants.Choose medications with the poorest oral absorption.Choose medications with the lowest lipid solubility.Medication dosingAdminister single daily-dose medications just before the longest sleep interval for the infant, usually after the bed-time feeding.Breast-feed infant immediately before medication dose when multiple daily doses are needed.Fortunately, for certain common conditions, general recommendations can be made regarding the use of medications in the treatment of nursing mothers. Greater precaution is advised when prescribing medications for mothers of premature or otherwise compromised infants or newborns in the first week of life than for older, healthy infants.Specific ConditionsALLERGIC RHINITISPseudoephedrine (Sudafed) is excreted in breast milk in small amounts. According to the AAP, its use is compatible with breastfeeding although it may cause decreased milk production.6, HYPERLINK "" \l "afp20010701p119-b7" 7 Diphenhydramine (Benadryl), which is frequently prescribed for children, is also excreted in breast milk in small quantities. Either of these medications can cause lethargy or irritability in infants. To reduce the risk to the infant, the mother can take these medications immediately after breastfeeding. The new, nonsedating antihistamines are not well-studied in breast-feeding and are not rated by the AAP. Because they have fewer effects on the central nervous system and are safe for use in children, these antihistamines are preferred for short-term use in breastfeeding women.7 For long-term treatment, nasal steroids or cromolyn (Intal) are safer alternatives.7, HYPERLINK "" \l "afp20010701p119-b8" 8ASTHMAInhaled steroids for the treatment of asthma achieve very low levels in maternal plasma and are of no concern for the breastfeeding mother. Fluticasone (Flovent) has the lowest serum levels of the inhaled steroids. Oral steroids such as prednisone (Deltasone) and prednisolone (Delta-Cortef) penetrate into the breast milk poorly and are safe for short-term use. When daily dosages exceed 20 mg, prednisolone may be preferred over prednisone because it has only one peak in activity while prednisone has two peaks in activity—one for the pro-drug (prednisone) and the other for the drug (prednisolone).8 Infant exposure can be minimized by with holding nursing for four hours after taking the medication.3, HYPERLINK "" \l "afp20010701p119-b7" 7CARDIOVASCULARDiuretics and beta blockers, commonly preferred antihypertensives, are safe for use in lactating women, with some precautions. In general, it is preferable to avoid high dosages of any one medication by either changing medications or adding an additional agent.9Low dosages of thiazide diuretics (e.g., 25 mg per day or less of hydrochlorothiazide [Esidrix]) are excreted in small amounts into the breast milk but do not suppress lactation and, consequently, are compatible with nursing.6, HYPERLINK "" \l "afp20010701p119-b9" 9 Beta blockers vary widely in the amount excreted into breast milk. Propranolol (Inderal), metoprolol (Lopressor) and labetalol (Normodyne) are excreted in small quantities and are compatible with breastfeeding even in compromised infants. Atenolol (Tenormin), nadolol (Corgard) and sotalol (Betapace) are excreted in higher amounts, which can lead to hypotension, bradycardia and tachypnea in the infant.9Maternal depression is known to have an adverse effect on parenting and infant development.14 Tricyclic antidepressants have been shown to have little to no effect on the breastfeeding infant, although the AAP finds most tricyclic agents to be of possible concern.3, HYPERLINK "" \l "afp20010701p119-b7" 7 Taking a single daily dose at bedtime will limit the infant's exposure to the medication. The selective serotonin reuptake inhibitors (SSRIs) are generally the first choice of treatment for depression. Sertraline (Zoloft) is likely to be the safest choice among them because it has been studied extensively and because drug levels found in nursing infants are usually minimal.7, HYPERLINK "" \l "afp20010701p119-b12" 12Fluoxetine (Prozac) use during pregnancy has been well-studied, and many new mothers are already taking it at delivery. Its use during breast-feeding is controversial, however. Fluoxetine's long half-life and potential for accumulation in breast milk has prompted some recommendations to avoid its use in women who are breast-feeding young infants.3 Colic and fussiness have been attributed to elevated serum concentrations of fluoxetine and its metabolite in nursing infants.4 Results from a recent study showed a decrease in the level of fluoxetine and its metabolite in the early weeks of life in nursing infants whose mothers were maintained on fluoxetine throughout pregnancy and breast-feeding. This decrease implies an absence of accumulation of fluoxetine during exposure from breast milk.15 No long-term studies of neurologic outcomes of children with breast milk exposure to SSRIs are available. These children should be observed closely.At this time, it seems prudent to choose an SSRI with the lowest plasma levels in infants, such as sertraline (Zoloft) or paroxetine (Paxil).7, HYPERLINK "" \l "afp20010701p119-b14" 14 Another option is to measure serum concentrations of the SSRI and major metabolites in the infant at two to six weeks postpartum to verify that the medication is not accumulating. If the mother has taken fluoxetine during pregnancy, an infant serum level of fluoxetine and norfluoxetine at about six weeks should reflect drug accumulation from the breast milk instead of continued presence of the prenatal medication.15Of the nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen (Motrin) is the preferred choice because it has poor transfer into milk and has been well-studied in children. Long half-life NSAIDs such as naproxen (Naprosyn), sulindac (Clinoril) and piroxicam (Feldene) can accumulate in the infant with prolonged use.7Medications Not to Be Used in Breast-Feeding MothersAntineoplastic agentsErgotamine tartrate (Ergomar)Bromocriptine (Parlodel)LithiumCyclophosphamide (Cytoxan)Methotrexate (Rheumatrex)Cyclosporine (Sandimmune)Radiopharmaceuticals*– B. Take notes as you will use them in the second partPart 2The societies we work in often have traditions, customs, and realities that are different than what we may be used to. Even in our own communities we can often find that things are done differently between one family and another. This is true in many areas, but one of those that you might be questioned about from time to time is the effect of medication in particular and drugs more broadly when it comes to breastfeeding. If a woman is taking medications or using drugs there are times when this will affect breast milk, and potentially her child, and times when it may not. In this part of the assignment you will examine some of the more common drugs and medications you may run across.Each drug and interaction in breast milk should be 3 paragraphs in length.Using the readings above as well as other outside information you may have access to, research and write about the effects of the following drugs in breast milk:MarijuanaDrug Levels and EffectsSummary of Use during LactationThe main psychoactive component of cannabis, tetrahydrocannabinol (THC), is excreted into breastmilk in small quantities. The duration of detection of THC in milk has ranged from 6 days to greater than 6 weeks in various studies. Concern has been expressed regarding the possible effects of cannabis on neurotransmitters, nervous system development and endocannabinoid-related functions.[1,2] A 1-year study found that daily or near daily use might retard the breastfed infant's motor development, but not growth or intellectual development.[3] This and another study[4] found that occasional maternal cannabis use during breastfeeding did not have any discernable effects on breastfed infants, but the studies were inadequate to rule out all long-term harm. Although cannabis can affect serum prolactin variably, it appears not to adversely affect the duration of lactation. However, maternal perception that their use of cannabis is harmful to their infants are likely to discontinue breastfeeding earlier than mothers who do not believe it is harmful.[5] Other factors to consider are the possibility of positive urine tests in breastfed infants, which might have legal implications, and the possibility of other harmful contaminants in street drugs.Because of insufficient long-term data on the outcome of infants exposed to cannabis via breastmilk, health professionals' opinions on the acceptability of breastfeeding by cannabis-using mothers varies. In general, professional guidelines recommend that cannabis use should be avoided by nursing mothers, and nursing mothers should be informed of possible adverse effects on infant development from exposure to cannabis compounds in breastmilk. In addition to possible adverse effects from cannabinoids in breastmilk, paternal cannabis use may also increase the risk of sudden infant death syndrome in breastfed infants. Cannabis should not be smoked by anyone in the vicinity of infants because the infants may be exposed by inhaling the smoke.[ HYPERLINK "" 6-9]Drug LevelsThe main active psychoactive component of cannabis is delta-9-tetrahydrocannabinol (THC), although it also contains other active compounds. THC is very fat soluble and persistent in the body fat of users and slowly released over days to weeks, depending on the extent of use.Maternal Levels. Two women who smoked marijuana daily while nursing had their randomly collected milk analyzed. One mother who reported smoking marijuana once daily had a milk tetrahydrocannabinol concentration of 105 mcg/L; other metabolites were absent. The second mother who reported smoking marijuana 7 to 8 times daily had a milk concentration of 340 mcg/L; the metabolite 11-hydroxy-THC was found in a concentration of 4 mcg/L and 9-carboxy-THC was absent. A milk sample that was collected 1 hour after smoking marijuana contained 60.3 mcg/L of THC, 1.1 mcg/L of 11-hydroxy-THC and 1.6 mcg/L of 9-carboxy-THC.[10] One source used data in this case to estimate that the infant receives about 0.8% of the maternal weight-adjusted dosage.[11] However, a poorly characterized assay was used that might not be accurate and the portion of milk (i.e., foremilk versus hindmilk) that was collected by the mothers was not stated. This is important because of the high fat solubility of THC.A woman who admitted to smoking cannabis (amount not stated) donated milk for analysis at an unknown time after the previous use. THC was present in a concentration of 86 mcg/L and 11-hydroxy-THC was present in a concentration of 5 mcg/L; 11-nor-carboxy-9-tetrahydrocannabinol was not detected.[ HYPERLINK "" 12]Eight exclusively nursing women who were 3 to 5 months postpartum and reported previous or current cannabis smoking were studied. After 24 hours of abstinence, each smoked a 100 mg of a standardized cannabis containing 23.18% THC. The product was smoked over 10 to 20 minutes from a glass pipe until it was fully consumed. Milk was pumped before smoking and at 20 minutes, 1, 2 and 4 hours after inhalation. THC and its metabolites, 11-OH-delta-9-tetrahydrocannabinol and 11-nor-9-carboxy-delta-9-tetrahydrocannabinol were measured in the milk samples. Six of the women had baseline THC concentrations of <2 mcg/L; the other two had 5.8 and 15.8 mcg/L of THC in their milk at baseline. The average THC concentration in breastmilk was 53.5 mcg/L (median 27.6 mcg/L; range 8.4 to 186.1 mcg/L), and the average peak THC concentration was 94 mcg/L (range 12.2 to 420.3 mcg/L) 1 hour after inhalation. The metabolites were not measurable (<0.097 mcg/L). The estimated daily THC intake for the infant was 8 mcg/kg, which corresponded to 2.5% (range 0.4 to 8.7%) of the weight-adjusted maternal dosage.[ HYPERLINK "" 13]Fifty women who reported using cannabis in the prior 14 days donated milk samples for analysis of THC and its major metabolites. Four women donated two samples each for a total of 54 samples. THC was detectable in 63% of the samples. The median concentration of THC was 9.47 mcg/L (range 1 to 323 mcg/L). Only 5 samples had measurable concentrations of 11-OH-THC (range 1.3 to 12.8 mcg/L) and 5 samples had measurable concentrations of cannabidiol (range 1.3 to 8.6 mcg/L). Samples collected 140 hours (about 6 days) or longer after reported use contained no detectable (<1 mcg/L) THC and the sample with the highest cannabidiol concentration contained no detectable THC. Of the 34 milk samples from mothers who reported using cannabis, the half-life of THC in milk was estimated to average about 27 hours.[14] Using the median value, the median infant THC dosage would be 1.4 mcg/kg daily.Twenty women in Oregon who admitted to using a cannabis product while breastfeeding their infants provided milk samples for analysis. The mothers reported using cannabis almost daily. Fifteen women provided milk samples at their infant’s 2-week and 2-month checkup and 5 provided a sample at only one of the visits for a total of 35 milk samples. All but one milk sample contained at least one cannabinoid. None of the mothers reported using a cannabidiol (CBD) product, but 13 had detectable CBD in breastmilk. Median (IQR) concentrations in milk were as follows: THC 27.5 (0.8 to 190.5) mcg/L; 11-OH-THC 1.4 (0.7 to 5.2) mcg/L; THC-COOH 1.9 (0.5-16.6) mcg/L; CBD 1.2 (0.5 to 17) mcg/L. Three patients using edible products had similar cannabinoid levels as those who smoked cannabis. Fourteen mothers reported an increase in use of cannabis between the 2-week and 2-month visit. Median breast milk THC concentrations were 16.7 mcg/L at visit 1 and 54.5 mcg/L at visit 2. The authors estimated that overall the breastfed infants received an average THC dose of 4.12 mcg/kg daily (range 0.52 to 123 mcg/kg daily) in milk.[ HYPERLINK "" 15]Seven women who used cannabis during pregnancy more than twice weekly, primarily by smoking, and were documented to be abstinent postpartum donated blood and milk levels 2 to 5 times weekly for 6 to 7 weeks. Maximum milk THC levels ranged from 2.8 to 26.1 mcg/L and the elimination half-life from milk averaged 17 days (range 12.2 to 21 days).[16]Infant Levels. The urine of 2 breastfed infants whose mothers smoked marijuana found none of the 9-carboxy-THC metabolite. One mother reported smoking marijuana once daily and the other reported smoking marijuana 7 to 8 times daily. Analysis of the feces of the latter mother's infant revealed a higher proportion of metabolites than THC, indicating that THC was probably absorbed from the milk, metabolized by the infant, and excreted in feces.[ HYPERLINK "" 10]Effects in Breastfed InfantsTwenty-seven mothers reported smoking marijuana during breastfeeding. Twelve of them smoked once a month or less, 9 smoked weekly, and 6 smoked daily. Six of their infants were compared at 1 year of age to the infants of mothers who did not smoke marijuana during pregnancy or breastfeeding. No differences were found in growth, or on mental and motor development.[ HYPERLINK "" 4]Sixty-eight infants whose mothers reported smoking marijuana during breastfeeding were compared to 68 matched control infants whose mothers did not smoke marijuana. The duration of breastfeeding varied, but the majority of infants were breastfed for 3 months and received less than 16 fluid ounces of formula daily. Motor development of the marijuana-exposed infants was slightly reduced in a dose-dependent (i.e., number of reported joints per week) manner at 1 year of age, especially among those who reported smoking marijuana on more than 15 days/month during the first month of lactation. No effect was found on mental development.[ HYPERLINK "" 3]A small, case-control study found that paternal marijuana smoking postpartum increased the risk of sudden infant death syndrome. In this study, too few nursing mothers smoked marijuana to form any conclusion.[ HYPERLINK "" 17]A study of women taking buprenorphine for opiate substitution during pregnancy and lactation found that 4 of the women were also using cannabis as evidenced by positive urine screens for THC between 29 and 56 days postpartum. One was also taking unprescribed benzodiazepines. One infant was exclusively breastfed and the other 3 were mostly breastfeeding with partial supplementation. Infants had no apparent drug-related adverse effects and showed satisfactory developmental progress.[ HYPERLINK "" 18]Fifty women who reported using cannabis in the prior 14 days donated milk samples for analysis of THC and its major metabolites. THC was detectable in 66% of the samples and below the limit of quantification in 32% of samples. Preliminary evidence found no differences in infant adverse reactions, postnatal growth, or neurodevelopmental outcomes were found between the groups with quantifiable and nonquantifiable THC in breastmilk.[ HYPERLINK "" 19]Effects on Lactation and BreastmilkAcute one-time marijuana smoking suppresses serum concentrations of luteinizing hormone and prolactin in nonpregnant, nonlactating women.[20-22] The effects of long-term use is unclear, with some studies finding no effect on serum prolactin.[23-25] However, hyperprolactinemia has been reported in some chronic cannabis users,[26-28] and galactorrhea and hyperprolactinemia were reported in a woman who smoked marijuana for over 1 year.[28] The prolactin level in a mother with established lactation may not affect her ability to breastfeed.Of 258 mothers who reported smoking marijuana during pregnancy, 27 who had smoked marijuana during breastfeeding were followed-up at 1 year. No difference was found in the age of weaning between these mothers and 35 who reported not smoking marijuana during pregnancy or breastfeeding.[ HYPERLINK "" 4]The US state of Colorado legalized medical cannabis in 2001 and recreational cannabis in 2012. A cross-sectional survey conducted in Colorado in 2014 and 2015 found that both prenatal and postnatal cannabis use were associated with a shorter duration of breastfeeding. Among women who reported using cannabis during pregnancy, 64% breastfed for 9 or more weeks compared with 78% of women who did not use cannabis during pregnancy. Among women who reported postpartum cannabis use, 58% breastfed for 9 or more weeks compared with 79% of women who did not use cannabis postpartum. Both differences were statistically significant.[ HYPERLINK "" 29]A study using a database of 4969 postpartum women found that those who reported using marijuana were more likely to smoke cigarettes, experience postpartum depressive symptoms, and breastfeed for less than 8 weeks.[ HYPERLINK "" 30] Tobacco smoking is known to decrease the duration of breastfeeding, so the effect of marijuana is not clear. Most of the women who smoked marijuana postpartum also used it during pregnancy.NexiumDrug Levels and EffectsSummary of Use during LactationEsomeprazole is the S-enantiomer of the proton-pump inhibitor, omeprazole. Limited information indicates that maternal doses of 10 mg daily produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants.Drug LevelsMaternal Levels. A woman with rheumatoid arthritis was treated with oral esomeprazole 10 mg (0.17 mg/kg), prednisone 2.5 mg and sulfasalazine 1 gram once daily as well as injections of certolizumab pegol 200 mg every 2 weeks. Milk samples were measured several times during the first 4 days postpartum at 0.7, 4, and 8.2 hours after various doses, milk levels were 10.5 mcg/L, 19.6 mcg/L and 3 mcg/L, respectively. At 8, 10.5 and 19.4 hours after various doses, the drug was undetectable (<0.1 mcg/L) in milk. Using the highest measured level of 19.6 mcg/L, the authors calculated that a fully breastfed infant would receive a dose of 0.003 mg/kg daily, which would result in a maximum weight-adjusted dose of 1.8% of the mothers dose.[ HYPERLINK "" 1]Infant Levels. A woman with rheumatoid arthritis was treated with oral esomeprazole 10 mg (0.17 mg/kg) once daily. Her infant was about 50% breastfed and 50% formula fed. At 12.5 hours after the dose on the day of the infant’s birth, the cord blood level was 14.8 mcg/L, representing placental passage. By 23.2 hours after the mother’s previous dose (12 hours postpartum), esomeprazole was undetectable (<0.1 mcg/L) in the infant’s serum.[ HYPERLINK "" 1]Effects in Breastfed InfantsOne mother taking omeprazole 20 mg daily orally pumped and discarded her milk once each day 4 hours after her morning dose. She breastfed her infant the remainder of the day for 3 months before weaning. The infant remained well at 12 months of age.[ HYPERLINK "" 2]A woman with rheumatoid arthritis was treated with oral esomeprazole 10 mg, prednisone 2.5 mg and sulfasalazine 1 gram once daily as well as injections of certolizumab pegol 200 mg every 2 weeks. Her infant was about 50% breastfed and 50% formula fed. The infant had no detectable drug-related adverse effects.[ HYPERLINK "" 1]Effects on Lactation and BreastmilkOmeprazole (the racemic form) has been reported to cause gynecomastia in several men and a retrospective claims database study in the United States found that users of proton pump inhibitors had an increased risk of gynecomastia.[ HYPERLINK "" 3,4]One woman developed elevated serum prolactin and estradiol with bilateral galactorrhea one week after starting esomeprazole 40 mg once daily for reflux esophagitis. The galactorrhea disappeared 3 days after discontinuing esomeprazole and prolactin and estradiol returned to normal 7 days after discontinuation. One month later, the patient restarted esomeprazole and again developed bilateral galactorrhea. She was switched to lansoprazole with no galactorrhea developing.[ HYPERLINK "" 5] The prolactin level in a mother with established lactation may not affect her ability to breastfeed.Alternate Drugs to ConsiderAntacids, Cimetidine, Famotidine, Omeprazole, Pantoprazole, SucralfateBenadrylDiphenhydramine (Benadryl), which is frequently prescribed for children, is also excreted in breast milk in small quantities. Either of these medications can cause lethargy or irritability in infants. To reduce the risk to the infant, the mother can take these medications immediately after breastfeeding.Drug Levels and EffectsSummary of Use during LactationSmall, occasional doses of diphenhydramine would not be expected to cause any adverse effects in breastfed infants. Larger doses or more prolonged use may cause effects in the infant or decrease the milk supply, particularly in combination with a sympathomimetic such as pseudoephedrine or before lactation is well established. Single bedtime doses after the last feeding of the day may be adequate for many women and will minimize any effects of the drug. The nonsedating antihistamines are preferred alternatives.Drug LevelsMaternal Levels. One old study that used a biologic assay system reported that after a 100 mg intramuscular dose of diphenhydramine in four women, drug levels in milk were undetectable in two and 42 and 100 mcg/L in two others at one hour after the dose. Five hours after the dose, milk levels were undetectable in two women and 20 and 100 mcg/L in two others.[ HYPERLINK "" 1] No studies using modern assay methods have been reported.Infant Levels. Relevant published information was not found as of the revision date.Effects in Breastfed InfantsIn one telephone follow-up study, mothers reported irritability and colicky symptoms 10% of infants exposed to various antihistamines and drowsiness was reported in 1.6% of infants. None of the reactions required medical attention. In this study, drowsiness was reported in 1 infant of 12 exposed to diphenhydramine in breastmilk.[ HYPERLINK "" 2]Effects on Lactation and BreastmilkAntihistamines in relatively high doses given by injection can decrease basal serum prolactin in nonlactating women and in early postpartum women.[3,4] However, suckling-induced prolactin secretion is not affected by antihistamine pretreatment of postpartum mothers.[3] Whether lower oral doses of diphenhydramine have the same effect on serum prolactin or whether the effects on prolactin have any consequences on breastfeeding success have not been studied. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.One woman became dependent on dimenhydrinate (which is 55% diphenhydramine) during her first pregnancy and continued to take it in a dose of 150 mg (83 mg diphenhydramine) daily while she breastfed her infant for 3 months. The infant did well except for a febrile seizure at 2 years of age, which was probably unrelated to dimenhydrinate. During her second pregnancy, she took dimenhydrinate 300 mg (165 mg diphenhydramine) daily during the pregnancy and while breastfeeding her infant for 2 years.[ HYPERLINK "" 5]Alternate Drugs to ConsiderDesloratadine, Fexofenadine, LoratadineXanexDrug Levels and EffectsSummary of Use during LactationA safety scoring system finds alprazolam possible to use during breastfeeding.[ HYPERLINK "" 1] Because of reports of effects in infants, including sedation, alprazolam is probably not the best benzodiazepine for repeated use during nursing, especially with a neonate or premature infant. A shorter-acting benzodiazepine without active metabolites is preferred. After a single dose of alprazolam, there is usually no need to wait to resume breastfeeding.Drug LevelsMaternal Levels. Eight lactating women who averaged 11.8 weeks postpartum (range 6 to 28 weeks) were given a single 0.5 mg dose of alprazolam orally. Eleven breastmilk samples were obtained over the 36 hours after the dose. A mean peak alprazolam milk level of 3.7 mcg/L occurred at an average of 1.1 hours (range 0.47 to 3.8 hours) after the dose. The half-life of alprazolam in milk averaged 14.5 hours. The metabolites 4-hydroxyalprazolam and alpha-hydroxyalprazolam were not detected (<0.5 to 1 mcg/L) in milk. The authors calculated that an exclusively breastfed infant whose mother was taking alprazolam in the normal dosage range would receive a daily dosage of 0.5 to 5 mcg/kg or about 3% of the maternal weight-adjusted dosage.[2]A lactating woman was taking alprazolam and donated milk samples before a dose and 2 hours after a dose at day 3 postpartum and at 1 month postpartum. At 3 days postpartum, she was taking 0.8 mg daily. Her trough milk alprazolam concentration was 2.78 mcg/L and 2-hour milk level was 3.4 mcg/L. At 1 month postpartum, she was taking 1 mg daily and her 2-hour milk level was 5.42 mcg/L. No metabolites were detected in breastmilk.[ HYPERLINK "" 3]A woman who was taking an oral alprazolam dose of 2.4 mg daily donated milk samples at between 3 and 6 days postpartum. She had milk levels of 24.5 mcg/L at 2 hours after the dose and 23.8 mcg/L at 4 hours after the dose.[ HYPERLINK "" 4]Infant Levels. Relevant published information was not found as of the revision date.Effects in Breastfed InfantsIncreased infant irritability following withdrawal of breastfeeding occurred in a 1-week-old infant whose mother had taken alprazolam during pregnancy and continued to take it after delivery. This reaction probably indicates that there was sufficient alprazolam in breastmilk to prevent withdrawal. The authors reported correspondence with the manufacturer who stated that they had received spontaneous reports of infant withdrawal symptoms (crying, irritability and sleep disturbances) for 2 weeks in a 9-month-old exclusively breastfed infant after slow (over 3 weeks) maternal discontinuation of alprazolam (dosage unspecified).[5]In one telephone follow-up study of 5 infants (ages not stated) exposed to alprazolam during breastfeeding, 1 mother reported drowsiness in her infant. The reaction did not require medical attention.[ HYPERLINK "" 6]In a telephone follow-up study, 124 mothers who took a benzodiazepine while nursing reported whether their infants had any signs of sedation. About 5% of mothers were taking alprazolam. One mother who was taking sertraline 50 mg daily, zopiclone 2.5 mg about every 3 days as needed, and also took alprazolam 0.25 mg on 2 occasions, reported sedation in her breastfed infant.[ HYPERLINK "" 7]Effects on Lactation and BreastmilkUnlike other benzodiazepines, alprazolam can increase serum prolactin.[8,9] One woman developed galactorrhea, amenorrhea and elevated serum prolactin after taking 3 mg of sustained-release alprazolam and 5 to 6 mg of immediate-release alprazolam daily for several months for self-treatment of fear, poor sleep, palpitations and gastrointestinal discomfort. After slow discontinuation of alprazolam and institution of quetiapine and fluvoxamine, galactorrhea ceased after about one month, menses normalized after about 2 months, and serum prolactin decreased to a normal level.[ HYPERLINK "" 10] The prolactin level in a mother with established lactation may not affect her ability to breastfeed.Alternate Drugs to ConsiderLorazepam, Midazolam, OxazepamAcetaminophenAcetaminophen (Tylenol, Tempra) – is a recommended agent during breastfeeding.Drug Levels and EffectsSummary of Use during LactationAcetaminophen is a good choice for analgesia, and fever reduction in nursing mothers. Amounts in milk are much less than doses usually given to infants. Adverse effects in breastfed infants appear to be rare.Drug LevelsMaternal Levels. A single oral dose of 650 mg of acetaminophen was given to 12 nursing mothers who were 2 to 22 months postpartum. Peak milk levels of 10 to 15 mg/L occurred between 1 and 2 hours after the dose in all patients. Acetaminophen was undetectable (<0.5 mg/L) in all mothers 12 hours after the dose. The authors calculated that an infant who ingested 90 mL of breastmilk every 3 hours would receive an average of 0.88 mg of acetaminophen or 0.14% (range 0.04 to 0.23%) of the mother's absolute dosage.[1] Using data from this study, an infant would receive a maximum of about 2% of the maternal weight-adjusted dosage.Three women took a single 500 mg dose of acetaminophen. Peak milk levels averaging 4.2 mg/L occurred within 2 hours after the dose.[2] Using data from this study, an infant would receive a maximum of about 3.6% of the maternal weight-adjusted dosage.Four women who were 2 to 8 months postpartum were given a single 1 gram dose of acetaminophen. Peak milk levels occurred between 1 and 2.5 hours after the dose. The authors estimated that a breastfed infant would receive an average of 1.1% and a maximum of 1.8% of the maternal weight-adjusted dosage. This dose is about 0.5% of the lowest recommended infant dose of acetaminophen.[3]Infant Levels. No acetaminophen was detected in the urine of 12 breastfed infants aged 2 to 22 months after maternal ingestion of 650 mg of acetaminophen.[1]Urine was collected for 1 to 3.5 hours after nursing in 6 infants aged 2 to 6 days whose mothers received 1 to 2 grams of acetaminophen 2 to 4 hours before nursing their infant. Infants excreted an average of 401 mcg of acetaminophen and its metabolites in urine during the collection interval. These neonates excreted a greater percentage of drug as acetaminophen and much less as the sulfate metabolite than adults.[3]Effects in Breastfed InfantsA maculopapular rash on the upper trunk and face of a 2-month-old infant was probably caused by acetaminophen in breastmilk. The rash occurred after 2 days of therapy in the mother at a dose of 1 gram at bedtime. It subsided when the drug was discontinued and recurred 2 weeks later after another acetaminophen dose of 1 gram was taken by the mother.[4]Two papers report 14 women who breastfed after taking acetaminophen or its prodrug phenacetin with no adverse effects to their infants.[1][5]In a telephone follow-up study, mothers reported no side effects among 43 infants exposed to acetaminophen in breastmilk.[6]Two clinicians speculated that breastmilk exposure to acetaminophen during breastfeeding might be a risk factor for asthma and wheezing in the breastfed infants based on their personal observations.[7] However, these observations were uncontrolled and cannot be considered to be valid proof of an association.[8]Effects on Lactation and BreastmilkRelevant published information was not found as of the revision date.Alternate Drugs to ConsiderIbuprofenIbuprofenIbuprofen (Motrin) is a nonsteroidal antiinflammatory medication.Of the nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen (Motrin) is the preferred choice because it has poor transfer into milk and has been well-studied in children. Long half-life NSAIDs such as naproxen (Naprosyn), sulindac (Clinoril) and piroxicam (Feldene) can accumulate in the infant with prolonged use.7Summary of Use during LactationBecause of its extremely low levels in breastmilk, short half-life and safe use in infants in doses much higher than those excreted in breastmilk, ibuprofen is a preferred choice as an analgesic or antiinflammatory agent in nursing mothers.Drug LevelsMaternal Levels. Two early studies attempted measurement of ibuprofen in milk. In one, the patient's dose was 400 mg twice daily, while in the second study of 12 patients, the dose was 400 mg every 6 hours. Ibuprofen was undetectable in breastmilk in both studies (<0.5 and 1 mg/L, respectively).[ HYPERLINK "" 1,2]A later study using a more sensitive assay found ibuprofen in the breastmilk of one woman who took 6 doses of 400 mg orally over 42.5 hours. A milk ibuprofen level of 13 mcg/L was detected 30 minutes after the first dose. The highest level measured was 180 mcg/L about 4 hours after the third dose, 20.5 hours after the first dose. The authors estimated that the infant would receive about 17 mcg/kg daily (100 mcg daily) with the maternal dose of approximately 1.2 grams daily. This dose represents 0.0008% of the maternal weight-adjusted dosage[ HYPERLINK "" 3] and 0.06% of the commonly accepted infant dose of 30 mg/kg daily (10 mg/kg every 8 hours).Single milk samples were taken from 13 women between 1.5 and 8 hours after the third dose of ibuprofen in a daily dosage regimen averaging 1012 mg daily (range 400 to 1200 mg daily). Of the 13 milk samples analyzed, the mean milk concentration was 361 mcg/L (range 164 to 590 mcg/L). The mean weight-adjusted percentage of the maternal dosage (relative infant dosage [RID]) was estimated to be <0.38%; however, the RID varied with the time postpartum and the milk protein content. The RID was highest in the colostral phase when the milk protein content was the highest (RID 0.6%). The estimated mean dosage for a fully breastfed infants was 68 mcg/kg daily or 0.2% of a pediatric dosage.[ HYPERLINK "" 4]Infant Levels. Relevant published information was not found as of the revision date.Effects in Breastfed InfantsAt least 23 cases are reported in the literature in which infants (ages not stated) were breastfed during maternal ibuprofen use with no adverse effects reported.[ HYPERLINK "" 1,3,5]Effects on Lactation and BreastmilkRelevant published information was not found as of the revision date.Alternate Drugs to ConsiderAcetaminophen, Flurbiprofen, Indomethacin, Naproxen, PiroxicamZithromax (azithromycin)Summary of Use during LactationBecause of the low levels of azithromycin in breastmilk and use in infants in higher doses, it would not be expected to cause adverse effects in breastfed infants. Monitor the infant for possible effects on the gastrointestinal flora, such as vomiting, diarrhea, candidiasis (thrush, diaper rash). Unconfirmed epidemiologic evidence indicates that the risk of infantile hypertrophic pyloric stenosis might be increased by maternal use of macrolide antibiotics during the first two weeks of breastfeeding, but others have questioned this relationship. A single dose of azithromycin given during labor to women who were nasal carriers of pathogenic Staphylococcus and Streptococcus reduced the counts of these bacteria in breastmilk in one study.Drug LevelsMaternal Levels. A woman who was 1 day postpartum was given 1 g of azithromycin orally. Forty-eight hours later her milk azithromycin was 0.64 mg/L. An oral regimen of 500 mg daily for 5 days was started and more milk samples were obtained. One hour after the first dose, breastmilk contained 1.3 mg/L and 30 hours after the third dose milk contained 2.8 mg/L.[ HYPERLINK "" 1] Because of the slow clearance and accumulation of azithromycin, it is difficult to interpret these milk levels. The dose that the infant would receive in milk would gradually increase for several days because maternal blood levels would increase until steady-state had been reached. If the level of 2.8 mg/L is used as an approximate trough level, an exclusively breastfed infant would receive a minimum of 0.42 mg/kg daily compared to the dose of 5 to 10 mg/kg daily used in infants of 6 months and over.In a study of 30 women given azithromycin 500 mg intravenously 15, 30 or 60 minutes prior to incision for cesarean section, 8 women extracted breastmilk by pump. Breastmilk (colostrum) samples were obtained between 12 and 48 hours after the dose. Azithromycin persisted in breastmilk up to 48 hours after a dose with a median breastmilk concentration of 1713 mcg/L at a median of 30.7 hours after the dose. A computer model was constructed and the calculated median half-life in breastmilk was 15.6 hours, which was longer than the maternal serum half-life of 6.7 hours. Using the model, the authors calculated that with continuous administration of 500 mg every 12 hours, steady-state would occur in 3 days and an exclusively breastfed infant would receive 0.1 mg/kg daily.[ HYPERLINK "" 2]Breastmilk azithromycin concentrations were measured in 20 Gambian women after receiving a single 2 gram oral dose of azithromycin during labor. Breastmilk samples were collected on days 2 and 6 postpartum as well as 2 and 4 weeks postpartum (80 samples total, of which 78 were used). Milk concentrations were entered into a previously existing population model of azithromycin pharmacokinetics in pregnant women. The median cumulative infant dosage over the first 28 days postpartum was estimated to be 3.9 mg/kg (0.6 mg/kg daily) for the single 2 gram maternal dose. The authors also simulated a maternal dosage regimen of 1 gram daily for 3 days and estimated an infant dosage of 7.8 mg/kg (1.2 mg/kg daily). These values translate to a weight-adjusted dosage of 2.2% and 2.9% of the maternal dosage, respectively. The median absolute dosages are considerably less than the reported infant dosages of 50 to 60 mg/kg; however, simulations indicated that the maximum dosage that an infant might receive is 32 and 63 mg/kg, respectively, of the standard infant dosage.[ HYPERLINK "" 3]Infant Levels. Relevant published information was not found as of the revision date.Effects in Breastfed InfantsA cohort study of infants diagnosed with infantile hypertrophic pyloric stenosis found that affected infants were 2.3 to 3 times more likely to have a mother taking a macrolide antibiotic during the 90 days after delivery. Stratification of the infants found the odds ratio to be 10 for female infants and 2 for male infants. All of the mothers of affected infants nursed their infants. Most of the macrolide prescriptions were for erythromycin, but only 7% were for azithromycin. However, the authors did not state which macrolide was taken by the mothers of the affected infants.[ HYPERLINK "" 4]A retrospective database study in Denmark of 15 years of data found a 3.5-fold increased risk of infantile hypertrophic pyloric stenosis in the infants of mothers who took a macrolide during the first 13 days postpartum, but not with later exposure. The proportion of infants who were breastfed was not known, but probably high. The proportion of women who took each macrolide was also not reported.[ HYPERLINK "" 5]A study comparing the breastfed infants of mothers taking amoxicillin to those taking a macrolide antibiotic found no instances of pyloric stenosis. However, most of the infants exposed to a macrolide in breastmilk were exposed to roxithromycin. Only 10 of the 55 infants exposed to a macrolide were exposed to azithromycin. Adverse reactions occurred in 12.7% of the infants exposed to macrolides which was similar to the rate in amoxicillin-exposed infants. Reactions included rash, diarrhea, loss of appetite, and somnolence.[ HYPERLINK "" 6]Eight women who were given azithromycin 500 mg intravenously 15, 30 or 60 minutes prior to incision for cesarean section breastfed their newborn infants. No adverse events were noted in their infants.[ HYPERLINK "" 2]Two meta-analyses failed to demonstrate a relationship between maternal macrolide use during breastfeeding and infantile hypertrophic pyloric stenosis.[ HYPERLINK "" 7,8]Effects on Lactation and BreastmilkIn a double-blind, controlled study in Gambia, women who were nasopharyngeal carriers of Staphylococcus aureus, Streptococcus pneumoniae or group B streptococcus were given a single 2 gram dose of azithromycin during labor. Milk samples from women who received azithromycin had 9.6% prevalence of carriage of the organisms compared to 21.9% in women who received placebo. Nasopharyngeal carriage in mothers and infants was also reduced on day 6 postpartum.[ HYPERLINK "" 9]Alternate Drugs to ConsiderClarithromycin, ErythromycinOther anxiety medication: Paroxetine (Paxil)Drug Levels and EffectsSummary of Use during LactationBecause of the low levels of paroxetine in breastmilk, amounts ingested by the infant are small and paroxetine has not been detected in the serum of most infants tested. Occasional mild side effects have been reported, especially in the infants of mothers who took paroxetine during the third trimester of pregnancy, but the contribution of the drug in breastmilk is not clear. Most authoritative reviewers consider paroxetine one of the preferred antidepressants during breastfeeding.[ HYPERLINK "" 1-7] Occasional mild side effects such as insomnia, restlessness and increased crying have been reported in breastfed infants. Mothers taking an SSRI during pregnancy and postpartum may have more difficulty breastfeeding, although this might be a reflection of their disease state.[ HYPERLINK "" 8] These mothers may need additional breastfeeding support. Breastfed infants exposed to an SSRI during the third trimester of pregnancy have a lower risk of poor neonatal adaptation than formula-fed infants.Drug LevelsMaternal Levels. In a pooled analysis of serum levels from published studies and 3 unpublished cases, the authors found 50 mothers taking an average daily dosage of 21 mg (range 10 to 50 mg) had an average milk paroxetine level of 28 mcg/L (range 0 to 153 mcg/L).[1] Using the average dosage and milk level data from this paper, an exclusively breastfed infant would receive an estimated 1.2% of the maternal weight-adjusted dosage of paroxetine.From data in 6 mothers taking paroxetine in an average daily dosage of 20 mg (range 10 to 30 mg), the authors estimated that an exclusively breastfed infant would receive 1.4% of the maternal weight-adjusted dosage.[ HYPERLINK "" 9]At 2 months postpartum, 19 mothers taking an average of 25 mg of paroxetine daily had average milk levels of 13.5 mcg/L at random times after the previous dose. The authors estimated that an exclusively breastfed infant would receive 0.02 mg/kg of paroxetine daily.[ HYPERLINK "" 10]A woman had taken paroxetine 15 mg daily during pregnancy. She did not receive a dose in the 22.75 hours before delivery or on the day of delivery. She resumed paroxetine 15 mg daily 24 hours postpartum. At 3.75 hours after the third postpartum dose, her breastmilk paroxetine level was 371 mcg/L.[ HYPERLINK "" 11]Four nursing mothers who were 6.5 to 18.5 weeks postpartum were taking paroxetine in doses of 12.5 to 60 mg daily in addition to quetiapine for major depression postpartum. Breastmilk samples obtained at various times after the dose had undetectable (<9.9 mcg/L) levels of paroxetine in 3 mothers. One mother who was taking 50 mg daily had a milk paroxetine level of 255 mcg/L.[ HYPERLINK "" 12]A woman taking paroxetine 20 mg daily had a breastmilk paroxetine concentration below the lower limit of quantification (<20 mcg/L) at a time that was not stated.[13]A nursing mother was taking paroxetine 20 mg daily. Foremilk and hindmilk samples taken at 4 weeks postpartum, 7 hours after a dose contained 16 mcg/L and 24 mcg/L, respectively.[ HYPERLINK "" 14]Five women treated with paroxetine 7 to 25 mg daily during the third trimester of pregnancy and during breastfeeding provided trough milk samples during the first week postpartum. Paroxetine was undetectable (<5 mcg/L) in the milk of 2 women taking 10 mg daily. In the other 3 women, milk levels ranged from 5.9 to 32.9 mcg/L, with calculated weight-adjusted percentage of maternal dosages ranging from 1.1 to 3.2%. These values might be inaccurate because of the timing of milk sample collection.[ HYPERLINK "" 15]Infant Levels. Sixteen breastfed infants (2 about 50% breastfed; the others 95% or more breastfed) aged 6 to 13 weeks had undetectable (<1 mcg/L) paroxetine serum levels during maternal therapy with paroxetine in an average daily dosage of 18.75 mg (range 5 to 30 mg).[ HYPERLINK "" 16]In a pooled analysis of 40 mother-infant pairs from published and unpublished cases, the authors found that no infants had measurable paroxetine plasma levels.[ HYPERLINK "" 1]In 6 breastfed (extent not stated) infants aged 2 to 33 weeks whose mothers were taking paroxetine in an average daily dosage of 20 mg (range 10 to 30 mg), paroxetine was undetectable (<1.6 mcg/L) in all of the infants' serum. One mother taking 20 mg daily and her infant were both poor metabolizers (homozygous for CYP2D6*4), yet no paroxetine was detectable in infant serum.[ HYPERLINK "" 9]At 2 months postpartum, the breastfed infants of 19 mothers taking an average of 25 mg of paroxetine daily had an average serum paroxetine level of 0.95 mcg/L which was 5% of the maternal serum level.[ HYPERLINK "" 10]Effects in Breastfed InfantsAgitation and difficulty feeding in one infant (age and other details not reported) that were possibly related to paroxetine in breastmilk were reported to the Australian Adverse Drug Reaction Advisory Committee.[ HYPERLINK "" 17]In a controlled cohort study of mothers who took paroxetine during pregnancy (diagnoses not reported), 36 mothers took paroxetine during the third trimester and breastfed their infants. Of these, 8 reported side effects in their infants including alertness (6), constipation (3), sleepiness (1), and irritability (1). There were no reports of side effects in the control group of mothers who breastfed and did not use paroxetine in the third trimester or during nursing. The relative contribution of transplacental and breastmilk acquisition of the drug could not be determined.[ HYPERLINK "" 18]In a study comparing the infants of mothers who took an SSRI during pregnancy for major depression with the infants of depressed mothers who did not take an SSRI, mental development and most motor development was normal at follow-up averaging 12.9 months in both groups. Four of the treated mothers took paroxetine in doses averaging 28.6 mg daily for an average of 7.8 months while breastfeeding (extent not stated) their infants. Psychomotor development was slightly delayed compared to controls, but the contribution of breastfeeding to abnormal development could not be determined.[ HYPERLINK "" 19]A prospective cohort study evaluated 27 infants whose mothers took paroxetine (diagnoses not reported) at an average dose of 20.7 mg daily for at least 2 weeks during breastfeeding (extent not stated). Two control groups consisted of two groups of mothers who neither breastfed nor took an SSRI. All but 7 of the 27 mothers took paroxetine during some part of pregnancy. Weight at 3 months was less in the paroxetine group, but multivariate analysis indicated that maternal paroxetine use was not the determining factor. Weights at 6 and 12 months were not different from the control groups and other developmental milestones were reached at the normal times. One of the paroxetine-exposed infants (age not stated) was reported by the mother to be irritable.[ HYPERLINK "" 20]Fifteen mothers who took an average paroxetine dosage of 20.4 mg daily for depression or anxiety starting no later than 4 weeks postpartum, breastfed their infants exclusively for 4 months and at least 50% during months 5 and 6. Their infants had 6-month weight gains that were normal according to national growth standards and mothers reported no abnormal effects in their infants.[ HYPERLINK "" 21]In 6 breastfed (extent not stated) infants aged 2 to 33 weeks whose mothers were taking paroxetine 10 to 30 mg daily, no adverse reactions were noted clinically at the time of the study.[9]An infant born to a mother taking paroxetine had serum paroxetine levels about one-third that of the mother's at birth. The infant was a genetic poor metabolizer which apparently was the cause of the high serum levels. Although the infant had symptoms attributed to paroxetine obtained in utero, the mother continued taking paroxetine 30 mg daily and breastfeeding (extent not stated). At 4 months of age, the infant had gained weight normally and had no evidence of neurological side effects.[ HYPERLINK "" 22]An 18-month-old infant with a 2-week history of vomiting was found to have hypokalemia, hypochloremic alkalosis and mild dehydration. The infant had been admitted twice previously 2 and 3 months before with a similar picture. Serum renin and aldosterone were normal. The infant's mother had been taking paroxetine 40 mg daily for about 1 year for depression and breastfeeding the infant (extent not stated). Paroxetine was detected, but not quantified, in the mother's breastmilk and infant's serum. Breastfeeding was discontinued and the infant was thriving 6 weeks later with a normal metabolic profile. The authors attributed the infant's metabolic abnormalities to paroxetine-induced syndrome of inappropriate secretion of antidiuretic hormone.[ HYPERLINK "" 23] The reaction was possibly caused by paroxetine in breastmilk, but strong evidence was lacking and other possible causes cannot be ruled out.A small study compared the reaction to pain in infants of depressed mothers who had taken an SSRI during pregnancy alone or during pregnancy and nursing, to a control group of unexposed infants of nondepressed mothers. Infants exposed to an SSRI either prenatally alone or prenatally and postnatally via breastmilk had blunted responses to pain compared to control infants. Nineteen of the 30 infants were exposed to paroxetine. Because there was no control group of depressed, nonmedicated mothers, an effect due to maternal behavior caused by depression could not be ruled out. The authors stressed that these findings did not warrant avoiding drug treatment of depression during pregnancy or avoiding breastfeeding during SSRI treatment.[ HYPERLINK "" 10]One study of side effects of SSRI antidepressants in nursing mothers found no adverse reactions that required medical attention among 3 infants whose mother was taking paroxetine. No specific information on maternal paroxetine dosage, extent of breastfeeding or infant age was reported.[ HYPERLINK "" 24]A nursing mother with bipolar disorder began taking 20 mg of paroxetine at 4 months postpartum and was then started on quetiapine 200 mg twice daily at 6 months postpartum. She breastfed regularly (extent not stated) and no obvious adverse effects were noted in the infant.[ HYPERLINK "" 25]Four nursing mothers who were 6.5 to 18.5 weeks postpartum were taking paroxetine in doses of 12.5 to 60 mg daily in addition to quetiapine for major depression postpartum. Their breastfed infants' development were tested at 9 to 18 months of age with the Bayley Scales. Measurements were slightly low on the mental and psychomotor development scale in one infant and on the mental development scale in another; both infants had undetectable (<9.9 mcg/L) serum paroxetine levels. All other infants had scores that were within normal limits. The authors concluded that the low scores of the two infants were probably not caused by the drugs received by the infants in breastmilk.[ HYPERLINK "" 12]An uncontrolled online survey compiled data on 930 mothers who nursed their infants while taking an antidepressant. Infant drug discontinuation symptoms (e.g., irritability, low body temperature, uncontrollable crying, eating and sleeping disorders) were reported in about 10% of infants. Mothers who took antidepressants only during breastfeeding were much less likely to notice symptoms of drug discontinuation in their infants than those who took the drug in pregnancy and lactation.[ HYPERLINK "" 26]A cohort of 247 infants exposed to an antidepressant in utero during the third trimester of pregnancy were assessed for poor neonatal adaptation (PNA). Of the 247 infants, 154 developed PNA. Infants who were exclusively given formula had about 3 times the risk of developing PNA as those who were exclusively or partially breastfed. Forty-nine of the infants were exposed to paroxetine in utero.[ HYPERLINK "" 27]A retrospective study of 42 nursing mothers who had been seen at a psychiatric outpatient facility, followed for at least 8 weeks, and prescribed paroxetine found that adverse effects were reported in 5 (12%) of their infants. One mother was taking 10 mg daily and 4 mothers were taking 20 mg daily. The most commonly reported adverse events in the infants were insomnia and restlessness; constant crying and poor feeding were less commonly reported. All of the adverse effects developed within the first 2 weeks after initiation of maternal treatment and disappeared within the 3 days after drug discontinuation. Adverse effects disappeared in one infant after reducing the maternal dosage from 20 mg daily to 10 mg daily. There was no difference in prevalence of adverse effects between these infants and those in the same study whose mothers were prescribed sertraline.[ HYPERLINK "" 28]A mother who was exclusively breastfeeding a 2-month-old infant began taking paroxetine 20 mg daily for depression. After paroxetine was begun, the mother reported severe constipation in the infant, which resolved within 2 days after discontinuing paroxetine with no treatment. No abnormalities were seen on physical examination or laboratory tests. The infant had previously developed agitation and sleeplessness with maternal sertraline use. The infant subsequently tolerated maternal citalopram use.[ HYPERLINK "" 29]Five women were treated with paroxetine 7 to 25 mg daily during the third trimester of pregnancy and during breastfeeding. Pediatric evaluations including neurologic assessments and brain ultrasound were conducted during the first 24 hours postpartum. Further follow-up was conducted at 6 or more months of age. Infant clinical status was comparable to unexposed infants from the same pediatric department.[ HYPERLINK "" 15]A case series reported 8 women who received paroxetine 20 mg and mirtazapine 15 mg daily for various psychiatric disorders. The women breastfed (extent not stated) their infants who averaged 4.3 weeks of age. Follow-up of the infants after 3 to 6 weeks when mirtazapine was discontinued found one infant who experienced restlessness after 5 days of therapy according to the mother. Discontinuation of mirtazapine had no effect, but the symptoms disappeared when paroxetine was discontinued. No other infants had other adverse effects observed.[ HYPERLINK "" 30]Effects on Lactation and BreastmilkParoxetine can cause galactorrhea, usually with increased prolactin levels, in nonpregnant, nonnursing patients.[31-39] In a study of cases of hyperprolactinemia and its symptoms (e.g., gynecomastia) reported to a French pharmacovigilance center, paroxetine was found to have a 3.1-fold increased risk of causing hyperprolactinemia compared to other drugs.[40] The prolactin level in a mother with established lactation may not affect her ability to breastfeed.In a small prospective study, 8 primiparous women who were taking a serotonin reuptake inhibitor (SRI; 3 taking fluoxetine and 1 each taking citalopram, duloxetine, escitalopram, paroxetine or sertraline) were compared to 423 mothers who were not taking an SRI. Mothers taking an SRI had an onset of milk secretory activation (lactogenesis II) that was delayed by an average of 16.7 hours compared to controls (85.8 hours postpartum in the SRI-treated mothers and 69.1 h in the untreated mothers), which doubled the risk of delayed feeding behavior in the untreated group. However, the delay in lactogenesis II may not be clinically important, since there was no statistically significant difference between the groups in the percentage of mothers experiencing feeding difficulties after day 4 postpartum.[ HYPERLINK "" 41]A case control study compared the rate of predominant breastfeeding at 2 weeks postpartum in mothers who took an SSRI antidepressant throughout pregnancy and at delivery (n = 167) or an SSRI during pregnancy only (n = 117) to a control group of mothers who took no antidepressants (n = 182). Among the two groups who had taken an SSRI, 33 took citalopram, 18 took escitalopram, 63 took fluoxetine, 2 took fluvoxamine, 78 took paroxetine, and 87 took sertraline. Among the women who took an SSRI, the breastfeeding rate at 2 weeks postpartum was 27% to 33% lower than mother who did not take antidepressants, with no statistical difference in breastfeeding rates between the SSRI-exposed groups.[ HYPERLINK "" 42]An observational study looked at outcomes of 2859 women who took an antidepressant during the 2 years prior to pregnancy. Compared to women who did not take an antidepressant during pregnancy, mothers who took an antidepressant during all 3 trimesters of pregnancy were 37% less likely to be breastfeeding upon hospital discharge. Mothers who took an antidepressant only during the third trimester were 75% less likely to be breastfeeding at discharge. Those who took an antidepressant only during the first and second trimesters did not have a reduced likelihood of breastfeeding at discharge.[ HYPERLINK "" 43] The antidepressants used by the mothers were not specified.A retrospective cohort study of hospital electronic medical records from 2001 to 2008 compared women who had been dispensed an antidepressant during late gestation (n = 575; paroxetine n = 53) to those who had a psychiatric illness but did not receive an antidepressant (n = 1552) and mothers who did not have a psychiatric diagnosis (n = 30,535). Women who received an antidepressant were 37% less likely to be breastfeeding at discharge than women without a psychiatric diagnosis, but no less likely to be breastfeeding than untreated mothers with a psychiatric diagnosis.[ HYPERLINK "" 44]Alternate Drugs to ConsiderNortriptyline, SertralineOther depression medication: SertralineDrug Levels and EffectsSummary of Use during LactationBecause of the low levels of sertraline in breastmilk, amounts ingested by the infant are small and is usually not detected in the serum of the infant, although the weakly active metabolite norsertraline (desmethylsertraline) is often detectable in low levels in infant serum. Rarely, preterm infants with impaired metabolic activity might accumulate the drug and demonstrate symptoms similar to neonatal abstinence. Most authoritative reviewers consider sertraline a preferred antidepressants during breastfeeding.[1-9] Mothers taking an SSRI during pregnancy and postpartum may have more difficulty breastfeeding, although this might be a reflection of their disease state.[10] These mothers may need additional breastfeeding support. Breastfed infants exposed to an SSRI during the third trimester of pregnancy have a lower risk of poor neonatal adaptation than formula-fed infants.Drug LevelsSertraline is metabolized to norsertraline (desmethylsertraline), which has antidepressant activity of about 10% that of sertraline.Maternal Levels. In a pooled analysis of serum levels from published studies and 4 unpublished cases, the authors found that 15 mothers taking an average daily dosage of 83 mg (range 25 to 200 mg) had an average breastmilk sertraline level of 45 mcg/L (range 7 to 207 mcg/L).[1] Using the average dosage and milk level data from this paper, an exclusively breastfed infant would receive an estimated 0.5% of the maternal weight-adjusted dosage of sertraline.Twenty-six women who were an average of 15.8 weeks postpartum (range 5 to 36 weeks) and receiving an average of 124 mg sertraline daily for at least 14 days for severe depression were studied while breastfeeding with extensive milk and serum sampling over a 24-hour period. All milk samples had detectable sertraline (average 129 mcg/L; range 11 to 938 mcg/L) and norsertraline (average 258 mcg/L; range 20 to 1498 mcg/L). Drug concentrations were higher in the hindmilk than the foremilk. Analysis of milk sertraline data from 15 mothers who submitted complete sets of milk samples indicated that the peak concentration of the drug and metabolite occurred 8 to 9 hours after a dose. In these women, the concentration in milk correlated with serum concentration, but not daily dosage. The authors estimated that an exclusively breastfed infant would receive an average of 0.54% of the maternal weight-adjusted dosage and that pumping and discarding milk 8 to 9 hours after the mother's dose would decrease the infant's daily dosage by 17%.[11]From data in 6 mothers who were 5 to 34 weeks postpartum and taking sertraline in an average daily dosage of 64 mg (range 50 to 100 mg), the authors estimated that an exclusively breastfed infant would receive 0.9% of the maternal weight-adjusted dosage.[12]At 2 months postpartum, 4 mothers taking an average of 87.5 mg of sertraline daily had average milk levels of 26.4 mcg/L of sertraline and 29 mcg/L of norsertraline at random times after the previous dose. The authors estimated that an exclusively breastfed infant would receive 0.04 mg/kg of sertraline daily.[ HYPERLINK "" 13]The mother of a preterm infant was taking sertraline 150 mg daily during pregnancy and postpartum. Her breastmilk levels of sertraline and norsertraline on 3 days at random times averaged 201 and 358 mcg/L, respectively.[ HYPERLINK "" 14]One woman taking sertraline 25 mg daily had an average breastmilk sertraline concentration of 29 mcg/L at two times that were not stated. These values equated to an average infant dosage of 4.4 mcg/kg daily or 0.6% of the maternal weight-adjusted dosage. In the same paper, 3 women taking sertraline 50 mg daily had an average breastmilk sertraline concentration of 58 mcg/L at times that were not stated. These values equated to an average infant dosage of 8.7 mcg/kg daily or 1.2% of the maternal weight-adjusted dosage.[ HYPERLINK "" 15]A nursing mother was taking sertraline 50 mg daily. Foremilk and hindmilk samples taken at 4 weeks postpartum, 13 hours after a dose contained 26 mcg/L and 46 mcg/L, respectively.[ HYPERLINK "" 16]Nine women treated with sertraline 25 to 75 mg daily (7 were taking 50 mg daily) during the third trimester of pregnancy and during breastfeeding provided trough milk samples during the first week postpartum. Sertraline was undetectable (<5 mcg/L) in the milk of 1 woman taking 50 mg daily. In the other 8 women, milk levels ranged from 11.1 to 24.5 mcg/L, with calculated weight-adjusted percentage of maternal dosages ranging from 0.2 to 2.4%. These values might be inaccurate because of the timing of milk sample collection.[ HYPERLINK "" 17]Random milk samples were obtained from 6 women taking a median dosage of 50 mg (range 25 to 50 mg) of sertraline daily had a median sertraline milk concentration of 11.3 mcg/L (range 3.6 to 35.7 mcg/L). The authors calculated that this represents a median infant dosage of 1.6 (range 0.5 to 5.4) mcg/kg daily. No correlation was found between maternal dosage and milk sertraline level.[ HYPERLINK "" 18]Infant Levels. Of 30 breastfed infants (19 exclusively, 11 breastfed 50% or more) aged 6 to 13 weeks, 22 had undetectable (<1 mcg/L) sertraline serum levels during maternal therapy with sertraline dosages of 25 to 200 mg daily. Of the 8 infants who had detectable serum levels, their average sertraline serum level was 7.9 mcg/L. Their mothers, who were taking an average of 109 mg daily, had an average serum level of 52.8 mcg/L.[ HYPERLINK "" 19]In a pooled analysis of 53 mother-infant pairs from published and unpublished cases, the authors found that infants had an average of 2% (range 0 to 15%) of the sertraline plasma levels of the mothers'; 3 of the infants had a plasma level greater than 10% of the mothers' which was defined by the authors as being elevated.[1]Twenty-two breastfed (20 exclusively) infants with an average age of 16.6 weeks (range 4 to 28 weeks) whose mothers were receiving an average of 124 mg sertraline daily for at least 14 days for severe depression were studied. Infant serum levels were measured 2.2 hours (range 0.5 to 5 hours) after nursing. Four infants had detectable sertraline (>2 mcg/L) and 11 infants had detectable norsertraline in their serum with an average concentration of 22 mcg/L. One 11-week-old infant who was being treated for acute asthma with albuterol, inhaled corticosteroids and hydroxyzine had serum levels higher than its mother's, even though 4 other infants received higher doses of sertraline and norsertraline through milk.[ HYPERLINK "" 11]In 6 breastfed (extent not stated) infants aged 5 to 34 weeks whose mothers were taking sertraline in an average daily dosage of 15 mg (range 5 to 34 mg), sertraline and norsertraline were undetectable (<3.4 mcg/L).[12]In a study of mothers given sertraline prophylactically for recurrent postpartum depression, 7 opted to breastfeed. Infant serum was tested at 4 weeks of age with a maternal dosage of 50 mg daily. Sertraline (<2 mcg/L) and norsertraline (<12 mcg/L) were undetectable in the serum of any infant.[ HYPERLINK "" 20]In a study comparing sertraline to nortriptyline for postpartum depression, 13 infants were breastfed by mothers taking sertraline (dosage and extent of nursing were not stated). After a constant maternal sertraline dosage for at least 14 days, infants had their serum concentrations measured. The infants were an average of 5.9 weeks old at the time of serum sampling. Sertraline was not detectable (<2 mcg/L) in any of the infants' serum; norsertraline serum levels ranged from undetectable (<2 mcg/L) to 6 mcg/L.[ HYPERLINK "" 21]At 2 months postpartum, the breastfed infants of 4 mothers taking an average of 87.5 mg of sertraline daily had undetectable (<0.1 mcg/L) serum levels of sertraline and norsertraline.[13]A 33-week preterm infant was exclusively breastfed by a mother who was taking sertraline 150 mg daily during gestation, at delivery and postpartum. Because of symptoms similar to neonatal abstinence syndrome, the infant's serum concentrations of sertraline and desmethylsertraline were measured on day 5 postpartum. Levels were 13 and 52 mcg/L, respectively. Because of ongoing symptoms, breastfeeding was stopped on day 9 and the infant's serum levels reportedly dropped, although specific values were not presented in the paper. The infant was later found to have genetically intermediate metabolism of two of the CYP450 enzymes involved in sertraline metabolism.[ HYPERLINK "" 14]Authors of a metaanalysis on sertraline reported infant serum levels of sertraline and norsertraline in 25 infants who were breastfed by mothers taking sertraline. Ten of the infants were exclusively breastfed, two were 80% breastfed and the breastfeeding status of the others was not reported. Only two infants, both exclusively breastfed, had detectable serum sertraline levels of 2.1 and 2.4 mcg/L. The other infants had undetectable (<2 mcg/L) sertraline levels. Four other infants had detectable norsertraline levels ranging from 2.6 to 4.7 mcg/L. Sampling times were not reported.[ HYPERLINK "" 5]Effects in Breastfed InfantsTwo side effects possibly related to sertraline in breastmilk have been reported to the Australian Adverse Drug Reaction Advisory Committee. Benign neonatal sleep myoclonus occurred in one 4-month-old infant and agitation that spontaneously resolved was reported in another infant.[ HYPERLINK "" 22,23]None of 26 infants with an average age of 16.6 weeks (range 4 to 28 weeks) whose mothers were receiving an average of 124 mg sertraline daily had any detectable acute adverse reactions to sertraline in breastmilk. All had been breastfeeding for at least 3 weeks.[ HYPERLINK "" 11]Whole blood serotonin levels were measured in 14 mothers and their breastfed infants after 6 to 16 weeks of sertraline therapy. Maternal dosages ranged from 25 to 200 mg daily. Although maternal serotonin levels were decreased from 159 mcg/L to 19 mcg/L by sertraline therapy, infant serotonin levels averaged 227 mcg/L before and 224 mcg/L after maternal therapy. The authors concluded that these findings indicate that the amount of sertraline ingested by the infants was not sufficient to affect platelet serotonin uptake in breastfed infants. Platelets and neurons both have the same serotonin transporter, so this lack of effect was seen as indirect evidence of safety of sertraline use during breastfeeding. None of the infants experienced any adverse effects from sertraline in breastmilk, including 6 exclusively breastfed infants under 3 months of age.[ HYPERLINK "" 24]Twenty-five mothers who took an average sertraline dosage of 82.4 mg daily breastfed their infants exclusively for 4 months and breastfed at least 50% during months 5 and 6. Their infants had 6-month weight gains that were normal according to national growth standards and the mothers reported no abnormal effects in their infants.[ HYPERLINK "" 25]In 6 infants aged 5 to 34 weeks whose mothers were taking sertraline 50 to 100 mg daily, no adverse reactions were noted clinically at the time of the study.[ HYPERLINK "" 12]No adverse effects were seen in 7 infants who were 4 weeks old and whose mothers had been taking sertraline 50 mg daily since day 4 postpartum.[ HYPERLINK "" 20]One study of side effects of SSRI antidepressants in nursing mothers found no adverse reactions that required medical attention among 2 infants whose mother was taking sertraline. No specific information on maternal sertraline dosage, extent of breastfeeding or infant age was reported.[ HYPERLINK "" 26]A small study compared the reaction to pain in infants of depressed mothers who had taken an SSRI during pregnancy alone or during pregnancy and nursing, to a control group of unexposed infants of nondepressed mothers. Infants exposed to an SSRI either prenatally alone or prenatally and postnatally via breastmilk had blunted responses to pain compared to control infants. Four of the 30 infants were exposed to sertraline. Because there was no control group of depressed, nonmedicated mothers, an effect due to maternal behavior caused by depression could not be ruled out. The authors stressed that these findings did not warrant avoiding drug treatment of depression during pregnancy or avoiding breastfeeding during SSRI treatment.[ HYPERLINK "" 13]An uncontrolled online survey compiled data on 930 mothers who nursed their infants while taking an antidepressant. Infant drug discontinuation symptoms (e.g., irritability, low body temperature, uncontrollable crying, eating and sleeping disorders) were reported in about 10% of infants. Mothers who took antidepressants only during breastfeeding were much less likely to notice symptoms of drug discontinuation in their infants than those who took the drug in pregnancy and lactation.[ HYPERLINK "" 27]In a telephone follow-up study, 124 mothers who took a benzodiazepine while nursing reported whether their infants had any signs of sedation. One mother who was taking sertraline 50 mg daily, zopiclone 2.5 mg about every 3 days as needed, and also took alprazolam 0.25 mg on 2 occasions, reported sedation in her breastfed infant.[ HYPERLINK "" 28]A mother was taking sertraline 150 mg daily during gestation, at delivery and postpartum while exclusively breastfeeding her infant. Her preterm infant born by cesarean section at 33 weeks gestation developed hyperthermia, muscle tone regulation disorders, and high-pitched crying during the first 24 hours after birth. The symptoms worsened on the 4th day of life, but breastfeeding was continued. On day 5, the infant had serum concentrations of sertraline and its metabolite that are in the reported therapeutic range in adults. Breastfeeding was discontinued on day 9 postpartum and the infant's symptoms dissipated, serum drug levels decreased and the infant thrived over several months. The infant was later found to have genetically intermediate metabolism of two of the CYP450 enzymes involved in sertraline metabolism. The authors attributed the infant's symptoms to serotonergic overstimulation caused by persistently high sertraline levels from breastfeeding and reduced metabolism.[ HYPERLINK "" 14] The reaction was probably caused by sertraline.An infant was being breastfed (extent not stated) by a mother who began taking sertraline 50 mg daily and methylphenidate after 5 weeks postpartum. Dosage was started at 10 mg daily with an immediate-release product and gradually increased to 72 mg daily of an extended-release product. At 14 weeks of age, the infant was developing normally with no feeding difficulties. Examinations at 6 months and 1 year of age found no developmental problems in the child.[ HYPERLINK "" 29]In a study of sertraline for postpartum depression, 11 women completed the full 7-week duration of the study out of 36 who were entered. Six mothers reported breastfeeding their infants (extent not stated) and 5 did not breastfeed their infants. The average sertraline dose at week 7 was 100 mg daily. No side effects were reported for any of the infants in the sertraline or placebo groups at this time.[ HYPERLINK "" 30]Authors of a metaanalysis on sertraline reported 25 infants who were breastfed by mothers taking sertraline. Ten of the infants were exclusively breastfed, two were 80% breastfed and the breastfeeding status of the others was not reported. No adverse reactions occurred.[ HYPERLINK "" 5]A cohort of 247 infants exposed to an antidepressant in utero during the third trimester of pregnancy were assessed for poor neonatal adaptation (PNA). Of the 247 infants, 154 developed PNA. Infants who were exclusively given formula had about 3 times the risk of developing PNA as those who were exclusively or partially breastfed. Sixty-eight of the infants were exposed to sertraline in utero.[ HYPERLINK "" 31]A retrospective study of 30 nursing mothers who had been seen at a psychiatric outpatient facility, followed for at least 8 weeks, and prescribed sertraline found that adverse effects were reported in 5 (13%) of their infants. One mother was taking 25 mg daily, 3 mothers were taking 50 mg daily and 1 was taking 100 mg daily. The most commonly reported adverse events in the infants were insomnia and restlessness; constant crying and poor feeding were less commonly reported. All of the adverse effects developed within the first 2 weeks after initiation of maternal treatment and disappeared within the 3 days after drug discontinuation. Adverse effects failed to disappear in one infant after reducing the maternal dosage from 50 mg daily to 25 mg daily. There was no difference in prevalence of adverse effects between these infants and those in the same study whose mothers were prescribed paroxetine.[ HYPERLINK "" 32]A 12-day-old exclusively breastfed male infant presented with severe weight loss and hypernatremic dehydration because of inadequate milk intake and a 30% weight loss since birth. The infant's mother was being treated for bipolar disorder with lamotrigine 250 mg orally once daily, aripiprazole 15 mg orally once daily, and sertraline 100 mg orally once daily. She was also taking levothyroxine 50 mcg once daily, a prenatal multivitamin, and folic acid. On initial evaluation in the emergency department, he was pale, with marbled skin, dry mucous membranes, decreased skin turgor, and bluish feet with prolonged capillary refill. The right foot eventually became darker with blackened toes and he developed gangrene of the right lower limb, which did not respond to medical therapy and required amputation of all five toes and surgical debridement of the metatarsals. Necrosis was attributed to arterial microthrombi caused by disseminated intravascular coagulation after severe dehydration. The authors considered the mother's medications as a possible cause of the dehydration and related problems.[ HYPERLINK "" 33]A mother who was exclusively breastfeeding a 2-month-old infant began taking sertraline 50 mg daily for depression. Six days later, restlessness and a dramatic decrease in the duration of sleep in the baby was reported. Sertraline was discontinued and the symptoms completely resolved within 3 days. No abnormalities were seen on physical examination or laboratory tests. The infant subsequently developed severe constipation with maternal paroxetine use, but tolerated maternal citalopram use.[ HYPERLINK "" 34]A mother who was 3 months postpartum was treated for depression with sertraline 50 mg in the morning and olanzapine 1.25 mg at night at night for sleep. After 2 weeks, the sertraline dosage was increased to 25 mg in the morning and 50 mg at night. Five days after the dosage increase, her breastfed infant began having diarrhea about 15 minutes after each feeding. She continued the medication and provided oral rehydration solution to the infant. The diarrhea resolved after 2 weeks. The diarrhea was probably caused by sertraline in breastmilk.[ HYPERLINK "" 35]Nine women treated with sertraline 25 to 75 mg daily (7 were taking 50 mg daily) during the third trimester of pregnancy and during breastfeeding. Pediatric evaluations including neurologic assessments and brain ultrasound were conducted during the first 24 hours postpartum. Further follow-up was conducted at 6 or more months of age. Infant clinical status was comparable to unexposed infants from the same pediatric department.[ HYPERLINK "" 17]A case-control study in Israel compared 280 infants of nursing mothers taking long-term psychotropic drugs to the infants of 152 women taking antibiotics. Infant sleepiness at 3 days of age was reported by 1 mother taking sertraline during pregnancy and breastfeeding and by none taking antibiotics. The sleepiness resolved within 24 hours with no developmental effect.[ HYPERLINK "" 36]Effects on Lactation and BreastmilkSertraline has caused galactorrhea in nonpregnant, nonnursing patients.[37-41] However, in a study of cases of hyperprolactinemia and its symptoms (e.g., gynecomastia) reported to a French pharmacovigilance center, sertraline was not found to have an increased risk of causing hyperprolactinemia compared to other drugs.[42] The prolactin level in a mother with established lactation may not affect her ability to breastfeed.A midwife observed 6 patients who reported a decrease in milk supply after starting sertraline (dosages not reported). One of the mothers had been taking sertraline since the 6th month of pregnancy. She reported an increase in milk supply when she stopped sertraline for one week at 4 months postpartum. When she restarted sertraline, her milk supply reportedly decreased. In all of the women, the milk supply increased in 2 to 3 days after increasing fluid and the frequency of nursing.[ HYPERLINK "" 43]In a small prospective study, 8 primiparous women who were taking a serotonin reuptake inhibitor (SRI; 3 taking fluoxetine and 1 each taking citalopram, duloxetine, escitalopram, paroxetine or sertraline) were compared to 423 mothers who were not taking an SRI. Mothers taking an SRI had an onset of milk secretory activation (lactogenesis II) that was delayed by an average of 16.7 hours compared to controls (85.8 hours postpartum in the SRI-treated mothers and 69.1 h in the untreated mothers), which doubled the risk of delayed feeding behavior in the untreated group. However, the delay in lactogenesis II may not be clinically important, since there was no statistically significant difference between the groups in the percentage of mothers experiencing feeding difficulties after day 4 postpartum.[ HYPERLINK "" 44]A case control study compared the rate of predominant breastfeeding at 2 weeks postpartum in mothers who took an SSRI antidepressant throughout pregnancy and at delivery (n = 167) or an SSRI during pregnancy only (n = 117) to a control group of mothers who took no antidepressants (n = 182). Among the two groups who had taken an SSRI, 33 took citalopram, 18 took escitalopram, 63 took fluoxetine, 2 took fluvoxamine, 78 took paroxetine, and 87 took sertraline. Among the women who took an SSRI, the breastfeeding rate at 2 weeks postpartum was 27% to 33% lower than mother who did not take antidepressants, with no statistical difference in breastfeeding rates between the SSRI-exposed groups.[ HYPERLINK "" 45]An observational study looked at outcomes of 2859 women who took an antidepressant during the 2 years prior to pregnancy. Compared to women who did not take an antidepressant during pregnancy, mothers who took an antidepressant during all 3 trimesters of pregnancy were 37% less likely to be breastfeeding upon hospital discharge. Mothers who took an antidepressant only during the third trimester were 75% less likely to be breastfeeding at discharge. Those who took an antidepressant only during the first and second trimesters did not have a reduced likelihood of breastfeeding at discharge.[ HYPERLINK "" 46] The antidepressants used by the mothers were not specified.A retrospective cohort study of hospital electronic medical records from 2001 to 2008 compared women who had been dispensed an antidepressant during late gestation (n = 575; sertraline n = 200) to those who had a psychiatric illness but did not receive an antidepressant (n = 1552) and mothers who did not have a psychiatric diagnosis (n = 30,535). Women who received an antidepressant were 37% less likely to be breastfeeding at discharge than women without a psychiatric diagnosis, but no less likely to be breastfeeding than untreated mothers with a psychiatric diagnosis.[ HYPERLINK "" 47]Alternate Drugs to ConsiderNortriptyline, Paroxetine_____________________________Maternal depression is known to have an adverse effect on parenting and infant development.14 Tricyclic antidepressants have been shown to have little to no effect on the breastfeeding infant, although the AAP finds most tricyclic agents to be of possible concern.3, HYPERLINK "" \l "afp20010701p119-b7" 7 Taking a single daily dose at bedtime will limit the infant's exposure to the medication. The selective serotonin reuptake inhibitors (SSRIs) are generally the first choice of treatment for depression. Sertraline (Zoloft) is likely to be the safest choice among them because it has been studied extensively and because drug levels found in nursing infants are usually minimal.7, HYPERLINK "" \l "afp20010701p119-b12" 12Fluoxetine (Prozac) use during pregnancy has been well-studied, and many new mothers are already taking it at delivery. Its use during breast-feeding is controversial, however. Fluoxetine's long half-life and potential for accumulation in breast milk has prompted some recommendations to avoid its use in women who are breast-feeding young infants.3 Colic and fussiness have been attributed to elevated serum concentrations of fluoxetine and its metabolite in nursing infants.4 Results from a recent study showed a decrease in the level of fluoxetine and its metabolite in the early weeks of life in nursing infants whose mothers were maintained on fluoxetine throughout pregnancy and breast-feeding. This decrease implies an absence of accumulation of fluoxetine during exposure from breast milk.15 No long-term studies of neurologic outcomes of children with breast milk exposure to SSRIs are available. These children should be observed closely.At this time, it seems prudent to choose an SSRI with the lowest plasma levels in infants, such as sertraline (Zoloft) or paroxetine (Paxil).7, HYPERLINK "" \l "afp20010701p119-b14" 14 Another option is to measure serum concentrations of the SSRI and major metabolites in the infant at two to six weeks postpartum to verify that the medication is not accumulating. If the mother has taken fluoxetine during pregnancy, an infant serum level of fluoxetine and norfluoxetine at about six weeks should reflect drug accumulation from the breast milk instead of continued presence of the prenatal medication.15Why do most drugs appear in the milk in only small amounts? Because what gets into the milk depends on the concentration of drug in the breastfeeding parent’s blood, and the concentration in the breastfeeding parent’s blood is often measured in micro- or even nano-grams per millilitre (millionths or billionths of a gram), whereas the parent?takes the drug in milligrams (thousandths of grams) or even grams. Furthermore, not all the drug in the breastfeeding parent’s blood can get into the milk. Only the drug that is not attached to protein in the blood can get into the milk. Many drugs are almost completely attached to protein in the breastfeeding parent’s blood. Thus, the baby is not getting amounts of drug similar to the breastfeeding parent’s intake, but almost always, much less on a weight basis. For example, in one study with the antidepressant paroxetine (Paxil), the mother got over 300 micrograms per kg per day (the usual dose being 20 to 50 mg per day), whereas the baby got about 1 microgram per kg per day.if the concern is for the baby’s being?exposed to a drug, say an antidepressant, then the baby is getting exposed to much more drug at a much more sensitive time during pregnancy than during breastfeeding.? Recent studies about withdrawal symptoms in newborn babies exposed to SSRI type antidepressants (Paxil, for example) during the pregnancy somehow managed to imply that?breastfeeding should not be allowed because of the tiny amounts of drug in the milk as if this type of problem requires a mother not to breastfeed. In fact, you cannot prevent these withdrawal symptoms in the baby by breastfeeding, because the baby gets so little in the milk. In fact at least one study suggests that breastfeeding decreases the withdrawal symptoms in the baby, though I suspect it’s more the skin contact with the breastfeeding parent that decreases the symptoms, not the tiny amounts of drug in the milk.?Lorazepam, Midazolam, OxazepamOther medication: DoxycyclineDrug Levels and EffectsSummary of Use during LactationA number of reviews have stated that tetracyclines are contraindicated during breastfeeding because of possible staining of infants’ dental enamel or bone deposition of tetracyclines. However, a close examination of available literature indicates that there is not likely to be harm in short-term use of doxycycline during lactation because milk levels are low and absorption by the infant is inhibited by the calcium in breastmilk. Doxycycline use in children <8 years is now considered acceptable in courses up to 21 days. As a theoretical precaution, avoid prolonged (>21 days) or repeat courses during nursing. Monitor the infant for rash and for possible effects on the gastrointestinal flora, such as diarrhea or candidiasis (thrush, diaper rash).Drug LevelsMaternal Levels. Fifteen mothers nursing infants between 15 and 30 days old were given doxycycline 200 mg orally followed in 12 hours by another dose of 100 mg. Milk doxycycline levels were measured using a biologic assay 3 and 24 hours after the second dose. Milk doxycycline levels averaged 0.77 mg/L (range 0.4 to 1.4 mg/L) 3 hours after the dose and 0.38 mg/L (range 0.12 to 0.85 mg/L) 24 hours after the dose.[ HYPERLINK "" 1]A dose of 100 mg daily of doxycycline was given orally to 10 mothers. On the second day of treatment, milk doxycycline averaged 0.82 mg/L (range 0.37 to 1.24 mg/L) 3 hours after the dose, and 0.46 mg/L (range 0.3 to 0.91 mg/L) 24 hours after the dose.[2] Using the average of the peak and trough milk levels in this study, the estimated average intake of an exclusively breastfed infant would be about 6% of the maternal weight-adjusted dosage.After a single oral dose of 100 mg in 3 women and 200 mg in 3 women, peak milk levels occurred between 2 and 4 hours after the dose. Average peak milk concentrations were 0.96 mg/L after 100 mg and 1.8 mg/L after 200 mg. Milk levels accumulated to about 3.6 mg/L with doses of 100 mg twice daily for 5 days.[3]Another study found peak milk levels to occur 5 to 7 hours after oral doses of 100 or 200 mg in 13 women in the immediate postpartum period. Peak levels were 0.6 mg/L with the 100 mg dose in 3 women, and averaged 1.1 mg/L in 11 women who received 200 mg.[ HYPERLINK "" 4]After single 200 mg dose of doxycycline to 2 women, average milk levels were 0.8 mg/L 2 hours after the dose, 0.7 mg/L 4 hours after the dose, and 0.4 mg/L 6 hours after the dose.[5]Infant Levels. Relevant published information was not found as of the revision date.Effects in Breastfed InfantsRelevant published information was not found as of the revision date.Effects on Lactation and BreastmilkRelevant published information was not found as of the revision date.Alternate Drugs to ConsiderTetracycline ................
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