Medications and Mothers` Milk

Christine M. Betzold MSN NP IBCLC
UCI Assistant Clinical Professor
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Risks vs. Benefits
Resources: AAP and Hale
Pharmacodynamics
Infant and Maternal Risks
Breastfeeding Management
Key Points
Questions?
1Risk(s)
of the medication and 2Feeding Formula to the infant
vs
3Benefit(s)
of the medication and of 4Breastfeeding for the Mother
First: How do we determine the risk of the medication?
Avoid Using
1. Manufacturing Data!
Recommended
1.
NIH site:
http://toxnet.nlm.nih.gov/cgibin/sis/htmlgen?LACT
2. PDR!
2.
The AAP 2013 statement
3. Most Pharmacists!
3.
Medications in Mothers’
Milk (Hale)
4.
Infant Risk App (Iphone or
Android)
(Sorry)
AAP Medication Ratings
1. Maternal Medication usually Compatible with Breastfeeding.
2. Drugs for Which the Effect on Nursing Infants Is Unknown but May
Be of Concern.
3. Drugs That Have Been Associated With Significant Effects on Some
Nursing Infants and Should Be Given to Nursing Mothers With
Caution.
4. Radioactive Compounds That Require Temporary Cessation of
Breastfeeding.
5. Drugs of Abuse for Which Adverse Effects on the Infant During
Breastfeeding Have Been Reported.
6. Cytotoxic Drugs That May Interfere With Cellular Metabolism of the
Nursing Infant.
Hale’s Medications in Mothers’ Milk
1.
Infant Risk App (Iphone or Android)
www.infantrisk.com or Center: 806-352-2519
2.
Book ordering information:
www.ibreastfeeding.com or 1-800-378-1317
Lactation Risk Categories:
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L1
L2
L3
L4
L5
Safest
Safer
Moderately/Probably Safe
Possibly Hazardous
Contraindicated
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Maternal Milk Levels
Lists Known Adult/Pediatric Side Effects
Nursing Infant Blood Levels
Case Reports of Nursing Infant(s) Side Effects or
Injury
• May Estimate the Relative Infant Dose [RID] (most
drugs is <1% and if the RID is less than 10%, it is
likely to be safe to use)
Pharmacodynamics
INCREASES MILK
CONCENTRATION
MILK
SEQUESTRATION
EFEECTS ON
PLASMA LEVELS
OTHER
CONSIDERATIONS
INFANT
CONSIDERATIONS
ORAL
BIOAVAILABILITY
Lipid Solubility
Milk/Plasma
Ratio >1
Half-Life: Short
vs Long Acting
Maternal
Treatment Length
Age
Gut Destruction i.e. Is
it Denatured?
Low Molecular
Weight
pH at Which
Equally Ionic
(>7.2)
Volume
Distribution (High
tends to Lower)
Effects on Milk
Supply
Health Conditions
and Gut
Permeability
Route and Timing of
Administration
Low Protein
Binding
Time of Peak
Plasma Level
Active Metabolites
Concurrent
Medications
Sequestration in the
Liver
Passes the
Blood—Brain
Barrier
Maternal Dose
Approved for
Pediatric Usage
Any Allergies?
Nursing Frequency or
Exclusivity
Availability of a
“Preferred” or
“Safer”
Medication
Pediatric Half-Life
Relative Infant Dose
<10% Usually Safe
High Maternal
Plasma Levels
National Breastfeeding Campaign Ads—Highlighted Risks
Strong evidence




Bacteremia
Bacterial meningitis
UTI
Late-onset sepsis
Some Evidence
 Hodgkin Disease (3 studies)
 Hypercholesterolemia (1 study)
 Provides analgesia (2 Studies)
• Higher IQ
• More White Matter (Deonia S, Dean D, Piryatinskya I, et al. Breastfeeding and early
white matter development: A cross-sectional study. NeuroImage, 2013 (82), 77–86.)
• Premature Infants
VOHR Study
•For every 2 tsp/kg (i.e ~1 tsp/lb):
•Psychomotor Developmental Index > 0.56 points
•Total Behavior Percentile score > 0.99 points
•Bayley Mental Developmental Index > 0.59 points
•Risk of Hospitalization < 5%
(Vohr-ELBW Premature Infants www.pediatrics.org/cgi/doi/10.1542/peds.2006-3227)
Full Term
Exclusively
Breastfed IgA
Weight
Calculating Dose
Weekly
Dose/kg
Daily
Dose/kg
Comments
2.5-5.0 kg
Colostrum: 1 gm/day
N/A
700-1400mg
200-400mg
Dosage/kg will
drop as infant
grows
1500-6000 mg
215-860mg
2.5-5.0 kg
Antibody
Deficiency
Replacement IVIG
Milk 4-52 wks: >500mg/day
>3500mg/wk
200-400mg/kg
3 times/week
100-200mg
Sources:
1.
Arch Dis Child 1998;78:235-239 doi:10.1136/adc.78.3.235 (http://adc.bmj.com/content/78/3/235.full)
2.
www.ncbi.nlm.nih.gov/pmc/articles/PMC1809480/
Dosage/kg will
increase as
child grows
Environmental—Less
Pollution
Business—Recoup
$2-3 dollars for every
$1 spent on Lactation
Support
Bartick Study
• if 90% Exclusively Bf for
6 months:
• 13 billion
• $3,430.00/infant
• At 80%:
• $10.5 Billion
www.pediatrics.org/cgi/doi/10.1542/peds.
2009-1616
Study area
Berlin, Germany
Date
Mortality Rate (per 1000)
Breastfed Artificially Fed
1895-1896
57
376
Difference
319
Eight U.S. cities[†]
1911-1916
76
255
179
Chicago, Ill.
1924-1929
2
84
82
Liverpool, England
1936-1942
10
57
47
Great Britain
1946-1947
9
18
9
From Knodel J: Breastfeeding and population growth. Science 198:1111, 1977.
Most of these rates do not include deaths in the first few days or weeks of life; mortality rate is therefore underestimated and
survival rate overestimated. Only the rates for the eight U.S. cities in 1911-1916 represent mortality rate from birth; deaths that
occurred before any feeding are proportionately allocated to the two feeding categories. The rates for Berlin, Bremen, Hanover,
Cologne, and the eight U.S. cities were derived by applying life table techniques to mortality rates given by single months of
age.
†
‡
observation.
Comparison of breastfed infants with infants artificially fed from birth.
Comparison of breastfed infants with all infants artificially fed in the period of
Mortality risk of bottle feeding
Country, yr
Age
RR
Attributable risk
Comment
England, 1986
1m-1yr
US, 1989
0-1yr
Rwanda, 1981
0-2 yr
2.0
135/1000
Hospital Case
Fatality
Egypt, 1981
~0-3 yr
2.0-3.0
130-290/1000
Cumulative mortality
to next sibling
<5.1/1000
General Prevention
Program
4/1000
Mathematical Model
Source: Cunningham A et al. Breastfeeding and health in the 1980’s: A global epidemiologic review.
J Pediatrics, 1991; 118 (5) 659-665.
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N= 24,566 all single live-births from 1988 &1995
Infants that are breastfed are 80% less likely to die before age 1
than are never breastfed infants.
Black
Infant
Age
OR’s
Deaths
Prevented
Rate/100,
000
Ever
Breastfed
1-11
months
0.188
580
15
The Decision to BF in the US: Does Race
Matter?
Pediatrics Vol. 108 No. 210/01, pp.291-296
and personal communication R. Forste 1/22/02
Slide by Christine Betzold NP MSN IBCLC
Study
Participants
N=
Breastfeeding
Deaths
Prevented
Other
Chen, 2004
1988 NMIHS data
Control
7740
Ever and Duration
~720
0.79 lower risk
Longer BF
associated with
lower risk
90% Exclusively for
6m
911 (nearly all
infants)
At 80%:
741
Cases
1204
Bartick,
2009
Total Births in
2005
4.4
million
births
Sources: Pediatrics. 2004;113(5). Available at: www.pediatrics.org/cgi/content/full/113/5/e435 and
www.pediatrics.org/cgi/doi/10.1542/peds.2009-1616
Infant deaths and infant mortality rates for the 10 leading causes of infant death: United
States, preliminary 2010
Data are based on a continuous file of records received from the states. Rates are per 100,000 live births.
Rank
Cause of death
Number
Rate
1
Congenital malformations, deformations and chromosomal abnormalities
5,077
126.9
2
Disorders related to short gestation and LBW, not elsewhere classified
4,130
103.2
3
SIDS
1,890
47.2
4
Newborn affected by maternal complications of pregnancy
1,555
38.9
5
Accidents (unintentional injuries)
1,043
26.1
6
Newborn affected by complications of placenta, cord and membranes
1,030
25.7
7
Bacterial sepsis of newborn
569
14.2
8
Diseases of the circulatory system
499
12.5
9
RDS of newborn
496
12.4
10
NEC of newborn
470
11.7
...
All other causes (Residual)
http://www.cdc.gov/nchs/data/nvsr/nvsr60/nvsr60_04.pdf
7,789
Infant deaths and infant mortality rates for the 10 leading causes of infant death: United
States, preliminary 2010
Data are based on a continuous file of records received from the states. Rates are per 100,000 live births.
Rank
Cause of death
Number
Rate
1
Congenital malformations, deformations and chromosomal abnormalities
5,077
126.9
2
Disorders related to short gestation and LBW, not elsewhere classified
4,130
103.2
3
SIDS
1,890
47.2
4
Newborn affected by maternal complications of pregnancy
1,555
38.9
5
Accidents (unintentional injuries)
1,043
26.1
6
Newborn affected by complications of placenta, cord and membranes
1,030
25.7
7
7
Bacterial
of newborn
Formula sepsis
Feeding*
(2004 and 2009)
569
721-900+
14.2
20?
8
8
Diseases sepsis
of the circulatory
Bacterial
of newbornsystem
499
569
12.5
14.2
9
RDS of newborn
Diseases
of the circulatory system
496
499
12.4
12.5
10
NEC of newborn
RDS
470
496
11.7
12.4
...
11
All other
causes (Residual)
NEC
of newborn
7,789
470
11.7
http://www.cdc.gov/nchs/data/nvsr/nvsr60/nvsr60_04.pdf
Maternal Benefits
– Decreased Risk of Rheumatoid Arthritis
– Less Blood Loss and Faster Involution
– Child Spacing and Contraception (LAM)=Fewer
Premature Infants
– Lower Risk of Infant/Child Neglect or Abuse
– PPD
– Weight Loss (?)
AAP 2012 Policy Statement: www.pediatrics.org/cgi/doi/10.1542/peds.2011-3552
(Obstet Gynecol 2013;122:111–9)
N=U.S. cohort of 1.88 million women 15-70 yrs
WHAT: The direct and indirect costs expressed in 2011 dollars If 90% breastfeed for > 1 year (the
current rate is 23%)
1.
2.
3.
4.
Premature Death: $17.4 billion
Direct: $733.7 million
Indirect Morbidity: $126.1 million
Maternal Death <70 yrs=4,396 additional premature deaths, 95% CI –810–7,918 (p=NS)
Questions/Comments?
Colds and Flu
Unsafe
Comments
Phenergan w/ Codeine
Ok alone—too sedating together
I-desoxyephedrine
Vicks Vapor Inhaler
Ephedrine
Rynatuss/Primatine/Pretz-D
Clemastine
Tavist Allergy
propylhexedrine
Bezedrex
Zinc/Zincum
High Dose: Zicam Liquid Nasal
gel/Swabs/Nasal Ease
Caution
Comment
Pseudoephedrine
May lower milk
Supply/Observe for
Excitation
Epinephrine HCL 1
(Adrenaline Chloride)
Observe for Excitation
Zinc/Zincum
Check Dose/Low dose OK
Levmetamfetamine
(Nuprin Cold Relief
Inhaler)
Observe for Excitation
Safe/Probably
Safe
Comment
Dextromethorphan
Codeine
Hyrdocodone
Observe for sedation
Guaifenesin
Carbetapentane
Observe for sedation
(Carbetapentane)
Brompheniramine
Diphenhyrdamine
Chlorpheniramine
Carbinoxamine
Fexofenadine
Doxylamine
Cetirizine
Loratadine
Pyrilamine
Observe for sedation
Phenylephrine
Oxymetazoline (nasal)
Tetrahydrozoline HCL
Naphazoline HCL (inhaler)
Xylometazoline HCL
Observe for Excitation
Antipsychotics/Depression
L1-3
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Use w/ Caution
Sertraline (Zoloft)*
• (Fluoxetine) Prozac
Paroxetine (Paxil)
Long Half-life (Colic?)
Escitalopram (Lexapro)
• Bupropion (Wellbutrin)
Amitriptyline (Elavil)
– LOW MILK SUPPLY
Trazadone (Desyrel)
• Lithium L3-4?
Venlafaxine (Effexor)
– Baby must be monitored
Quetiapine fumarate (Seroquel) – Labs
– Development
Risperidone (Risperdal)
– Lethargy/hypotonia
Lorazepam (Ativan*)
– Dehydration
Aloprazolam (Xanax)-short term
or intermittently
*Preferred Medication
Rheumatologic and Immunosuppressant
Agents
Medication
Lactation
Risk
Ranking*
Other information
Aspirin
L3
NSAIDS
Varies
Acetominophen
L1
Steriods
L2
Antimalarials
L2
Anticoagulants
L1 and L2
Warfarin: Watch for bleeding and/or supplement infant with Vit K
Heparin
Anti-TNF
Fusion Proteins
L3
Abatacept and Etanercept
Large Molecular Weight—don’t use concurrently with other anti-TNF products
Interferon Beta
1A & 1B
L2
(Avonex, Betaseron) Very large molecular size;data shows minimal amounts were
present in milk. Interferons are also given to children for different conditions and are
generally nontoxic.
Monoclonal
antibodies
L2-3
Benlysta, Adalimumab, and Rituximab (L3)
Infliximab (L2)
Because of Reyes Syndrome aspirin therapy should be interrupted if the infant
becomes ill.
Ibuprofen is the preferred NSAID (L1) Clinoril (L3) Naproxen (L3 for short-term
use)
N/A
Prednisone or methylprednisolone: Watch infant growth closely especially with
long-term high dose therapy. Poor growth has not been reported to date. High Dose
such as 1000 mg, pump and discard for 24 hours.
Hydroxychloroquine; Chloroquine
Medication
Lactation
Risk
Ranking*
Other information
Copaxone
(glatiramer)
L3
No data available on the transfer into breast milk, but the
drug has a large molecular size.
Infant Reports of Scratching after dose suggest pumping
and discarding 2 hrs post dose
Tysabri
(natalizumab)
L3
Large molecular size also, but we do not have data thus far.
Observe for rash, flushing, and low blood pressure
although not likely to occur.
Sulfasalazine
L3
One idiosyncratic allergic response use with cautionobserve for diarrhea
Cyclosporine
L3
Milk Levels usually very low and infant blood levels usually
subclinical and undetectable. 1 case infant had therapeutic
blood levels so check infant levels
Anakinra
L3
Large Molecular Weight—Watch infant for GI infections
Tacrolimus
(Prograf)
Azathioprine
L2
L3
Topical or Oral. Poorly absorbed topically.
Consider monitoring infants CBC w/diff and Liver Enzymes
Use <3 weeks, Interrupt Breastfeeding or
Recommend Weaning
Medication
Lactation Risk
Ranking*
Other information
Methotrexate
Cyclophosphamide
L4-5
Methotrexate: If the mother takes a single dose <50 mg then
she should pump and dump for 24 hours. If the dose is > 50
mg then she should pump for 4 days. Wean if repeated doses
3 or more times weekly needed.
Cyclophosphamide: if given short-term mom should pump and
dump at least 72 hours.
Naproxen
L3-4
Naproxen (L3 for short-term; L4 for chronic Use)
Gold Compounds
(Ridaura/Solganal)
L5
Oral absorption is quite low but prolonged exposure may lead
to accumulation and this may be risky
Minocycline
L3-4
L3 <3 wks
Leflunomide (Arava)
L5
No data T1/2 is 15-18 hrs
Penicillamine
L4
Chelating agent T1/2 is 1.7-3.2 hrs
Mycophenolate Mofetil
(Cellcept)
L4
No data
L4 >3wks
Don’t Use
1.
Dopamine Agonists e.g.



2.
3.
Drugs of Abuse
Some Herbals e.g.



4.
Blue Cohosh
Borage
Kava Kava
Retinoids e.g.



5.
Levodopa
Bromocriptine
Cabergoline
Acitretin
Isotretinoin
Etretinate-long half-life
Appetite Suppressants e.g.


Diethylpropion
Phentermine
6. Miscellaneous Drugs (High RID, Lower
Milk Supply and/or w/ Infant Side Effects)
Amiodarone (RID 4-6%)
Chloramphenicol (RID 2%)
Danazol (LMS, Infant SE)
Dicyclomine (LMS, Infant Apnea)
Diethylstilbestrol (LMS, Infant SE)
Disulfiram (Infant SE if Mother ingest ETOH)
Doxepin (High Infant levels of Active Metabolite)
Ergotamine (LMS, Infant SE)
 Phenindione (RID 18%)
 Zonisamide (RID High and S.E.)
Other Drugs That Should Not be Used or
Require Interruption
•Antineoplasic
•Radioactive Iodides
— Check T ½
•Fluorouracil-topical might be OK?
•NOT RADIOPAQUE!
•Mitoxantrone-long half-life
•Oxaliplatin-long half-life
— Check listings for T ½ at:
pbadupws.nrc.gov/docs/ML0833/ML083300045.pdf
•Paclitaxel-long half-life
•Tamoxifen-long half-life
In general Breastfeeding Interuption should last @ 5 half-lives. Milk exposed to
Radioactive substances can be saved, scanned for radioactivity and fed once
dissipated.
Mother’s Condition
Medication
1. Hyperthyroid
2. Renal Failure
1. Methimazole
3.
4.
5.
6.
7.
3. Prozac
Depression
Asthma
Severe Poison Ivy
Hypertension
Thyroid Nodule
2. Tacrolimus (Prograff) and
Azathioprine (Imuran)
4. Proventil
5. Prednisone
6. Atenolol
7.
99mTcO
4
1-2mCi
Interrupted Breastfeeding
• Usually 5—½ lives
• Supply a high-quality double-electric pump
– Medela Pump-n-Style
– Ameda Purely Yours
– Or Hospital Grade Rental
• Must pump every 2-3 hours to maintain
supply (one 4-6) break at night is OK
• Pump and Dump or Pump and Save
• If fully nursing:
1. Drop one feeding every couple of days--start with the one
she least enjoys or is least able to do.
2. Encourage weaning over no less than 3 weeks in order to
avoid maternal complications such as engorgement,
mastitis or plugged ducts.
3. If uncomfortable nurse or express just enough to relieve
discomfort.
4. Faster weaning leads to Milk Retention
5. Milk Retention: increases risk of mastitis/abscess
1. Increase stimulation via pumping and/or feeding. (For a
full milk supply mom needs to stimulate a minimum of every 3 hours or 8
times per day—one 4-6 hour break at hs is allowable)
2. Refer to CLC if mom wants to use a supplementer
3. Start Fenugreek and/or Metoclopramide (Reglan)
4. Metoclopramide (Reglan) Dosage:
– 10mg one p.o. tid (can taper up over 3 days, maintain until full
milk supply or supply plateaus and taper down over 3 weeks)
• Blessed Thistle
• Fennel
• Goat’s Rue
(May promote breast
growth if used long
enough)
• Brewers Yeast
• Oatmeal
Final Points
1. The risks of formula-feeding almost always outweigh the risk
exposure via breastfeeding
2. Don’t forget to evaluate the infant for risks like concurrent meds or
allergy to medication.
3. Choose drugs (when possible):
1. that have published data and use legitimate resources.
2. with short half-lives, high protein binding, low oral bioavailability, or high
molecular weight
4. Educate the mother about the potential side effects in the infant and/or
to her milk supply.
5. If Temporary interruption of breastfeeding recommended make sure
mom has a double electric pump knows to pump 8x per day.