Christine M. Betzold MSN NP IBCLC UCI Assistant Clinical Professor

• 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?

1. Manufacturing Data!

2. PDR!

3. Most Pharmacists! (Sorry)

Avoid Using Recommended

1. NIH site: http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT

2. The AAP 2013 statement

3. Medications in Mothers’ Milk (Hale)

4. Infant Risk App (Iphone or Android)

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.

Lactation Risk Categories:

• L1 Safest • L2 Safer • L3 Moderately/Probably Safe • L4 Possibly Hazardous • L5 Contraindicated

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

• 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)

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

High Maternal Plasma Levels

Availability of a “Preferred” or “Safer” Medication

Pediatric Half-Life

Relative Infant Dose <10% Usually Safe

Pharmacodynamics

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)

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/

Weight Calculating Dose Weekly Dose/kg

Daily Dose/kg

Comments

Full Term Exclusively Breastfed IgA

2.5-5.0 kg

Colostrum: 1 gm/day Milk 4-52 wks: >500mg/day >3500mg/wk

N/A 700-1400mg

200-400mg 100-200mg

Dosage/kg will drop as infant grows

Antibody Deficiency Replacement IVIG

2.5-5.0 kg

200-400mg/kg 3 times/week

1500-6000 mg 215-860mg Dosage/kg will increase as child grows

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

Environmental—Less Pollution Business—Recoup $2-3 dollars for every $1 spent on Lactation Support

Mortality Rate (per 1000) Study area Date Breastfed Artificially Fed Difference Berlin, Germany 1895-1896 57 376 319 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. † Comparison of breastfed infants with infants artificially fed from birth. ‡ Comparison of breastfed infants with all infants artificially fed in the period of observation.

Mortality risk of bottle feeding Country, yr Age RR Attributable risk Comment

England, 1986 1m-1yr <5.1/1000 General Prevention Program

US, 1989 0-1yr 4/1000 Mathematical Model

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

Source: Cunningham A et al. Breastfeeding and health in the 1980’s: A global epidemiologic review. J Pediatrics, 1991; 118 (5) 659-665.

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

• 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.

Slide by Christine Betzold NP MSN IBCLC

Black Infant

Age OR’s Deaths Prevented

Rate/100,000

Ever Breastfed

1-11 months

0.188 580 15

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

Study Participants N= Breastfeeding Deaths Prevented

Other

Chen, 2004 1988 NMIHS data Control 7740

Cases 1204

Ever and Duration ~720 0.79 lower risk

Longer BF associated with lower risk

Bartick, 2009

Total Births in 2005

4.4 million births

90% Exclusively for 6m

911 (nearly all infants)

At 80%: 741

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) 7,789

http://www.cdc.gov/nchs/data/nvsr/nvsr60/nvsr60_04.pdf

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) 7,789

7 Formula Feeding* (2004 and 2009) 721-900+ 20?

8 Bacterial sepsis of newborn 569 14.2

9 Diseases of the circulatory system 499 12.5

10 RDS of newborn 496 12.4

11 NEC of newborn 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)

WHAT: The direct and indirect costs expressed in 2011 dollars If 90% breastfeed for > 1 year (the current rate is 23%)

1. Premature Death: $17.4 billion 2. Direct: $733.7 million 3. Indirect Morbidity: $126.1 million 4. Maternal Death <70 yrs=4,396 additional premature deaths, 95% CI –810–7,918 (p=NS)

N=U.S. cohort of 1.88 million women 15-70 yrs

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

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

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

Antipsychotics/Depression L1-3

• Sertraline (Zoloft)* • Paroxetine (Paxil) • Escitalopram (Lexapro) • Amitriptyline (Elavil) • Trazadone (Desyrel) • Venlafaxine (Effexor) • Quetiapine fumarate (Seroquel) • Risperidone (Risperdal) • Lorazepam (Ativan*) • Aloprazolam (Xanax)-short term

or intermittently

Use w/ Caution

• (Fluoxetine) Prozac Long Half-life (Colic?)

• Bupropion (Wellbutrin) – LOW MILK SUPPLY

• Lithium L3-4? – Baby must be monitored – Labs – Development – Lethargy/hypotonia – Dehydration

*Preferred Medication

Rheumatologic and Immunosuppressant Agents

Medication Lactation Risk Ranking*

Other information

Aspirin L3 Because of Reyes Syndrome aspirin therapy should be interrupted if the infant becomes ill.

NSAIDS Varies Ibuprofen is the preferred NSAID (L1) Clinoril (L3) Naproxen (L3 for short-term use)

Acetominophen L1 N/A

Steriods L2 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.

Antimalarials L2 Hydroxychloroquine; Chloroquine 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)

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 caution-observe 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)

L2 Topical or Oral. Poorly absorbed topically.

Azathioprine L3 Consider monitoring infants CBC w/diff and Liver Enzymes

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 L4 >3wks

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

Use <3 weeks, Interrupt Breastfeeding or Recommend Weaning

Don’t Use

1. Dopamine Agonists e.g. Levodopa Bromocriptine Cabergoline

2. Drugs of Abuse 3. Some Herbals e.g.

Blue Cohosh Borage Kava Kava

4. Retinoids e.g. Acitretin Isotretinoin Etretinate-long half-life

5. 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

In general Breastfeeding Interuption should last @ 5 half-lives. Milk exposed to Radioactive substances can be saved, scanned for radioactivity and fed once

dissipated.

•Radioactive Iodides

•NOT RADIOPAQUE!

— Check listings for T ½ at: pbadupws.nrc.gov/docs/ML0833/ML083300045.pdf

•Antineoplasic — Check T ½

•Fluorouracil-topical might be OK?

•Mitoxantrone-long half-life

•Oxaliplatin-long half-life

•Paclitaxel-long half-life

•Tamoxifen-long half-life

Mother’s Condition 1. Hyperthyroid 2. Renal Failure

3. Depression 4. Asthma 5. Severe Poison Ivy 6. Hypertension 7. Thyroid Nodule

Medication 1. Methimazole 2. Tacrolimus (Prograff) and

Azathioprine (Imuran) 3. Prozac 4. Proventil 5. Prednisone 6. Atenolol 7. 99mTcO4 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.