Medications and Breastfeeding: Pharmacists as Part of the Mother’s Breastfeeding Team

Frank J. Nice, RPh, DPA, CPHP301-840-0270

fjncat@hotmail.comwww.nicebreastfeeding.com

I have the following relevant financial relationship to disclose: Modest value relationship as author for Hale Publishing

Medications and Breastfeeding: Current Concepts• Only essential drugs should be taken by the nursing

mother. She should be knowledgeable of and be encouraged to report any adverse effects

• For newer drugs, sufficient information is often unavailable. If information is available, it requires careful interpretation and evaluation

• Recognizing the benefits of continuing to nurse, in most cases, drugs that have safe therapeutic levels can be given

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• The long-term effects of most drugs - on mothers as well as on their nurslings - often are not known

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• Use all available resources

Drug FactorsGeneral Guidelines1. Most drugs appear in breast milk to some degree

2. Levels of most drugs in breast milk do not usually exceed 1% to 2% of ingested maternal dosage

3. If the milk/plasma ratio of drug and active metabolites is less than 1:1, it is usually safe to breastfeed

4. RID: If infant dose is less than 10% of maternal dose (weight adjusted), it is usually safe to breastfeed

Drug FactorsPharmacokinetics1. Volume of Distribution

(1-20 L/Kg)

2. pH (breast milk more acidic)

3. Lipids

4. Protein-Bound Drugs (>85%)

5. Molecular Size (Daltons) (>200-400)

6. Active Transport

Maternal FactorsPharmacodynamics 1. Mammary epithelium may have drug -

metabolizing capacity

2. Milk volume is usually greatest in the early morning

3. Fat content of milk is usually highest in the late morning

4. Stage of breastfeeding is factor

Stages of Breastfeeding

•Newborns feed every 1-2 hours (Why?)•Colostrum (0-3 days)•Transitional Milk (4-7 days)•Mature Milk (7-10 days)•Alveolar Spaces (0-7 days)

Infant Factors (See Handout) Pharmacodynamics 1. Infant’s ability to absorb and metabolize

drugs2. Infant’s ability to detoxify and excrete drugs

through metabolic enzymes3. Miscellaneous factors

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No, it is not safe to breastfeed. You

should wean your baby.

Is Drug X OK to take while breastfeeding?

Oops; we needto ask somequestions here!

Lack of encouragement andinformed counseling from healthcare professionals (including pharmacists) on medication use duringbreastfeeding is one of the main obstacles to successful breastfeeding

Questions To Ask In Drug / Breastfeeding Situations (See Handout)

1. What is the name, strength, and dosage of the drug?

2. Do you still have the prescription? Or, have you already filled it and are taking the drug?

3. Why is the drug being prescribed?

4. Do you feel you need to take the drug?

5. What does your doctor say regarding breastfeeding outcome and taking the drug?

6. What is the drug?

Questions To Ask In Drug / Breastfeeding Situations (See Handout)

7. How old is your baby?

8. Was your baby full-term or premature?

9. What is your baby's weight?

10. Is your baby currently receiving any medication?

11. Do you know how to hand-express breast milk or do you have access to a breast pump?

12. Is this your first breastfed baby?

Stepwise Approach To Minimizing Infant Drug Exposure (See Handout)

1.   Withhold the drug

2.   Try nondrug therapy

3.   Delay therapy

4.   Choose drugs that pass poorly into breast milk

5. Choose more breastfeeding compatible

dosage forms

Stepwise Approach To Minimizing Infant Drug Exposure (See Handout)

6. Choose an alternative route of administration

7.    Avoid nursing at times of peak drug concentrations in milk8.    Administer drug immediately after

breastfeeding and / or before infant's longest sleep

9.    Temporarily withhold breastfeeding10. Discontinue breastfeeding (wean)

Mrs. Maine and Daughter Acadia After Birth

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CASE STUDY•Mrs. Maine, a breastfeeding woman, presents a

prescription to the pharmacist for an antibiotic to be filled. She is worried about taking this medication while breastfeeding and asks for the pharmacist’s recommendation. She wants to know if the antibiotic is safe to take while breastfeeding her baby, Acadia.

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CASE STUDY (continued)

•After the pharmacist asks the mother several questions about herself and her baby, the mother states that she will be back in two hours to pick up her filled prescription if you determine that the drug is usually safe to take while breastfeeding.

•What questions should the pharmacist have asked the mother?

Questions to Ask Mrs. Maine•Are you breastfeeding (Duh: in case patient did

not tell you she was breastfeeding)?•Mother’s DOB and Acadia’s DOB•Mother’s weight and Acadia’s weight•Any allergies (including drugs) for mother and

Acadia•Are mother and Acadia taking any other

medications, including OTCs, herbals, and vitamins?

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CASE STUDY (continued)

•From the mother, the pharmacist was able to obtain the following information:

•The mother weighs 110 pounds (50 Kg). The mother and baby have no drug allergies. Her baby is seven months old, taking no medications, and weighs 22 pounds (10 Kg). Breastfeeding is going very well.

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CASE STUDY (continued)

•The prescription is for: Xybotic, 1000 mg every twelve hours for five days (2000 mg per day)

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CASE STUDY (continued)

•Will the pharmacist be able to fill the prescription as written with enough assurance that when Mrs. Maine takes Xybotic, it should be safe for her to continue to breastfeed Acadia while taking the drug?

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CASE STUDY (continued)

•The pharmacist is unable to find any research or case study reports regarding Xybotic while breastfeeding. (Why?)

•What is the next step?

Next Step•The pharmacist runs a computer search on

Xybotic.•The pharmacist chooses to search Micromedex.

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CASE STUDY (continued)

•The pharmacist runs a Micromedex search on Xybotic and comes up with the following information:

•Xybotic is 90 percent bound to plasma protein, has a fairly low fat solubility, has a volume of distribution of 1400 L, has a molecular mass (size) of 300 Daltons, peaks in plasma in one hour, and has a half-life of four hours.

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CASE STUDY (continued)

•Protein: +•Fat Solubility: +•Daltons: +/-•Volume of Distribution: +•Peak: Avoid breastfeeding 0-2 hours after dose,

if possible•Half-Life: Should not accumulate in baby (Why?)

Relative Infant Dose (RID)• If RID is less than 10%, medication is “usually”

compatible with breastfeeding•Calculation:

Baby’s weight adjusted dose / Mother’s weight adjusted dose =

RID (expressed as %)

Relative Infant Dose (RID)• The pharmacist also is able to find a drug reference in

Micromedex that states when five mothers took Xybotic, an average of 0.01 mg of the drug appeared in 1 mL (10 mg/L) of breast milk {or 150 mL/Kg (baby)/day}

•Doing the calculations for the RID:• Baby’s weight adjusted dose: 1 mg/Kg/day (10 mg

drug dose daily from ingested milk / 10 Kg child’s weight)

•Mother’s weight adjusted dose: 40mg/Kg/day (2000 mg daily drug dose / 50 Kg mother’s weight)

• Baby/Mother Percentage (RID) (1/40) = 2.5%

Photo Courtesy of NIH

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CASE STUDY (continued)•What recommendation should the pharmacist

provide to Mrs. Maine as she is counseled?•What should the pharmacist do if the drug was not

compatible with breastfeeding?

Recommendation•OK to breastfeed while taking Xybotic•Observe for possible adverse effects in child

(diarrhea or possible allergic reaction)•Not necessary, but can avoid breastfeeding until

2 hours after taking drug

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What Else Could The Pharmacist Do?•Look for breastfeeding compatible alternative in

the same drug category (e.g., Hale and LactMed suggest alternatives) (see Handouts)

• If no alternative drug, go through the Stepwise Approach (see Handout)

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Prescription Drugs• Nonnarcotic Analgesics: Acetaminophen, ibuprofen, and

NSAIDs with short half-lives are the drugs of choice• Narcotic Analgesics: Codeine and similar narcotics (except

for patients who are rapid metabolizers) are the drugs of choice

• General and Epidural Anesthetics: These may decrease latching and maintenance of feeding

• Anti-Infectives: Most are compatible; monitor for allergic reactions

• Antihistamine/Decongestants: May decrease milk production (especially if breastfeeding after six months); maintain adequate fluid intake when used

Prescription Drugs•Bronchodilators: Inhalants are the most

compatible form to use•Corticosteroids: Usually compatible; inhalants are

the most compatible form to use•Antihypertensives: Each drug category has

compatible drugs•Diuretics: Usually compatible; maintain adequate

fluid intake when used•Cardiac Drugs: Each drug category has compatible

drugs

Prescription Drugs•Anticoagulants: Heparin and warfarin are compatible•Antidiabetics: Insulin and metformin are the drugs of

choice•Thyroid/Anti-Thyroid Drugs: Thyroid is compatible;

check individual anti-thyroid drugs for compatibility•Hormone Contraceptives: May decrease milk supply

and affect milk quality and milk components; wait 6 months before using

•Gastrointestinal Drugs: Antacids, H2 antagonists, and proton pump inhibitors are compatible: e.g., Pepcid, Zantac, Tagamet, Prilosec OTC

Prescription Drugs• Psychotherapeutic Drugs: Recommend that if antidepressant

taken during pregnancy, continue while breastfeeding. Also, may be started during breastfeeding. Benefit-risk analysis favorable and condoned by AAP and APA (See next slide for antidepressant drugs of choice)

• Benzodiazepines: Single, low dose, short half-life drugs compatible; oxazepam is drug of choice

• Antiepileptics: Most are compatible based on benefit-risk analysis. Combination drug treatment may cause poor sucking feeding.

• Radiopharmaceuticals: Can test milk samples and/or follow established guidelines for individual agents

• Miscellaneous: All vaccines, except smallpox (due to baby breastfeeding, physical nearness to vaccine site) are compatible

Antidepressant Drugs of Choice•1. Sertraline (Zoloft)•2. Escitalopram (Lexapro)•3. Paroxetine (Paxil)•4. Venlafaxine (Effexor)•5. Fluvoxamine (Luvox)•6. Citalopram (Celexa)•7. Fluoxetine (Prozac)

Adverse Effects(Overall Rate: 1%)•Psychotherapeutics (Antidepressants, Sedatives, Antipsychotics): 31%•Antimicrobials: 17%•Anticonvulsants: 16%•Analgesics (NSAIDs, Opioids): 12%•Hormonal Drugs: 5%• Iodides: 5%•Cardiovascular Drugs: 4%•GIT Drugs: 2%•Antihistamines: 2%•Chemotherapeutics: 2%

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Adverse Effects• Psychotherapeutics (Antidepressants, Sedatives, Antipsychotics): Drowsiness• Antimicrobials: Diarrhea• Anticonvulsants: Drowsiness, sedation, poor feeding• Analgesics (NSAIDs, Opioids): Drowsiness, sedation• Hormonal Drugs: Decreased milk supply, volume,

quantity• Iodides: Thyroid suppression• Cardiovascular Drugs: Weakness, hypotension,

bradycardia• GIT Drugs: GIT upset• Antihistamines: Irritability, drowsiness• Chemotherapeutics: Toxic effects of treatment

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Adverse Effects (References)Anderson PO, Pochop SL, Manoguerra AS: Adverse

drug reactions in breastfed infants: less than imagined. Clin Ped: 42 (4), 325-40: 2003

Ito S, Blajchman A, Stephenson M, et al: Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. Am J Obstet Gynecol: 168 (5), 1393-9: 1993

Codeine Rapid Metabolizers•13-day breastfed baby dies from morphine

overdose in breast milk in mother taking codeine•How did that ever happen?

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Codeine Rapid Metabolizers• A 13-day old breastfed infant died from morphine overdose

when the mother took codeine to treat episiotomy pain.• After the death, a genetic test showed the mother to be a

rapid metabolizers of codeine.• The chance of being a rapid metabolizers ranges from less

than 1 per 100 to 28 per 100 people.• Only a genetic test can tell if a person is affected, but there is

only limited information about using this test for codeine metabolism to morphine.

• In most cases, codeine is, and continues to be, appropriate treatment for pain while breastfeeding.

• It should be used at the lowest dose for the shortest period of time.

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Codeine Rapid Metabolizers (continued)• The mother in this case noted excess drowsiness in herself, so

the physician lowered the dose, but the drowsiness continued.• The mother continued to take the codeine for an extended time.• During this time, her baby also began to experience similar

signs because of the high level of morphine in the breast milk.• After 13 days, the baby experienced depression and died.• It seems apparent that the mother was not counseled properly

on the potential adverse effects of codeine (rapid metabolizers or not) on her breastfed child.

• A mother should never have a breastfed baby in respiratory depression before realizing the medication she is taking has led to the outcome.

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CONSIDERATIONS: OTC Medications• Analgesics• Cough, Cold, and Allergy

Preparations• Cough and Cold Lozenges and

Sprays• Nasal Preparations• Asthma Preparations• Antacids and Digestive Aids• Laxatives / Stool Softeners

• Anti-Diarrheal Preparations• Nausea and Vomiting / Motion

Sickness Preparations• Hemorrhoidal Preparations• Sleep Preparations• Stimulants• Appetite Suppressants• Insulin Preparations• Artificial Sweeteners• Miscellaneous OTCs

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OTC BREASTFEEDING COUNSELING GUIDELINES•Avoid taking OTC medications for which safer

products are available.•Avoid taking OTC medications for which little

breastfeeding information is available.•Avoid taking combination OTCs, which are those

with multiple ingredients (it is better for the mother to take an OTC that has the one or two specific ingredients that will treat her specific condition; there is no need for the mothers or nurslings to be exposed to unnecessary ingredients).

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OTC BREASTFEEDING COUNSELING GUIDELINES• Avoid taking extra strength forms of OTC medications

(there is no need for the nursling to be exposed to extra amounts of a drug when it is not needed).

• Avoid taking long-acting OTC medications (there is no need for the nursling to be exposed to a drug for a longer period of time, especially if an adverse reaction is possible in the nursling).

• The mother should know about possible side effects that might occur in her nursling, as well as herself.

• If possible, as with prescription drugs, the mother should use a nondrug approach for treating her symptoms.

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CONSIDERATIONS (See Nice Articles and Books): Herbals (Major Galactogogues)

•Chaste Tree•Fennel•Fenugreek•Garlic•Goat's Rue•Milk Thistle / Blessed Thistle

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CONSIDERATIONS (See Nice Articles and Books): Herbals (Minor Galactogogues)

•Anise•Borage•Alfalfa•Caraway•Coriander•Dandelion•Dill

•Marshmallow•Nettle•Hops•Oat Straw•Red Clover•Red Raspberry•Vervain

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CONSIDERATIONS (See Nice Articles and Books): Herbals

• Analgesics Bugleweed, Comfrey

• Headache (Migraine) AgentsFeverfew

• Anti-Anxiety Agents Indian Snakeroot, Kava Kava, Passionflower, St. John’s Wort, Valerian

• Stimulants Ginseng Root, Siberian Ginseng, Ginkgo Biloba, Angelica Root / Dong Quai

• Sleep Preparations Melatonin (Not Herbal)

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CONSIDERATIONS (See Nice Articles and Books): Herbals

• Cough, Cold, and Allergy Products Coltsfoot, Echinacea, Elder Flower

• Gastrointestinal AgentsAloe, Buckthorn, Cascara Sagrada, Chamomile,

Flaxseed, Licorice, Psyllium Seed, Rhubarb, Senna• Nausea and Vomiting Preparations

Ginger• Lipid Lowering Agents

Soy Lecithin• Urinary Tract Preparations

Goldenrod, Petasites, Uva Ursi

CONSIDERATIONS: Recreational Drugs•Amphetamine / Methylphenidate•Marijuana•Cocaine•Phencyclidine•Narcotics•Caffeine•Alcohol•Nicotine

Recommendations for Recreational Drug Use (See Handout)

•Drugs’ Effects•Social Considerations•Physician Recommendations•Alcohol Use Facts•PLUS: Do NOT want social services taking

baby away from mother

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RECREATIONAL DRUGSAmphetamine / Methylphenidate

• Levels in breast milk difficult to obtain due to large volume of distribution

•Possibility of irritability or poor sleep pattern•Abuse: hypertension, palpitations, tachycardia, over

stimulation, motor incoordination, tremor, restlessness

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RECREATIONAL DRUGSCocaine

•Apnea and seizures in breastfed infant who ingested cocaine which was applied topically as anesthetic

•Abuse: tachycardia, tachypnea, hypertension, irritability, tremulousness

•One of most dangerous of all drugs of abuse

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RECREATIONAL DRUGSPhencyclidine

•Potent hallucinogen• Long half-life of metabolites•One of most dangerous of all drugs of abuse

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RECREATIONAL DRUGS

Narcotics

•Codeine, Morphine, Meperidine, Heroin • Large doses can cause dependence and withdrawal

symptoms in nurslings•Use proper withdrawal techniques

Wean Breastfed Baby Off Narcotics• There are several ways to “wean” a baby off narcotics to avoid

withdrawal symptoms:1. Use of Diluted Tincture of Opium (DTO) in the infant, which

would be the least preferred2. Gradually wean the baby and maintain the narcotic dose level,

which is better, but not the most preferred3. Gradually reduce the narcotic dose while maintaining

breastfeeding, which the best option• During these processes, the mother may use Suboxone or

methadone.• Methadone can be used safely at doses above 100 mg daily for

over 30 days, if necessary, while the mother is breastfeeding

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RECREATIONAL DRUGSCaffeine

•Even though clearance of caffeine in infants is markedly reduced, amounts of caffeine ingested by breastfeeding children is small, if reasonable amounts of coffee, tea, or colas are used by mother (1 to 2 cups per day)

•Mothers of newborns, and in particular of premature newborns, should avoid caffeine

•Note: Caution if taking theophylline also (Why?)

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RECREATIONAL DRUGSAlcohol (See Handout)

• 1 to 2 cocktails, glasses of wine, or bottles of beer: Usually insignificant levels

• Odor of alcohol in milk may cause infants to consume significantly less milk

• Excessive, chronic drinking: Mild sedation to deep sleep, hypoprothrombinemic bleeding

• Caution: Intoxicated mothers should not breastfeed; chronic alcoholics should not breastfeed

• Because of rational use of alcohol is possible during breastfeeding, the use of Alcohol Breast Milk Tests is a complete waste of money, time, and effort.

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RECREATIONAL DRUGSMarijuana

•Tetrahydrocannabinol (THC) concentrated in breast milk and is absorbed by the nursing baby

• Long-term effects may occur (both mother and baby)

Schedule I Controlled Substances•Substances have a high potential for abuse, have no

currently accepted medical use in treatment in the U.S., and have a lack of accepted safety for use under medical supervision

•Marijuana is Schedule I

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Marijuana Consequences•CONSEQUENCES• Mother also potentially abusing other drug substances: marijuana users

usually do• Exposure to marijuana smoke is potentially hazardous and toxic as is

cigarette smoke• Current evidence indicates that marijuana during lactation may adversely

affect neurodevelopment, especially during critical brain growth during adolescent maturation

• Marijuana impacts neuropsychiatric, behavioral, and executive functioning, which may affect future adult productivity and lifetime outcomes (delinquency, depression, and substance abuse)

• Law passed in States, which makes recreational use of marijuana legal render toxicology interpretation complex (is mother using recreational and/or medical marijuana “legally” or illicitly and thus exposing breastfed baby to “legal” or illicit marijuana?)

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Hopalong Cassidy

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RECREATIONAL DRUGS•From both a philosophical and scientific viewpoint,

recreational drugs of abuse should be contraindicated during breastfeeding as they are hazardous, not only to the nursling, but to the mother as well.

fjncat@hotmail.com

Thank YOU for your attention and participation

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