Transcript Léky a kojení

Drugs and lactation
Jiří Slíva, MD., Ph.D.
Number of breast-feeded
children in the U.S.
AAP, 2005
Lactation and adherence to
treatment

cca 90 % of women take some medication during the first week after
delivery

some medicaments, not exactly contraindicated during pregnancy, can
decrease the intensity of lactation

women tend to disrupt lactation in case of short-term therapy (e.g.
antimicrobial agents), or they are non-compliant to prescribed medication

approximately 7 % of women disrupt lactation

up to 15 % of women do not start taking ATBs at all
Frequency of ADRs in lactating
women

prospective trial (n = 838) with breast-feeded children, whose mothers
were taking various preparations

no serious adverse reaction was recorded
however


11.2 % of women described non-serious ADRs – women were using:

antibiotics (19.3 %)

analgesics (11.2 %)

antihistaminics (9.4 %)

sedatives/antidepressants/antiepileptics (7,1 %)
commonly recorded postantibiotic diarrhea, drowsiness after strong
analgesics, antiepileptics, antidepressants, or irritability after
antihistaminics
Data on file
Transfer of drugs to maternal milk
depends on

pharmacokinetics of drug in maternal body

perfusion of mammary gland

milk composition

physico-chemical properties of drug

pH of both plasma and milk

amount of milk synthesis
Ad pH value


average plasma pH is 7.4
average pH of breast milk is lower at 7.2
thus…




drugs that are weakly basic tend to concentrate to a greater extent in
the more weakly acidic breast milk, as opposed to the less acidic
plasma since acids attract bases
weak bases are nonionized in the maternal plasma => increased ability
to be transferred into breast milk
weak acids are ionized in the maternal plasma => low diffusion into
breast milk
i.e., antihistamines and erythromycin, drugs that are weak basics,
would be more likely to cross cell membranes from maternal plasma
into breast milk than would penicillins, which are weak acids
Transfer of drugs to maternal
milk

almost every drug crosses into maternal milk

mostly via passive diffusion (e.g. H2 blockers, penicillins, nitrofurantoin
and others.)

also via active transport (e.g. cimetidine)

transcellular diffusion

breast-feeding can protect from abstinence syndrome in neonates,
whose mothers were treated by barbiturates etc.
Drugs affecting milk formation
Decrease








bromocriptine
estrogens
androgens
antihistaminics
barbiturates
apomorphine
levodopa
pyridoxine
Increase

metoclopramide

reserpine

imipramine

fenothiazine

sulpirid

TSH
Drugs contraindicated during
breast-feeding

Cytostatics – immunosuppression, neutropenia, influence on growth?,
cancerogenesis?

Abused drugs – (amphetamine, cocaine, heroin, marijuana, LSD,
alcohol, nicotine) – influence of CNS, maternal behavior

Ergot alcaloids – (bromocriptine decreases lactation, ergotamine – risk
of vomiting, diarrhea, cramps)

Iodides – risk of struma, hypothyreosis

Radioactive isotopes

Gold

Lithium – high concentration in maternal milk, possible influence of CNS

Estrogens (oral contraceptives)

Thiouracile – risk of struma, thyreosuppression, agranulocytosis
Drugs deserving increased
caution

Drugs affecting CNS – antidepressants, antipsychotics,
benzodiazepines

Drugs with recorded serious ADRs
aspirin (metabol. acidosis), atenolol (beta-blocker), carbamazepine
(sedation, hyperexcitability, cholestat. hepatitis), clemastine
(hyperexcitability, drowsiness), phenobarbital (sedation,
methaemoglobinemia), sulfasalazine (bloody diarrhea), metronidazole
(potentially cancerogenic), TTC
Safe drugs during
pregnancy
Antibiotics/chemotherapeutics

amoxicilline, phenoxymethylpenicilline, benzylpenicilline,
chloramphenicol, ciprofloxacine, clindamycine, doxycycline,
gentamicine, nitrofurantoin, metronidazole or vancomycine easily
cross to maternal milk

according to available data, tetracyclins, chloramphenicol or
aminoglycosides, eventually quinolones, can be used in specific
cases, but mostly contraindicated
Antihypertensives

ACE inhibitors, methyldopa, beta-blockers or
calcium ion channel blockers are compatible
with breastfeeding, i.e. they do not decrease
blood pressure of children
Antihistaminics

risk of irritability of children
Caffeine

in common doses fully compatible with
breastfeeding

higher doses => risk of insomnia or irritation of
children

(half-life of caffeine: 3 to 7 hours)
NSAIDs, acetaminophen

Ibuprofen – compatible with breast-feeding,

Acetylsalicylic acid – compatible with breast-feeding expect of
higher doses (risk of metabolic acidosis),

Paracetamol – compatible with breast-feeding. Currently, it is
discussed in relation with increased of higher prevalence of allergic
rhinoconjunctivitis
PREDNISON IN PAEDIATRIC
PRAXIS AND ITS
MAGISTRALITER
PREPARATION
Indications of prednisone











Respiratory system
Allergy
Nephrology
Oncology
Rheumatology
Haematology
Dermatology
Endocrinology
Ophthalmology
Gastroenterology
Immunology

Common dosis pro
infantibus ranges
from 5 to 60
mg/day
Corticosteroids for children
available in the Czech Republic

Prednisone
 Prednison tbl. 5 a 20 mg
 Rectodelt rect. supp. 100 mg
---------------------------- Methyl-prednizolone:


Dexamethasone:




Medrol tbl., Solu-Medrol i.v.
Dexamethason supp. (IVLP)
Dexamed, Dexona inj.
Fortecortin tbl.
Hydrocortisone

Hydrokortison inj., tbl.
Oral dose 5.0 mg prednisone is equal to 5.0 mg
prednisolone, 4.0 mg triamcinolonu, 0.6 mg
betamethasone, 0.75 mg dexamethasone a 20.0 mg
hydrocortisone
Prednisone suspension
Raitt, J. R., Hotaling, W. H.:
Preparation of stable
prednisone suspension,
Amer. J. Hosp. Pharm.
30:923-924 (Oct.) 1973.
Prescription
Rp.
Prednisoni plv.…………………………..1,0 g
Natrii benzoati 0,1%..............40,0 ml
Tragacant-acacii mxt……………….20,0 ml
Tragacant 3%
Acacia 3%
Natrii benzoat 0,1%
Anisi (foeniculi) ol. 0,025%
Sirupi ad…………………..…….100,0 ml
Sirupi simplicis 67 %
Sirupi aurantii 33 %
Economic evaluation
Vial
(100 ml)
CZK
1
189,75
2
161,88
3
152,59
4
150,88
5
147,51
6
147,09
7
145,23
8
143,83
9
142,74
10
141,86
Total price
Price per 5 mg
Prednison tbl
20x5mg
30.10 CZK
1.50 CZK
Prednison susp.
100ml
189.75 CZK
0.95 CZK
Useful URLs

LACTMED: http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT

TOXNET: http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT

WHO: http://whqlibdoc.who.int/hq/2002/55732.pdf

AAP: http://www.aap.org/healthtopics/breastfeeding.cfm
Questions for independent
work:
1.
Try to decide: which of molecules will be transfered into maternal milk
easier – warfarin or sumatriptan (based on plasma protein-binding?)
2.
Try to find decide, how salicylates (i.e. acetylsalicylic acid etc.) cross
into maternal milk
3.
Try to find/recommend oral antiseptic drug compatible with both
breast-feeding and pregnancy (AISLP, Micromedex etc.)
4.
What kind of drugs (active substance/plants) are used/recommended
in order to stimulate lactation?
5.
Prescribe 10 suppositories with domperidone for infant (Dosis
Therapeutica Singula = 10 mg)
Brand
Content
Dosage
Bylinný čaj s jestřabinou
pro kojící maminky
Meduňková nať, plod kopru,
plod fenyklu, nať jestřabiny
a nať dobromyslu
2–3x denně po celé období
kojení
Čaj pro kojící matky
Nať jestřabiny, plod kmínu,
fenyklu,
nať
meduňky,
zlatobýlu,
violky
trojbarevné, list jitrocele.
2–3x denně po celé období
kojení
ČAJánek Na podporu kojení
Nať jestřabiny lékařské, květ
ibišku súdánského, plod
fenyklu, listy maliníku, nať
levandule lékařské
2–3x denně po celé období
kojení
Laktační –
porcovaný
bylinný
čaj
fenykl plod, anýz plod, kopr
plod, aronie plod, kmín
plod,
jestřabina
nať,
mateřídouška nať, kopřiva
list, heřmánek květ
3x denně po celé období
kojení
Laktační
sypaný
bylinný
čaj
dtto
3 x denně po celé období
kojení. Nálev se připravuje
z obsahu 1 čajové lžičky
přelitím 1/4 l vroucí vody a
nechá se v zakryté nádobě
15 min odstát.
Laktofyt – bylinný sirup
voda, cukr, bylinné extrakty
z anýzu, fenyklu, kmínu,
pískavce, bazalky, meduňky
a ibišku, kyselina jablečná,
sorban draselný
Užívá se jako sirup s vodou
dle chuti.
WELEDA Čaj pro podporu
kojení
kopřiva, semena
fenyklu a kmínu
3–6x denně po celé období
kojení
–
anýzu,