ACE
inhibitors
Antihypertensive
CATEGORY: C first trimester
CATEGORY: D second and third trimesters
2nd and 3rd trimester use is associated with hypocalvaria, and renal defects related to fetal hypotension and decreased
renal perfusion. The latter may result in oligohydramnios.
BREAST FEEDING:Compatible.Excretion into milk negligible.
NEONATAL SIDE EFFECTS:At delivery
renal failure,hypotension
CERCA LETTERATURA
ADDITIONAL READING: Angiotensin-Converting Enzyme (ACE)Inhibitors and Pregnancy
1996 Illinois Teratogen Information Service
Acetaminophen (paracetamol
Analgesic and antipyretic.Cyclooxygenase inhibitor. Molecular weight: 151.16
CATEGORY:
B [1]
Appears to cross the human placenta [2]
Three studies involving more than 10,000 newborns exposed to acetaminophen
during the first trimester did not find an association between acetaminophen
and major malformations [1,3,4].
In a prospective study of 300 women who had self-administered an overdose
of (acetaminophen) paracetamol, either alone, or as part of a combined
preparation there were 219 liveborn infants with no malformations, 61 of whom
had been exposed in the first trimester. None of the mothers died. Eleven
liveborn infants had malformations; none was exposed in the first trimester.
There were seven full-term infants with neonatal problems that seem unrelated
to paracetamol exposure. Six premature infants also had neonatal problems,
which were more likely to be related to their degree of prematurity rather
than paracetamol exposure [5].
Char et al reported a case of severe maternal anemia and fatal kidney
disease in the newborn following a continuous high daily dosage of
acetaminophen [6].
Although the above studies are, overall, reassuring the findings of a
retrospective study evaluating the relation between maternal use of cough/cold/analgesic
medications and risks of gastroschisis and small intestinal atresia (SIA)
raise questions about interactions between acetaminophen and
pseudoephedrine. Werler MM, et al. , found that among mothers of
206 infants with gastroschisis and 126 mothers of infants with small
intestinal atresia infants with gastroschisis had an increased risk (odds
ratio = 1.5) of having been exposed to acetaminophen during gestation. The
risk for gastroschisis was increased further (odds ratio = 4.2) among infants
who had been exposed to pseudoephedrine combined with acetaminophen. The risk
of small intestinal atresia was increased for use of pseudoephedrine in
combination with acetaminophen (odds ratio = 3.0) [7].
Gastroschisis is a congenital defect of the anterior abdominal wall
characterized by an opening beside the umbilical cord that allows bowel to
protrude. Gastroschisis is thought to arise from disruption of blood flow
to the affected abdominal wall [8]. The defect is uncommon and occurs in the
general population with an incidence of 2.4 to 3.2 per 10,000 births in
the general population with the highest incidence in women 15-19 years of age
( 26.5 per 10,000 births) [9,10]. The uncommon occurrence of gastroschisis
should be considered when counseling patients or interpreting the
literature as to the increased risk for gastroschisis after any particular
drug ingestion.
BREAST FEEDING: The mean milk/plasma ratio was 0.76 in 3 lactating
women after ingestion of a single 500 mg dose of paracetamol [11]. Another
study found peak milk levels were achieved by one to two hours after a
single oral dose of 650 mg. Assuming an infant ingested 90 ml milk at 3, 6,
and 9 hours after maternal ingestion of paracetamol, the amount of paracetamol
available for ingestion would have been less than 0.23% of the maternal dose
[12].
The American Academy of Pediatrics has classified acetaminophen (paracetamol )
as a drug "Usually Compatible With Breastfeeding" [13].
NEONATAL SIDE EFFECTS: One case of rash after breast feeding [13].
SEARCH
LITERATURE
1. Briggs GG,Freeman RK, Yaffe SJ, Drugs in
Pregnancy and Lactation 6th edition,Baltimore, MD: Williams
& Wilkins,2002 p 6-9
2. Levy G, et al. Letter: Evidence of placental transfer of
acetaminophen.Pediatrics. 1975 ;55:895. MEDLINE
3.Heinonen OP et al: Birth Defects and Drugs in Pregnancy Littleton,
Publishing Sciences Group, 1977, pp 286-295
4. Aselton P, et al First-trimester drug use and congenital disorders.Obstet
Gynecol. 1985;65:451-5. MEDLINE
5. McElhatton PR, Sullivan FM, Paracetamol overdose in pregnancy analysis of
the outcomes of 300 cases referred to the Teratology Information Service.
Reprod Toxicol. 1997;11:85-94. MEDLINE
6.Char VC, et al Letter: Polyhydramnios and neonatal renal failure--a possible
association with maternal acetaminophen ingestion.J Pediatr. 197586:638-9.MEDLINE
7.Werler MM, et al Maternal medication use and risks of gastroschisis and
small intestinal atresia. Am J Epidemiol. 2002;155:26-31 MEDLINE
8. Hoyme HE, et al. ;The vascular pathogenesis of gastroschisis: intrauterine
interruption of the omphalomesenteric artery.J Pediatr. 1981;98:228-31. MEDLINE
9. Reid KP, et al., The epidemiologic incidence of congenital gastroschisis in
Western Australia. Am J Obstet Gynecol. 2003;189:764-8. MEDLINE
10. Nichols CR, et al., Rising incidence of gastroschisis in teenage
pregnancies. J Matern Fetal Med. 1997;6:225-9.MEDLINE
11. Bitzen PO,et al Excretion of paracetamol in human breast milk.Eur J Clin
Pharmacol. 1981;20:123-5. MEDLINE
12. Berlin Jr CM, et al. Disposition of acetaminophen in milk, saliva, and
plasma of lactating women.Pediatr Pharmacol (New York).1980;1:135-41. MEDLINE
13.Transfer
of drugs and other chemicals into human milk. Pediatrics. 2001;108:776-89.
Acetazolamide
Diuretic, Carbonic anhydrase inhibitor
CATEGORY: C
Sacrococcygeal teratoma has been reported in an infant born to a mother treated with acetazolamide until the 19th week of pregnancy [1].
The Collaborative Perinatal Project found no increase in major or minor fetal anomalies in the infants of 1,024 women exposed to acetazolamide at any time during pregnancy including 12 infants exposed during the 1st trimester[G10].
However, the sample size is too small to evaluate the risk for uncommon conditions such as sacrococcygeal teratoma which has an incidence of 1 in 35,000 to 40,000 live births [2].
Acetazolamide should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.
BREAST FEEDING:Excreted into human breast milk [3]. Compatible [G3].
NEONATAL SIDE EFFECTS: Renal tubular acidosis has been reported in a preterm boy shortly after birth in a mother treated with oral acetazolamide[4].
CERCA LETTERATURA
1. Worsham F, Beckman EN and Mitchell EH. Sacrococcygeal teratoma in a neonate. Association with maternal use of acetazolamide. J Am Med Assoc. 240:251-2, 1978.
MEDLINE
2. Havranek P, Hedlund H, Rubenson A, Guth D, Husberg M, Frykberg T, Larsson LT. Sacrococcygeal teratoma in Sweden between 1978 and 1989. J Pediatr Surg. 1992;27:916-918.
MEDLINE
3. Soderman P, Hartvig P, Fagerlund C. Acetazolamide excretion into human breast milk. Br J Clin Pharmacol. 1984 May;17(5):599-600.
MEDLINE
4. Ozawa H, Azuma E, Shindo K, Higashigawa M, Mukouhara R, Komada Y. Transient renal tubular acidosis in a neonate following transplacental acetazolamide.
Eur J Pediatr. 2001 May;160(5):321-2.
MEDLINE
Acyclovir
Antiviral
CATEGORY: B
Crosses placenta (maternal:cord ratio of ~ 1.3 after IV/PO exposure).
In a prospective epidemiological registry 1st trimester exposure to acyclovir in 749 pregnancies resulted in no increase in major or minor fetal anomalies.
However, the manufacturer cautions, the small size of the registry is insufficient to evaluate the risk for less common defects or to permit reliable or definitive conclusions regarding the safety of acyclovir in pregnant women and their developing fetuses. [G6].
BREAST FEEDING:Compatible. Concentrated in human milk. Compatible [G3].
NEONATAL SIDE EFFECTS: None reported.
CERCA LETTERATURA
5.Breastfeeding and Maternal Medication. Recommendations for Drugs in the
Eleventh WHO Model list of Essential Drugs. pp 12 World Health Organization, 2002. 20 Avenue Appia ,1211 Geneva ,Switzerland
(PDF file)
7. Transfer of drugs and other chemicals into human milk. Pediatrics. 2001 Sep;108(3):776-89. Review.
Adenosine
Antiarrhythmic, Miscellaneous
CATEGORY: C
There are no adequate human studies.
BREAST FEEDING:
NEONATAL SIDE EFFECTS:None reported
at birth.
CERCA LETTERATURA
Albuterol
Antiasthmatic. Beta 2 -adrenergic bronchodilator.
CATEGORY: C
Crosses placenta. 1st trimester exposure
in 1090 infants resulted in no increase in major or minor anomalies .
BREAST FEEDING:Compatible.
NEONATAL SIDE EFFECTS:At birth hypoglycemia.
Agitation, GI upset after breast feeding
CERCA LETTERATURA
Alfentanil
Opiate Agonist
CATEGORY: C
Crosses placenta. There are no adequate
human studies.
BREAST FEEDING:Compatible.Excretion into milk minimal.
NEONATAL SIDE EFFECTS:At birth respiratory depression.
CERCA LETTERATURA
Alendronate
Bone Metabolism, Bisphosphonate
CATEGORY:C
There are no adequate human studies.
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Allopurinol
Gout, Uricosuric
CATEGORY: C
There are no adequate human studies.
BREAST FEEDING: Compatible [G3].
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Alprazolam
Antianxiety, Benzodiazepine
CATEGORY: D
No data on placental passage . However,
benzodiazepines as a class freely cross the placenta and may accumulate
in the fetus. 1st trimester exposure to alprazolam specifically in 542
infants, studied prospectively, resulted in no increase in major or minor
anomalies, or rates of miscarriage.
BREAST FEEDING: The American Academy of Pediatrics has classified alprazolam as a drug "for which the effect on nursing infants is unknown but may be of concern" [G3].
NEONATAL SIDE EFFECTS:Withdrawal,neonatal flaccidity and respiratory problems at birth.
CERCA LETTERATURA
ADDITIONAL READING: Update:Benzodiazepines in Pregnancy
1999 Illinois Teratogen Information Service
Amantadine
Antiviral
CATEGORY: C
In a surveillance study of Michigan Medicaid patients 1st trimester exposure in 64 infants resulted in 5 birth defects (3.1 expected)[1].
The sample size is too small to draw firm conclusions.
BREAST FEEDING: The manufacturer reports amantadine is excreted in human milk, and recommends the drug not be used in nursing mothers [G3].
NEONATAL SIDE EFFECTS:Potential release of levodopa, urinary retention, vomiting, and rash after breast feeding.
CERCA LETTERATURA
1.Rosa F: Amantadine pregnancy experience. Reprod Toxicol. 1994 Nov-Dec;8(6):531.
MEDLINE
Amikacin
Antibiotic, Aminoglycoside
CATEGORY: C
Crosses placenta. There are no adequate
human studies. In utero aminoglycoside ototoxicity has not been reported
to date with amikacin.
BREAST FEEDING:Compatible.Excretion
into milk negligible. Oral absorption is poor.
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Amiloride
Potassium Sparing Diuretic
CATEGORY: B
1st trimester exposure in 28 infants resulted in a 2 fold increase in major birth defects, but the
sample size
is to small to draw firm conclusions.
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Aminocaproic
acid
Hemostatic
CATEGORY: C
There are no adequate human studies.
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Aminoglycosides
Antibiotic
CATEGORY: C
All cross placenta.In utero aminoglycoside
ototoxicity has been reported to date with kanamycin, and streptomycin,
but not with amikacin, gentamicin nor tobramycin.
BREAST FEEDING: Compatible [G3].
NEONATAL SIDE EFFECTS:Potentiation
of MgSO4-induced neuromuscular blockade postpartum. Diarrhea after breast
feeding.
CERCA LETTERATURA
ADDITIONAL READING: Antibiotics and Pregnancy
1995 Illinois Teratogen Information Service
Aminophylline (see Theophylline)
Antiasthmatic/Bronchodilator
CATEGORY: C
BREAST FEEDING:Compatible
NEONATAL SIDE EFFECTS:Irritability
CERCA LETTERATURA
Amiodarone
Antiarrhyythmic
CATEGORY: D
Crosses placenta. There are no adequate
human studies. Congenital hypothyroidism described in second trimester
(the drug is 38% iodine by weight).Fetal bradycardia.
BREAST FEEDING:Excretion into milk significant.Elimination half life is up to 58 days.The American Academy of Pediatrics has classified amiodarone as a drug "for which the effect on nursing infants is unknown but may be of concern" [G3].
NEONATAL SIDE EFFECTS:May accumulate in infant with breast feeding. Possible hypothyroidism.
CERCA LETTERATURA
Amitriptyline
Antidepressant, Tricyclic
CATEGORY: Assigned to category D in past.
Presently carries the following precautions: Amitriptyline has been shown to cross the placenta. Although a causal relationship has not been established, there have been a few reports of adverse events, including CNS effects, limb deformities, or developmental delay, in infants whose mothers had taken amitriptyline during pregnancy. Amitriptyline should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.
1st trimester exposure in 467 infants resulted in no increase in major or minor anomalies [G1].
BREAST FEEDING: The American Academy of Pediatrics has classified amitriptyline as a drug "for which the effect on nursing infants is unknown but may be of concern" [G3].
NEONATAL SIDE EFFECTS:Potential for
urinary retention.
CERCA LETTERATURA
Amlodipine
Antihypertensive, Calcium channel
blocker
CATEGORY:C
There are no adequate human studies.
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Amoxapine
Antidepressant,dibenzoxazepine
CATEGORY: C
1st trimester exposure in 19 infants
resulted in a threefold increase in major anomalies ,but the
sample size
is to small to draw firm conclusions.
BREAST FEEDING: The American Academy of Pediatrics has classified amoxapine as a drug "for which the effect on nursing infants is unknown but may be of concern" [G3].
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Amoxicillin
Antibiotic, Penicillin
CATEGORY: B
1st trimester exposure in 8,538 infants
resulted in no increase in major or minor anomalies
BREAST FEEDING: Compatible [G3].
NEONATAL SIDE EFFECTS:Possible diarrhea.
CERCA LETTERATURA
ADDITIONAL READING: Antibiotics and Pregnancy
1995 Illinois Teratogen Information Service
Amoxicillin/Clavulanate
Antibiotic, Penicillin
CATEGORY:B
BREAST FEEDING:Compatible
NEONATAL SIDE EFFECTS:Diarrhea
CERCA LETTERATURA
Amphetamine
Respiratory and Cerebral Stimulant
CATEGORY: C
Nonteratogenic when used under medical
supervision (narcolepsy, appetitie suppressant). Illicit use is associated
with IUGR , preterm labor, and fetal cerebrovascular accidents.
BREAST FEEDING:Contraindicated
NEONATAL SIDE EFFECTS:Withdrawal in infants born to amphetamine addicted mothers.
CERCA LETTERATURA
Amphotericin B
Antifungal
CATEGORY: B
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Ampicillin
Antibiotic, Penicillin
CATEGORY: B
BREAST FEEDING:Compatible
NEONATAL SIDE EFFECTS:Diarrhea
CERCA LETTERATURA
ADDITIONAL READING: Antibiotics and Pregnancy
1995 Illinois Teratogen Information Service
Aspartame
CATEGORY: NA
BREAST FEEDING:Compatible
NEONATAL SIDE EFFECTS:Caution in PKU
carriers
CERCA LETTERATURA
Aspirin
Nonsteroidal Antiinflammatory Agent
CATEGORY: C in low dose (< 150
mg/day)
CATEGORY: D in standard doses
All NSAIDs used near term may cause closure of the ductus arteriosus, and inhibit labor. Oligohydramnios after prolonged use is a common complication.
BREAST FEEDING:The American Academy of Pediatrics has classified aspirin as a drug "which should be given to nursing mothers with caution" [G3].
The WHO Working Group on Human Lactation classified the salicylates as unsafe for use by nursing women [G8].
NEONATAL SIDE EFFECTS:Altered platelet
function.Dose related metabolic acidosis
CERCA LETTERATURA
Atenolol
Antihypertensive, Beta blocker
CATEGORY: D
Intrauterine growth retardation if
started in 2nd trimester.
BREAST FEEDING: The American Academy of Pediatrics has classified atenolol as a drug "which should be given to nursing mothers with caution" [G3].
NEONATAL SIDE EFFECTS:Possible hypotension.
CERCA LETTERATURA
Atropine
Antimuscarinic/Antispasmodic
CATEGORY:C
BREAST FEEDING: Compatible [G3].
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Atorvastatin
Antilipemic, HMGCoA Reductase inhibitor
CATEGORY:X
Inadvertent exposure to other HMG-coA reductase inhibitors during pregnancy has not been shown to increase the risk of adverse pregnancy outcome[1].
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
1. Manson JM, Freyssinges C, Ducrocq MB, Stephenson WP: Postmarketing surveillance of lovastatin and simvastatin exposure during pregnancy. Reprod Toxicol 1996;10:439-66.
MEDLINE
Azathioprine
Antineoplastic
CATEGORY:D
CERCA LETTERATURA
Azithromycin
Azithromycin is an azalide antibiotic related to erythromycin. Molecular
weight: 749.0
CATEGORY:B
"Reproduction studies have been performed in rats and mice at doses up
to moderately maternally toxic dose concentrations (i.e., 200 mg/kg/day).
These doses, based on a mg/m 2 basis, are estimated to be 4 and 2 times,
respectively, the human daily dose of 500 mg. In the animal studies, no
evidence of harm to the fetus due to azithromycin was found." [1]
Azithromycin appears to have limited transplacental transfer [2] in humans
with high sustained levels within myometrium, adipose, and placental tissue
[3].
Reports on the use of azithromycin during the first trimester in human
pregnancy are scarce. The preponderance of the literature describes the use of
azithromycin during the second and third trimesters of pregnancy.
In an observational study of newly marketed drugs prescribed in England
azithromycin was taken during the first trimester in eleven pregnancies. One
patient chose to have an elective abortion. The remaining mothers delivered
ten normal infants [4]. There is one case report of a woman treated with
oral azithromycin at approximately 3 weeks' gestation for acute scrub
typhus. She subsequently miscarried three weeks after treatment. This
individual had a history of two previous spontaneous abortions. Her underlying
illness and obstetrical history may have been contributing factors leading to
her miscarriage[5].
In three additional case reports of pregnant women treated for scrub typhus
the women were treated with azithromycin between 19 and 24 weeks’ gestation.
Two of these women had given birth at term to healthy infants at one year
follow up and one woman was lost to follow up [5,6] .
Azithromycin has also been used to successfully treat Chlamydia during the
second and third trimesters of pregnancy (using a single 1 gram oral dose)
[7-11]. Primary outcomes reported for most studies were success of
treatment and maternal side effects. No adverse neonatal outcomes were
specifically reported by one study of 42 pregnancies [9].
A single 1 gram oral dose of azithromycin was ineffective in reducing lower
genital colonization of Ureaplasma urealyticum in women with preterm labor or
preterm premature rupture of membranes (PROM) between 22 and 34 weeks'
gestation [12].
In a retrospective study Mahon BE, et al reported a higher incidence of
infantile hypertrophic pyloric stenosis in the infants of mothers who had used
macrolide (erythromycin, azithromycin, and clarithromycin) antibiotics during
the last ten weeks of pregnancy. However, the data did not reach
statistical significance [13]. Cooper WO et. al. reviewed the files of 260,799
mother/infant pairs enrolled in the Tennessee Medicaid/TennCare from
1985-1997. For nonerythromycin macrolide use at any time during
pregnancy, there was an association of pyloric stenosis with maternal non
erythromycin macrolide prescriptions; odds ratio of 2.77.
Nonerythromycin macrolides included lincomycin, clindamycin, clarithromycin,
azithromycin, and dirithromycin[14].
BREAST FEEDING: Azithromycin appears to be excreted into human milk.
In one case report a mother took an initial dose of 1 gram of oral
azithromycin. Approximately 60 hours later she resumed taking azithromycin at
a dose of 500 mg daily for an additional three doses. One hour after the first
500 mg dose the breast milk concentration of azithromycin was 1.3
micrograms/mL. Thirty hours after the third dose of 500 mg the breast milk
concentration was 2.8 micrograms/mL. Maternal serum levels were not included
in the report.
The predicted dose of azithromycin to the infant was calculated from the
equation:
Absorbed dose = Drug concentration in milk x Volume of milk consumed x
Bioavailability
Where:
Drug concentration in milk = 2.8 micrograms/mL
Volume of milk consumed = 150 ml/kg/day (in this case the infant weighed 3.1
kg)
Bioavailability = 37%
Absorbed dose = 482 micrograms/day.
The authors of the report concluded that azithromycin appears to accumulate
in breast milk. However, this may not be clinically significant given the low
dose delivered to the infant. [15].
SEARCH
LITERATURE
1. Physicians
Desk Reference 57th ed. Montvale, NJ: Thomson PDR; 2004: 2684
2. Heikkinen T,et. al., The transplacental transfer of the macrolide
antibiotics erythromycin, roxithromycin and azithromycin. BJOG.
2000;107:770-5. MEDLINE
3. Ramsey PS,et. al., Maternal and transplacental pharmacokinetics of
azithromycin. Am J Obstet Gynecol. 2003;188:714-8. MEDLINE
4. Wilton LV, Pearce GL, Martin RM et al: The outcomes of pregnancy in women
exposed to newly marketed drugs in general practice in England. Br J Obstet
Gynaecol 105:882-889, 1998. MEDLINE
5. Watt G, et al. Azithromycin activities against Orientia tsutsugamushi
strains isolated in cases of scrub typhus in Northern Thailand. Antimicrob
Agents Chemother. 1999;43:2817-8. MEDLINE
6. Choi E-K, Pai H: Azithromycin therapy for scrub typhus during pregnancy.
Clin Infect Dis 27:1538-1539, 1998. MEDLINE
7. Bush MR, Rosa C Azithromycin and erythromycin in the treatment of cervical
chlamydial infection during pregnancy. Obstet Gynecol. 1994 ;84:61-3. MEDLINE
8. Wehbeh HA, Single-dose azithromycin for Chlamydia in pregnant women. J
Reprod Med. 1998;43:509-14. MEDLINE
9. Adair CD, Gunter M, Stovall TG, McElvoy G, Veille JC, Erment JM. Chlamydia
in pregnancy: a randomized trial of azithromycin and erithromycin. Obstet
Gynecol 1998;91:165-8.MEDLINE
10. Jacobson GF, A randomized controlled trial comparing amoxicillin and
azithromycin for the treatment of Chlamydia trachomatis in pregnancy. Am J
Obstet Gynecol. 2001;184:1352-4 MEDLINE
11. Kacmar J,et al. ,A randomized trial of azithromycin versus amoxicillin for
the treatment of Chlamydia trachomatis in pregnancy. Infect Dis Obstet Gynecol.
2001;9(4):197-202. MEDLINE
12. Ogasawara KK and Goodwin TM Efficacy of azithromycin in reducing lower
genital Ureaplasma urealyticum colonization in women at risk for preterm
delivery. J Matern Fetal Med. 1999 ;8:12-6. MEDLINE
13. Mahon BE, Rosenman MB, Kleiman MB. Maternal and infant use of erythromycin
and other macrolide antibiotics as risk factors for infantile hypertrophic
pyloric stenosis. J Pediatr. 2001;139:380-4. MEDLINE
14. Cooper WO, Ray WA, Griffin MR. Prenatal prescription of macrolide
antibiotics and infantile hypertrophic pyloric stenosis. Obstet Gynecol.
2002;100:101-6. MEDLINE
15. Kelsey JJ et al.Presence of azithromycin breast milk concentrations: a
case report. Am J Obstet Gynecol. 1994;170:1375-6. MEDLINE
Aztreonam
Antibiotic, Misc Beta-Lactam
CATEGORY:B
No human data. No teratogenic effects
in animal studies.
BREAST FEEDING: Compatible [G3].
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Baclofen
Skeletal Muscle Relaxant
CATEGORY:C
BREAST FEEDING: Compatible [G3].
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Barbiturates
CATEGORY: D
BREAST FEEDING: Compatible [G3].
NEONATAL SIDE EFFECTS:Sedation, withdrawal
CERCA LETTERATURA
Beclomethasone
Corticosteroid; Antiasthmatic
CATEGORY: C
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
ADDITIONAL READING: Corticosteroids in Pregnancy
2000 Illinois Teratogen Information Service
Benazepril
Antihypertensive Agent, ACE inhibitor
CATEGORY: C first trimester
CATEGORY: D second and third trimesters
2nd and 3rd trimester ACE inhibitor exposure is associated with hypocalvaria, and renal defects related to fetal hypotension and decreased
renal perfusion. The latter may result in oligohydramnios.
BREAST FEEDING:Compatible.Excretion into milk negligible.
NEONATAL SIDE EFFECTS:Possible renal failure and hypotension at delivery.
CERCA LETTERATURA
Benztropine
Anti-Parkinsonnian Agent
CATEGORY:C
Possible association with cardiovascular
defects.
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Betamethasone
Corticosteroid
CATEGORY: C
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
ADDITIONAL READING: Corticosteroids in Pregnancy
2000 Illinois Teratogen Information Service
Betaxolol
Treatment of Glaucoma
CATEGORY: C
BREAST FEEDING:With caution
NEONATAL SIDE EFFECTS:Hypotension,
bradycardia
CERCA LETTERATURA
Bethanechol
Cholinergic Agent
CATEGORY: C
BREAST FEEDING:Contraindicated
NEONATAL SIDE EFFECTS:Diarrhea, abdominal
pain
CERCA LETTERATURA
Bismuth subsalicylate
Antidiarrhea Agent
CATEGORY: C
After oral administration, bismuth subsalicylate is metabolized to bismuth salts and sodium salicylate [1].
1st trimester exposure to bismuth salts in 15 infants resulted in no increase in major or minor anomalies [G10]. However, the
sample size is too small to draw firm conclusions.
Sodium salicylate and acetylsalicylic acid (Aspirin) belong to the nonsteroidal anti-inflammatory (NSAIDs) group of drugs. NSAIDs used near term may cause closure of the ductus arteriosus and inhibit labor. Oligohydramnios after prolonged use is a common complication.
BREAST FEEDING: Salicylates are excreted into breast milk. The American Academy of Pediatrics has classified salicylate as a drug "for which the effect on nursing infants is unknown but may be of concern" [G3].
The WHO Working Group on Human Lactation classified the salicylates as unsafe for use by nursing women [G8].
NEONATAL SIDE EFFECTS: Possible metabolic acidosis due to salicylate metabolite.
CERCA LETTERATURA
1.Gorbach SL. Bismuth therapy in gastrointestinal diseases.Gastroenterology. 1990 99:863-75MEDLINE
Created: 11/17/2001
Last Update: 1/3/2003
Bleomycin
Antineoplastic
CATEGORY: D
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
ADDITIONAL READING: Cancer, Chemotherapy and Pregnancy
1998 Illinois Teratogen Information Service Chemotherapy in Pregnancy
Motherisk
Bromocriptine
Treatment of Hyperprolactinemia
CATEGORY: B
BREAST FEEDING:Contraindicated
NEONATAL SIDE EFFECTS:Suppresses lactation
in mom
CERCA LETTERATURA
Brompheniramine
Antihistamine
CATEGORY:C
BREAST FEEDING: Compatible
NEONATAL SIDE EFFECTS:Agitation, poor feeding and sleeping
CERCA LETTERATURA
ADDITIONAL READING: Over the Counter Cold Medications in Pregnancy
1998 Illinois Teratogen Information Service
Budesonide
Budesonide
Corticosteroid. Molecular weight: 430.5.
CATEGORY:
B
"Budesonide produced fetal loss, decreased pup weight, and skeletal
abnormalities at subcutaneous doses of 25 mcg/kg/day in rabbits (approximately
1/3 the maximum recommended daily inhalation dose in adults on a mcg/m 2 basis)
and 500 mcg/kg/day in rats (approximately 3 times the maximum recommended daily
inhalation dose in adults on a mcg/m 2 basis).
No teratogenic or embryocidal effects were observed in rats when budesonide
was administered by inhalation at doses up to 250 mcg/kg/day (approximately 2
times the maximum recommended daily inhalation dose in adults on a mcg/m 2 basis)"
[1]
Analysis of data in the Swedish Medical Birth Registry showed no increase in the
incidence of congenital defects in a population of 2014 infants whose mothers
used budesonide during early pregnancy [2].
Data from the same registry compared 2,968 mothers who reported use of
inhaled budesonide during early pregnancy with those reporting no asthma
medication usage. The mothers who reported use of inhaled budesonide during
early pregnancy gave birth to infants of normal gestational age, birth weight,
and length, with no increased rate of stillbirths or multiple births compared to
the unexposed controls [3].
The American College of Obstetricians and Gynecologists (ACOG) and The American
College of Allergy, Asthma and Immunology (ACAAI) consider beclomethasone and
budesonide to be the inhaled steroids of choice for use during pregnancy [4].
BREAST FEEDING: "Corticosteroids are secreted in human milk. Because
of the potential for adverse reactions in nursing infants from any
corticosteroid, a decision should be made whether to discontinue nursing or
discontinue the drug, taking into account the importance of the drug to the
mother. Actual data for budesonide are lacking" [1].
SEARCH
LITERATURE
1. Physicians
Desk Reference 57th ed. Montvale, NJ: Thomson PDR; 2003: 638
2. Kallen B, Rydhstroem H, Aberg A. Congenital malformations after the use of
inhaled budesonide in early pregnancy. Obstet Gynecol. 1999 Mar;93(3):392-5. MEDLINE
3. Norjavaara E and de Verdier MG. Normal pregnancy outcomes in a
population-based study including 2,968 pregnant women exposed to budesonide.J
Allergy Clin Immunol. 2003;111:736-42. MEDLINE
4. The use of newer asthma and allergy medications during pregnancy. Position
Statement. The American College of Obstetricians and Gynecologists (ACOG) and
The American College of Allergy, Asthma and Immunology (ACAAI). Ann Allergy
Asthma Immunol. 2000;84:475-480. MEDLINE
Bumetanide
Diuretic
CATEGORY: C
BREAST FEEDING:Contraindicated
NEONATAL SIDE EFFECTS:May suppress
lactation
CERCA LETTERATURA
Bupropion
Antidepressant of the aminoketone class. Used in smoking cessation.
Molecular weight: 276.2
CATEGORY:B
"Reproduction studies have been performed in rabbits and rats at doses
up to 15 to 45 times the human daily dose and have revealed no definitive
evidence of impaired fertility or harm to the fetus due to bupropion. (In
rabbits, a slightly increased incidence of fetal abnormalities was seen in 2
studies, but there was no increase in any specific abnormality)." [1]
As of February 2003, 764 pregnancies involving exposure to bupropion
had been prospectively registered with The Glaxo Wellcome Bupropion Pregnancy
Registry. As of June 2003, 154 pregnancies were pending delivery, 213
cases were lost to follow up, and 397 cases with 401 outcomes were obtained.
The indications for use of bupropion in the latter were depression in 251
patients, smoking cessation in 95 patients, depression and smoking cessation in
16 patients, bipolar affective disorder in one patient, and unspecified in 34
patients.
Of 322 outcomes involving bupropion exposure in the first trimester there
were 261 live births without birth defects, 40 spontaneous pregnancy losses, 11
induced abortions, 1 induced abortion with evidence of Down syndrome on prenatal
testing, and 9 infants born alive with birth defects.
The defects in infants born alive included one infant with bilateral
club feet, one infant with Klinefelter's syndrome (no physical
abnormalities), and 7 infants with heart defects (1 abnormal aortic valve
thickening with mild aortic insufficiency, 1 ventricular septal defect, 1
trivial pulmonic stenosis with atrial septal defect, 1 coarctation with
ventricular septal defect, 1 thickened heart muscle, 1 pulmonary stenosis, and 1
coarctation of the aorta).
The observed proportion of birth defects in pregnancies with prenatal
exposure to bupropion in the first trimester was 3.7%.
The registry's Advisory Committee noted the increased number of prospective
reports of defects involving the heart and great vessels. Given the small sample
size and the potential bias from the large percentage of cases lost to follow up
an accurate assessment of a potential effect of bupropion on the developing
cardiovascular system could not be made. To further evaluate the possible
association of bupropion with cardiovascular defects The Committee plans
to conduct a retrospective cohort study entitled "Bupropion in Pregnancy
and the Risk of Cardiovascular and Overall Major Congenital Malformations".
(2).
Healthcare providers can obtain interim registry results and register
patients by calling the registry project office directly at 1-800-336-2176 (toll-free)
or (910) 256-0549 (collect)
BREAST FEEDING: Bupropion is excreted into human milk. In one mother
taking bupropion 100 mg three times daily peak milk concentrations occurred 2
hours after a 100 mg dose, The milk-to-plasma ratio ranged between 2.49 and 8.72
over 6 hours after after a 100-mg dose. Bupropion and its metabolites were not
detected in the infant's plasma [3]. Milk-to-plasma ratios ranged from 2.51 to
8.58 over a six-hour interval.
Baab SW et al. reported no quantifiable levels of bupropion nor its active
metabolite hydroxybupropion were found in serum samples of two breast fed
infants after maternal ingestion of either bupropion 75 mg b.i.d. or bupropion
SR 150 mg daily[4].
The infants studied in the above reports were all healthy infants at least
several months of age. These results may not be applicable to newborns or
infants with health problems.
The American Academy of Pediatrics has classified bupropion as a drug "for
which the effect on nursing infants is unknown but may be of concern" [5].
SEARCH
LITERATURE
1. Physicians
Desk Reference 57th ed. Montvale, NJ: Thomson PDR; 2003: 1680.
2. Glaxo Wellcome Bupropion Pregnancy Registry 9/1/97 – 2/28/03. Issued June
2003. Research Triangle Park, North Carolina. 13p.
3. Briggs GG, et al., Excretion of bupropion in breast milk. Ann Pharmacother.
1993;27:431-3.MEDLINE
4. Baab SW, et al. Serum bupropion levels in 2 breastfeeding mother-infant
pairs.J Clin Psychiatry. 2002;63:910-1. MEDLINE
5.Transfer
of drugs and other chemicals into human milk. Pediatrics. 2001 Sep;108(3):776-89.
Review.
INIZIO PAGINA
Buspirone
Anxiolytic, sedative, hypnotic
CATEGORY:B
BREAST FEEDING:With caution. May be of concern.
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Butalbital
Intermiediate-acting Barbiturate
CATEGORY:C
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Butoconazole
Antifungal, Topical
CATEGORY:C
1st trimester exposure in 444 infants resulted in no increase in major or minor anomalies
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
ADDITIONAL READING: Antifungal Drugs and Pregnancy
2000 Illinois Teratogen Information Service
Butorphanol
Analgesic; Partial Opiate Agonist
CATEGORY:C
BREAST FEEDING: Compatible [G3].
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Caffeine
Stimulant
CATEGORY:B
BREAST FEEDING:Compatible [G3].
NEONATAL SIDE EFFECTS:Irritability,
poor sleeping
CERCA LETTERATURA
ADDITIONAL READING: Caffeine and Pregnancy
1997 Illinois Teratogen Information Service
Calcitonin
Calcium Metabolism
CATEGORY: C
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Calcium
channel blockers
CATEGORY:C
BREAST FEEDING:Compatible
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
ADDITIONAL READING: Calcium Channel Blockers and Pregnancy
1996 Illinois Teratogen Information Service
Carbamazepine
Anticonvulsant
CATEGORY:D
The risk of neural tube defect is 1 to 2 % when used as monotherapy during first trimester. and
. Syndrome similar to hydantoin syndrome is also seen.
BREAST FEEDING:Excreted into human breast milk. Compatible [G3].
NEONATAL SIDE EFFECTS:Possible marrow suppression
CERCA LETTERATURA
1.Teratology. ACOG technical bulletin number 236--April 1997
Carbimazole
Antithyroid Agent
CATEGORY:D
BREAST FEEDING:With caution
NEONATAL SIDE EFFECTS:Goiter
CERCA LETTERATURA
Carisoprodo l
Skeletal Muscle Relaxant
CATEGORY: C
BREAST FEEDING:Concentrated into human milk. Avoid breast feeding.
NEONATAL SIDE EFFECTS: Sedation.
CERCA LETTERATURA
Cefprozil
Antibiotic, Cephalosporin
CATEGORY: B
BREAST FEEDING:Compatible [G3].
NEONATAL SIDE EFFECTS: Potential for diarrhea.
CERCA LETTERATURA
Cefuroxime
Antibiotic, Cephalosporin
CATEGORY: B
Crosses placenta.
1st trimester exposure in 143 fetuses
resulted in no increased rate of major or minor anomalies.
BREAST FEEDING:Excreted into milk. Compatible.
NEONATAL SIDE EFFECTS: Potential for diarrhea.
CERCA LETTERATURA
ADDITIONAL READING: Antibiotics and Pregnancy
1995 Illinois Teratogen Information Service
Celecoxib
Nonsteroidal Antiinflammatory, Cyclooxygenase-2 (COX-2) inhibitor
CATEGORY:C
BREAST FEEDING:It is not known whether this drug is excreted into human milk.
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Cephalexin
Antibiotic; Cephalosporin
CATEGORY:B
BREAST FEEDING:Compatible
NEONATAL SIDE EFFECTS:Diarrhea
CERCA LETTERATURA
ADDITIONAL READING: Antibiotics and Pregnancy
1995 Illinois Teratogen Information Service
Cephalosporins
CATEGORY:B
BREAST FEEDING:Compatible
NEONATAL SIDE EFFECTS:Diarrhea
CERCA LETTERATURA
ADDITIONAL READING: Antibiotics and Pregnancy
1995 Illinois Teratogen Information Service
Cetirizine
Cetirizine
CATEGORY:
B
Antihistamine. Metabolite of hydroxyzine. Molecular weight: 461.82.
"In mice, rats, and rabbits, cetirizine was not teratogenic at oral
doses up to 96, 225, and 135 mg/kg, respectively (approximately 40, 180 and 220
times the maximum recommended daily oral dose in adults on a mg/m 2 basis)"[1].
In a prospective, controlled, observational study of women exposed to either
hydroxyzine or cetirizine during pregnancy 39 women were exposed to cetirizine
during organogenesis. Most of the women had been treated with cetirizine for
rhinitis or urticaria. There were no significant differences found between the
cetirizine group and a control group in the rates of major or minor anomalies,
spontaneous abortions, stillbirths, mean birth weight, mode of delivery,
gestational age, or presence of neonatal distress [2].
In an observational study of newly marketed drugs prescribed in England
cetirizine was taken during the first trimester in 20 pregnancies. One patient
chose to have an elective abortion. There were 4 spontaneous abortions. The
remaining mothers delivered 16 normal infants (one set of twins) [3].
The American College of Obstetricians and Gynecologists (ACOG) and The American
College of Allergy, Asthma and Immunology (ACAAI) recommend chlorpheniramine and
tripelennamine as the antihistamines of choice for pregnant women. Cetirizine and loratadine may be considered (preferably after the first
trimester) in patients who cannot tolerate or do not respond to maximal doses of
topical therapy. [4]
BREAST FEEDING: Excreted into human milk. Not considered compatible with
breast feeding by the manufacturer [1].
SEARCH
LITERATURE
1. Physicians
Desk Reference 57th ed. Montvale, NJ: Thomson PDR; 2004: 2697
2.Einarson A, Bailey B, Jung G, Spizzirri D, Baillie M, Koren G. Prospective
controlled study of hydroxyzine and cetirizine in pregnancy. Ann Allergy Asthma
Immunol. 1997 Feb;78(2):183-6. MEDLINE
3. Wilton LV, Pearce GL, Martin RM, et al.: The outcomes of pregnancy in women
exposed to newly marketed drugs in general practice in England. Br J Obstet
Gynaecol 105:882- 889, 1998. MEDLINE
4. The use of newer asthma and allergy medications during pregnancy. Position
Statement. The American College of Obstetricians and Gynecologists (ACOG) and
The American College of Allergy, Asthma and Immunology (ACAAI). Ann Allergy
Asthma Immunol. 2000;84:475-480. MEDLINE
Chloramphenicol
Antibiotic
CATEGORY:C
BREAST FEEDING: The American Academy of Pediatrics has classified chloramphenicol as a drug "for which the effect on nursing infants is unknown but may be of concern" [G3].
NEONATAL SIDE EFFECTS:"Gray"disease, bone marrow suppression
CERCA LETTERATURA
Chlordiazepoxide
Sedative; Benzodiazepine
CATEGORY:D
Crosses placenta.
BREAST FEEDING:Contraindicated
NEONATAL SIDE EFFECTS: Neonatal withdrawal, hypotonicity.
CERCA LETTERATURA
Chloroquine
Antimalarial Agent
CATEGORY: Assigned to category C in past.
Pregnancy is not a contraindication to malaria prophylaxis with chloroquine or hydroxychloroquine[1].
BREAST FEEDING: Compatible [G3].
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
1.Recommendations for the Prevention of Malaria Among Travelers. MMWR 39(RR-3);1-10,1990
Chlorothiazide
Diuretic
CATEGORY:C
BREAST FEEDING: Compatible [G3].
NEONATAL SIDE EFFECTS:Thrombocytopenia
CERCA LETTERATURA
Chlorpheniramine
Antihistamine. Molecular weight: 274.8
CATEGORY:B
[1]
Results
of The Collaborative Perinatal Project found no increase in the incidence of
major malformations among 1070
pregnancies exposed during the first four lunar months to chlorpheniramine
[2].
Aselton P, et. al. also found no increase in the incidence of major
malformations among 175 pregnancies
exposed during the first trimester to chlorpheniramine [3].
Briggs et. al. reported that data from a surveillance study of Michigan
Medicaid recipients did not support an association between chlorpheniramine
and major malformations in 61 newborns who had been exposed to
chlorpheniramine during the first trimester [1].
A prospective controlled trial of 68 pregnancies that had been exposed to
chlorpheniramine at any time during pregnancy found no increase in the incidence
of major malformations. One child was born with congenital hip dysplasia [4].
The American College of Obstetricians and Gynecologists (ACOG) and The
American College of Allergy, Asthma and Immunology (ACAAI) recommended
chlorpheniramine and tripelennamine as the antihistamines of choice for use
during pregnancy [5].
SEARCH
LITERATURE
1. Briggs GG,Freeman RK, Yaffe SJ, Drugs in
Pregnancy and Lactation 6th edition,Baltimore, MD: Williams
& Wilkins,2002 p 246-7
2. Heinonen OP, et al: Birth Defects and Drugs in Pregnancy. Publishing Sciences
Group Inc., Littleton, MA, 1977.p 323-34.
3. Aselton P, et al.First-trimester drug use and congenital disorders. Obstet
Gynecol. 1985; 65: 451-5.MEDLINE
4. Diav-Citrin O, et al. Pregnancy outcome after gestational exposure to
loratadine or antihistamines: a prospective controlled cohort study.J Allergy
Clin Immunol. 2003; 111: 1239-43.MEDLINE
5. The use of newer asthma and allergy medications during pregnancy. Position
Statement. The American College of Obstetricians and Gynecologists (ACOG) and
The American College of Allergy, Asthma and Immunology (ACAAI). Ann Allergy
Asthma Immunol. 2000;84:475-480. MEDLINE
Chlorpromazine
Tranquilizer
CATEGORY: Assigned to category C in past.
Presently carries the following precautions: Safety for the use of chlorpromazine during pregnancy has not been established. Therefore, it is not recommended that the drug be given to pregnant patients except when, in the judgment of the physician, it is essential. The potential benefits should clearly outweigh possible hazards.
BREAST FEEDING: The American Academy of Pediatrics has classified chlorpromazine as a drug "for which the effect on nursing infants is unknown but may be of concern" [G3].
NEONATAL SIDE EFFECTS: There are reported instances of prolonged jaundice, extrapyramidal signs, hyperreflexia or hyporeflexia in newborn infants whose mothers received phenothiazines prenatally.
CERCA LETTERATURA
ADDITIONAL READING: The Treatment of Nausea and Vomiting in Pregnancy
2001 Illinois Teratogen Information Service
Chlorpropamide
Antidiabetic Agent, Sulfonylurea
CATEGORY:C
Crosses placenta.
BREAST FEEDING:Excreted into breast milk.
NEONATAL SIDE EFFECTS:Hypoglycemia
CERCA LETTERATURA
Cholestyramine
Antilipemic Agent; Resin
CATEGORY:C
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Cimetidine
Treatment of Peptic Ulcer
CATEGORY:B
BREAST FEEDING: Compatible. Concentrated in human milk [G3].
NEONATAL SIDE EFFECTS:None reported.
ADDITIONAL READING: Gastroesophogeal Reflux (GERD) Medications in Pregnancy
1999 Illinois Teratogen Information Service
CERCA LETTERATURA
Ciprofloxacin
Antiinfective; Quinolone
CATEGORY:C
Crosses placenta. 1st trimester exposure in 105 fetuses resulted in no increased rate of major or minor anomalies. Achievement of developmental milestones and musculoskeletal system development were normal.
However, the authors of the study cautioned that longer follow-up and magnetic resonance imaging of the joints may be warranted to exclude subtle cartilage and bone damage.[1]
BREAST FEEDING: Compatible [G3].
NEONATAL SIDE EFFECTS: None reported.
CERCA LETTERATURA
1. Loebstein R et al.Pregnancy Outcome Following Gestational Exposure to Fluoroquinolones: a Multicenter Prospective Controlled StudyAntimicrob. Agents Chemother. 1998. 42:1336-1339.
Cisapride
Removed from U.S. market 2000.
Treatment of Gastroesophageal Reflux Disease; GI Stimulant.
CATEGORY: C
A prospective multicenter study of 129 pregnant women exposed to cisapride at any time during pregnancy, including 88 infants exposed during organogenesis,
found no increase in major or minor anomalies, or rates of miscarriage.
[1]
BREAST FEEDING:Excreted into human milk in low concentration. Compatible [G3].
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
1.Bailey B, Addis A, Lee A, Sanghvi K, Mastroiacovo P, Mazzone T, Bonati M, Paolini C, Garbis H, Val T, De Souza CF, Matsui D, Schechtman AS, Conover B, Lau M, Koren G.
Cisapride use during human pregnancy: a prospective, controlled multicenter study.
Dig Dis Sci. 1997 Sep;42(9):1848-52.MEDLINE
ADDITIONAL READING: Gastroesophogeal Reflux (GERD) Medications in Pregnancy
1999 Illinois Teratogen Information Service
Cisplatin
Antineoplastic
CATEGORY:D
BREAST FEEDING: Excreted into human breast milk [1,2]. The American Academy of Pediatrics has classified cisplatin as a drug "usually compatible with breastfeeding" [G3]. The WHO Working Group on Human Lactation does not recommend nursing during cisplatin chemotherapy [G8].
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
1. de Vries EG, van der Zee AG, Uges DR, Sleijfer DT. Excretion of platinum into breast milk. Lancet 1:497, 1989.
MEDLINE
2. Ben-Baruch G, Menczer J, Goshen R, Kaufman B, Gorodetsky R. Cisplatin excretion in human milk. J Natl Cancer Inst 84: 451-2, 1992.
MEDLINE
ADDITIONAL READING: Cancer, Chemotherapy and Pregnancy
1998 Illinois Teratogen Information Service Chemotherapy in Pregnancy
Motherisk
Citalopram
Antidepressant. Selective serotonin reuptake inhibitor (SSRI) . Molecular weight:
405.35.
CATEGORY:
C
Citalopram is metabolized primarily to demethylcitalopram (DCT) which is
approximately one eighth as potent in the inhibition of serotonin reuptake
as citalopram [1]
In reproductive animal studies, citalopram has been shown to have adverse
effects on embryo/fetal and postnatal development when administered at doses
greater than human therapeutic doses. Decreased embryo/fetal growth and survival
and an increased incidence of fetal abnormalities (including cardiovascular and
skeletal defects) were observed in the rat at a maternally toxic dose (18 times
the maximum recommended human dose (MRHD) of 60 mg/day on a body surface area
(mg/m 2 ) basis). In a rabbit study, no adverse effects on embryo/fetal
development were observed at doses of up to approximately 5 times the MRHD [1].
In an isolated perfused human placenta model the mean transplacental transfer
for citalopram and desmethylcitalopram was found to be 9.1% and 5.6%
respectively. The presence of albumin was necessary for the transplacental
transfer of citalopram [2].
Ericson and co-workers prospectively identified 365 women enrolled in The
Swedish Medical Birth Registry who used citalopram during early pregnancy.
Exposure to citalopram did not appear to increase the rate of major
malformations above the expected baseline rate [3].
BREAST FEEDING: Citalopram is excreted into breast milk. The milk/serum
concentration ratio is 1.16 to 3 [4-6].
Heikkinen T, et. al., prospectively compared eleven breast-feeding women
taking citalopram 20 mg to 40 mg once daily with a matched control group of 10
women who were not taking medication. Infant citalopram and metabolite
plasma concentrations were found to be very low or undetectable. The
neurodevelopment of all infants up to the age of 1 year was normal [6]
Rampono J, et. al., as with the previous study, found very low or
absent plasma concentrations of citalopram and demethylcitalopram in breast fed
infants of 7 mothers taking citalopram for the treatment of depression.
They estimated the mean combined dose of citalopram and demethylcitalopram
transmitted to infants via breast milk to be 4.4-5.1% as citalopram equivalents[7].
This is below the 10% notional level of concern.
Nonetheless, Nordeng and coworkers suggest that high doses of citalopram be
used with caution in breastfeeding women [8].
NEONATAL SIDE EFFECTS: Neonatal withdrawal syndrome may occur after
third trimester in utero SSRI exposure. Irritability, constant crying, shivering,
increased tonus, eating ,sleeping difficulties, and convulsions have been
reported [9].
"Uneasy sleep" has been reported in the breast fed infant of one
mother taking 40 mg/day of citalopram [10]. The usual dose of citalopram is 20
to 40 mg/day [1].
SEARCH
LITERATURE
REFERENCES
1. Physicians Desk Reference 57th ed. Montvale, NJ: Thomson PDR; 2003:1344-1345.
2.Heikkine T, et al., Transplacental transfer of citalopram, fluoxetine and
their primary demethylated metabolites in isolated perfused human placenta.BJOG.
2002;109:1003-8.MEDLINE
3. Ericson A, et. al.: Delivery outcome after the use of antidepressants in
early pregnancy. Eur J Clin Pharmacol 55:503-508, 1999. MEDLINE
4. Spigset O, Cet al . Excretion of citalopram in breast milk. Br J Clin
Pharmacol 1997;44:295-8. MEDLINE
5. Jensen PN, et al.: Citalopram and desmethylcitalopram concentrations in
breast milk and in serum of mother and infant. Ther Drug Monit 1997;19:236- 9.MEDLINE
6. Heikkinen T, et al., Citalopram in pregnancy and lactation. Clin Pharmacol
Ther. 2002;72:184-91. MEDLINE
7. Rampono J, et al.: Citalopram and demethylcitalopram in human milk;
distribution, excretion andeffects in breast fed infants. Br J Clin Pharmacol
2000; 50:263-8. MEDLINE
8. Nordeng H, et al., [The transfer of selective serotonin reuptake inhibitors
to human milk] Tidsskr Nor Laegeforen. 2001;121:199-203. MEDLINE
9. Nordeng H, et al Neonatal withdrawal syndrome after in utero exposure to
selective serotonin reuptake inhibitors. Acta Paediatr. 2001;90:288-91.MEDLINE
10. Schmidt K, et al., Citalopram and breast-feeding: serum concentration and
side effects in the infant. Biol Psychiatry. 2000;47:164-5. MEDLINE
Clarithromycin
Anti-infective; Macrolide
CATEGORY:C
In prospective controlled study Einarson et al. found no increase in major or minor fetal anomalies in the infants of 157 women exposed to clarithromycin at any time during pregnancy including 122 infants exposed during the 1st trimester.
However, the frequency of spontaneous abortions in the exposed group was higher (14%) than in the control group (7%) (p = 0.04) [1].
BREAST FEEDING:Excreted into human breast milk [2].
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
1.Einarson A, Phillips E, Mawji F, D'Alimonte D, Schick B, Addis A, Mastroiacova P, Mazzone T, Matsui D, Koren G.
A prospective controlled multicentre study of clarithromycin in pregnancy.
Am J Perinatol. 1998;15(9):523-5.MEDLINE
2. Sedlmayr T, Peters F, Raasch W, Kees F.[Clarithromycin, a new macrolide antibiotic. Effectiveness in puerperal infections and pharmacokinetics in breast milk]
Geburtshilfe Frauenheilkd. 1993 Jul;53(7):488-91. German.MEDLINE
3. Drinkard CR, Shatin D, Clouse J.Postmarketing surveillance of medications and pregnancy outcomes: clarithromycin and birth malformations.
Pharmacoepidemiol Drug Saf. 2000;9:549-56.MEDLINE
Clindamycin
Antibiotic, Semisynthetic
CATEGORY:B
BREAST FEEDING: Compatible [G3].
NEONATAL SIDE EFFECTS:One case of
GI bleeding
CERCA LETTERATURA
Clofibrate
Anilipemic Agent
CATEGORY:C
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Clomiphene
Nonsteroidal Ovulatory Stimulant
CATEGORY:X
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
ADDITIONAL READING: Clomiphene Citrate (Clomid) and Pregnancy
1996 Illinois Teratogen Information Service
Clonazepam
Anticonvulsant; Benzodiazepine
CATEGORY: D
BREAST FEEDING: Contraindicated
NEONATAL SIDE EFFECTS: Neonatal flaccidity, respiratory and feeding difficulties, and hypothermia in children born to mothers who have been receiving benzodiazepines late in pregnancy. Risk of withdrawal symptoms during the postnatal period.
CERCA LETTERATURA
ADDITIONAL READING: Update:Benzodiazepines in Pregnancy
1999 Illinois Teratogen Information Service
Clonidine
Antihypertensive Agent,Alpha-agonist
CATEGORY:C
Crosses placenta.
BREAST FEEDING: Excreted into milk in high concentration. In a clinical study involving nine nursing mothers clonidine concentrations in the serum of the breast-fed newborns were about half those of the mothers. No adverse effects were observed in any of the infants [1]. The manufacturer recommends caution should be exercised when clonidine is administered to a nursing woman.
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
1.Hartikainen-Sorri AL, Heikkinen JE, Koivisto M. Pharmacokinetics of clonidine during pregnancy and nursing.
Obstet Gynecol. 1987 Apr;69(4):598-600.
MEDLINE
Clopidogrel
Oral Antithrombic Agent,Platelet Inhibitor
CATEGORY: B
BREAST FEEDING:It is not known whether this drug is excreted in human milk.
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Clotrimazole
Topical Antifungal
CATEGORY:B
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Cloxacillin
Antibiotic, Penicillins
CATEGORY:B
BREAST FEEDING:Compatible
NEONATAL SIDE EFFECTS:Diarrhea
CERCA LETTERATURA
Cocaine
CATEGORY:C
CATEGORY: X as illicit drug.
Placental abruption, cerebral infarcts
,necrotizing enterocolitis.
BREAST FEEDING:Contraindicated
NEONATAL SIDE EFFECTS:Seizure,apnea
CERCA LETTERATURA
ADDITIONAL READING: Cocaine
1999 Organization of Teratology Information Services
Codeine
Opiate Agonist
CATEGORY:C
BREAST FEEDING: Compatible [G3].
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Colchicine
Treatment of gout
CATEGORY:D
BREAST FEEDING: Compatible [G3].
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Contraceptives,oral
CATEGORY:X
BREAST FEEDING: Compatible [G3].
NEONATAL SIDE EFFECTS:Breast enlargement,
proliferation of vaginal epithelium,decreased milk production
CERCA LETTERATURA
Cyclizine
Antiemetic, Antihistamine. Chemically similar to
meclizine
CATEGORY:B
1st trimester exposure to cyclizine in 111 pregnancies resulted in no increase in the rate of major or minor fetal anomalies [G1].
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
ADDITIONAL READING: The Treatment of Nausea and Vomiting in Pregnancy
2001 Illinois Teratogen Information Service
Cyclobenzaprine
Tricyclic muscle relaxant
CATEGORY: B
1st trimester exposure in 542 fetuses
resulted in no increased rate of major or minor anomalies [G1].
BREAST FEEDING:It is not known whether this drug is excreted in human milk.
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Cyclophosphamide
Antineoplastic Agent
CATEGORY:D
BREAST FEEDING: The American Academy of Pediatrics classified cyclophosphamide as contraindicated during breastfeeding in 1994[G9].
, and listed it as a cytotoxic drug " that may interfere with cellular metabolism of the nursing infant" in 2001[G3].
NEONATAL SIDE EFFECTS:Possible immune suppression[1]
CERCA LETTERATURA
1. Amato D, Niblett JS. Neutropenia from cyclophosphamide in breast milk. Med J Aust. 1977;1:383-384
ADDITIONAL READING: Cancer, Chemotherapy and Pregnancy
1998 Illinois Teratogen Information Service Chemotherapy in Pregnancy
Motherisk
Cyclosporine
Antineoplastic Agent
CATEGORY:C
Possible increase in low birth weight and increased rate of preterm birth.
BREAST FEEDING: Cyclosporine is excreted into human milk. However, blood levels of cyclosporine in 7 infants breastfed by cyclosporine-treated mothers were below the detection limit of the drug assay.
The American Academy of Pediatrics has classified cyclosporine as a cytotoxic drug " that may interfere with cellular metabolism of the nursing infant"[G3].
NEONATAL SIDE EFFECTS: Possible immune suppression
CERCA LETTERATURA
1. Nyberg G, Haljamae, Frisenette-Fich C, Wennergren M, Kjellmer I. Breast-feeding during treatment with cyclosporine. Transplantation. 1998;65:253-255 MEDLINE
Cyproheptadine
Antihistamine, Antiserotonergic Agent
CATEGORY:B
BREAST FEEDING:Compatible
NEONATAL SIDE EFFECTS:Agitation, poor sleep and feeding pattern
CERCA LETTERATURA
Desipramine
CATEGORY: Previously assigned to category C.
Presently carries the following precautions: Safe use of desipramine hydrochloride during pregnancy and lactation has not been established; therefore, if it is to be given to pregnant patients, nursing mothers, or women of childbearing potential, the possible benefits must be weighed against the possible hazards to mother and child. Animal reproductive studies have been inconclusive.
BREAST FEEDING: The American Academy of Pediatrics has classified desipramine as a drug "for which the effect on nursing infants is unknown but may be of concern" [G3].
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Desmopressin
CATEGORY:B
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Dexamethasone
CATEGORY:C
BREAST FEEDING:
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
ADDITIONAL READING: Corticosteroids in Pregnancy
2000 Illinois Teratogen Information Service
Dexfenfluramine
Anti-Obesity Agent
CATEGORY:C
BREAST FEEDING:Not recommended
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Dextroamphetamine
CATEGORY:D
BREAST FEEDING:Contraindicated
NEONATAL SIDE EFFECTS:CNS stimulation
CERCA LETTERATURA
Dextromethorphan
Antitussive . D-isomer of the codeine analog levorphanol. N-methyl-D-aspartate
(NMDA) receptor antagonist. Molecular weight: 370.33
CATEGORY:C
[1]
In developmental studies involving chick embryos dextromethorphan at 500 nmol/embryo/d
killed more than half the embryos and induced congenital defects in about
one-eighth of the survivors; dextromethorphan was also highly lethal at 50 nmol/embryo/d
[2]. However, the validity of chick embryos as good model for predicting
teratogenic potential in humans has been questioned by several investigators
[3,4].
Retrospective data from the Collaborative Perinatal Project showed no
increased rate of major or minor anomalies after exposure to dextromethorphan
during the first four months of pregnancy in 300 women [5]. In addition cohort
studies involving 187 women exposed to dextromethorphan
during the first trimester did not demonstrate an increase in the rate of
major malformations above the expected baseline rate [6,7]. Epidemiologic
data from the Spanish Collaborative Study of Congenital Malformations also did
not support an association between the use of dextromethorphan during pregnancy
and an increased risk of congenital defects [8].
Blockade of N-methyl-D-aspartate (NMDA)
glutamate receptors for only a few hours during late fetal or early
neonatal life triggered widespread apoptotic neurodegeneration in the
developing rat brain in a study by Ikonomidou C, et al [9]. Debus O
and coworkers have urged caution in the use of dextromethorphan during pregnancy
until long term neurodevelopmental studies have been conducted on the offspring
of mothers who received dextromethorphan during their pregnancies
[10].
BREAST FEEDING: It is not known whether dextromethorphan or its
metabolites are excreted in human breast milk.
SEARCH
LITERATURE
1. Briggs GG,Freeman RK, Yaffe SJ, Drugs in
Pregnancy and Lactation 6th edition,Baltimore, MD: Williams
& Wilkins,2002 p 384
2. Andaloro VJ, et al Dextromethorphan and other N-methyl-D-aspartate receptor
antagonists are teratogenic in the avian embryo model.Pediatr Res. 1998;43:1-7.MEDLINE
3.Brent RL. The teratogenicity of N-methyl-D-aspartate (NMDA) receptor
antagonists.Pediatr Res. 1998; 44: 415-7. PMID: MEDLINE
4. Brent RL. et al. Response to Dr. Rosenquist's comments pertaining to the
paper by Andaloro et al. ('98) "Dextromethorphan and other
N-methyl-D-aspartate receptor antagonists are teratogenic in the avian embryo
model" and letters to the editor by Polifka JE and Shepard TH ('98) and
Brent RL ('98)Teratology. 1999 ; 60: 61-2.MEDLINE
5.Heinonen OP et al: Birth Defects and Drugs in Pregnancy, Littleton, Publishing
Sciences Group, 1977. p 378-383
6. Aselton P, Jick H, Milunsky A et al: First-trimester drug use and congenital
disorders. Obstet Gynecol 65:451-5, 1985. 451-5.MEDLINE
7.Einarson A, Lyszkiewicz D, Koren G.The safety of dextromethorphan in pregnancy
: results of a controlled study. Chest. 2001;119:466-9. MEDLINE
8. Martinez-Frias ML, Rodriguez-Pinilla E.Epidemiologic analysis of prenatal
exposure to cough medicines containing dextromethorphan: no evidence of human
teratogenicity.Teratology. 2001;63:38-41. MEDLINE
9.Ikonomidou C, et al. Blockade of NMDA receptors and apoptotic
neurodegeneration in the developing brain.Science. 1999;283:70-4.MEDLINE
10. Debus O, et al. Dextromethorphan in pregnancy.[Letter] Chest.
2001;120:1038-40. MEDLINE
ADDITIONAL READING: Over
the Counter Cold Medications in Pregnancy
1998 Illinois Teratogen Information Service
Diazepam
CATEGORY:D
BREAST FEEDING: The American Academy of Pediatrics has classified diazepam as a drug "for which the effect on nursing infants is unknown but may be of concern" [G3].
NEONATAL SIDE EFFECTS:Sedation
CERCA LETTERATURA
ADDITIONAL READING: Update:Benzodiazepines in Pregnancy
1999 Illinois Teratogen Information Service
Diazoxide
CATEGORY:C
BREAST FEEDING:Contraindicated
NEONATAL SIDE EFFECTS:Hyperglycemia
CERCA LETTERATURA
Dicumarol
CATEGORY:D
BREAST FEEDING:As for warfarin
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Digoxin
Antiarrhythmic, miscellaneous
CATEGORY:C
BREAST FEEDING:Compatible [G3].
NEONATAL SIDE EFFECTS:GI upset,diarrhea,heart
rate changes
CERCA LETTERATURA
Diltiazem
Calcium channel blocker
27 first trimester exposures during first trimester showed an increase rate of cardiovascular defects. Suggestive of an association.
CATEGORY: C
BREAST FEEDING: Compatible [G3].
NEONATAL SIDE EFFECTS: Potential for hypotension.
CERCA LETTERATURA
ADDITIONAL READING: Calcium Channel Blockers and Pregnancy
1996 Illinois Teratogen Information Service
Diphenhydramine
Diphenhydramine
Antihistamine. Molecular weight:255.36
CATEGORY:
B
Diphenhydramine may cause uterine irritability or contractions near term when
used in high doses (greater than 50mg) [1,2]
In 1974 Saxen reported that a study group of 599 infants with oral clefting
were more likely to have been exposed to diphenhydramine during the first
trimester than a control group of infants without clefting [3]. Subsequent
retrospective studies of more than 2300 infants have found no association
between first trimester exposure to diphenhydramine and oral clefting or major
malformations [4-6]
Stillbirth has been reported following the use of diphenhydramine and
temazepam during human pregnancy. The toxicity of this combination was confirmed
in pregnant rabbits [7].
BREAST FEEDING: The manufacturer considers diphenhydramine to be
contraindicated during breast feeding.
NEONATAL SIDE EFFECTS: Potential for severe sedation if administered to the
mother before delivery [8].
SEARCH
LITERATURE
1. Hara GS et al. J Kans Med Soc. 1980;81:134-6,155. MEDLINE
2. Brost BC, Diphenhydramine overdose during pregnancy: lessons from the past.
Am J Obstet Gynecol. 1996;175:1376-7. MEDLINE
3. Saxen I: Cleft palate and maternal diphenhydramine intake. [Letter] Lancet.
1974;1:407-8. MEDLINE
4. Heinonen OP et al.: Birth Defects and Drugs in Pregnancy, Littleton
Publishing Sciences Group, 1977, pp 322-7.
5. Aselton P et al. First-trimester drug use and congenital disorders. Obstet
Gynecol.1985;65:451-5. MEDLINE
6. Briggs GG,Freeman RK, Yaffe SJ, Drugs in Pregnancy and Lactation 6th edition,Baltimore,
MD: Williams
& Wilkins,2002 p 426.
7. Kargas GA, Perinatal mortality due to interaction of diphenhydramine and
temazepam. [Letter] N Engl J Med. 1985;313:1417-8. MEDLINE
8. Miller AA Diphenhydramine toxicity in a newborn: a case report. J Perinatol.
2000;20:390-1. MEDLINE
Dipyridamole
CATEGORY:C
BREAST FEEDING:Compatible
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
Disopyramide
CATEGORY:C
BREAST FEEDING: Compatible [G3].
NEONATAL SIDE EFFECTS:
CERCA LETTERATURA
GENERAL REFERENCES
G1.Briggs GG,Freeman RK, Yaffe SJ, Drugs in Pregnancy
and Lactation 5th edition,Baltimore, MD: Williams & Wilkins,1998
G2. Cunningham GF, MacDonald PC et al (eds);Williams Obstetrics,20th
ed,Stamford ,CT:.Appleton and Lange, 1997
G3. Transfer of drugs and other chemicals into human milk. Pediatrics. 2001 Sep;108(3):776-89. Review.
G4 .Shepard TH. Catalog of Teratogenic Agents. 9th ed.Baltimore,
MD: Johns Hopkins University Press, 1998
G5. Gleicher Norbert ed. Principles & Practice of
Medical Therapy in Pregnancy. 3rd ed. Stamford, CT: Appleton & Lange,
1998
G6. Physicians' Desk Reference. 54th ed. Montvale, NJ: Medical Economics Company,2000
G7. Centers for Disease Control & Prevention. General Recommendations on Immunization:
Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 43 (No.
RR-1): 20-21, 1994.
G8. The WHO Working Group, Bennet PN (ed).: Drugs and Human Lactation. Elsevier, Amsterdam, New York, Oxford, 1988.
G9.Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human breast milk. Pediatrics 93:137-150, 1994.
G10.Heinonen OP, Slone D, Shapiro S: Birth defects and drugs in pregnancy. Littleton:Publishing Sciences Group, 1977
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