Microsoft word - pregnancy breastfeeding - safe use of anti-infective agents oct 14 post-mr.doc
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIBACTERIAL AGENTS Name of Agent / Class Pregnancy Breastfeeding Aminoglycosides Amikacin
• Not expected to increase risk of major congenital
• Considered safe during breastfeeding
• Monitor nursing infant for GI symptoms.
• Monitor drug concentrations for efficacy as higher
• Theoretical risk of ototoxicity and nephrotoxicity.
Penicillins Ampicillin
• Not expected to increase risk of major congenital
• Considered safe during breastfeeding
• Monitor nursing infant for GI symptoms.
• Amoxicillin/clavulinic acid should be avoided in
women at risk of preterm delivery due to increased
risk of neonatal necrotising enterocolitis.
1. Human data on cloxacillin, piperacillin/tazobactam,
and ticarcillin are limited; however, penicillins as a class are considered safe during pregnancy.
Cephalosporins Cefazolin
• Not expected to increase risk of major congenital
• Considered safe during breastfeeding
• Monitor nursing infant for GI symptoms.
The information in this table was prepared by Motherisk and is to be used for guidance purposes only. For more information, please contact the Motherisk hotline Monday to Friday 9 AM to 5 PM. Phone 416-813-6780. Fax 416-813-7562. Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIBACTERIAL AGENTS Name of Agent / Class Pregnancy Breastfeeding Carbapenems Ertapenem
• No human data; however, there is no evidence of
increased risk of major congenital malformations
cause adverse effects in breastfed infants
• Use when benefit outweighs unknown risk to the
• Monitor nursing infant for GI symptoms.
Macrolides Azithromycin
• Not expected to increase risk of major congenital
• Not expected to cause adverse effects in
• Monitor nursing infant for GI symptoms.
• Not expected to cause adverse effects in
• Not expected to increase risk of major congenital
• Monitor nursing infant for GI symptoms.
• Not expected to increase risk of major congenital
• Not expected to cause adverse effects in
• Monitor nursing infant for GI symptoms.
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIBACTERIAL AGENTS Name of Agent / Class Pregnancy Breastfeeding Quinolones Ciprofloxacin
• Not expected to increase risk of major congenital
• Monitor nursing infant for GI symptoms.
• Limited human data; however, short-term
• Not expected to increase risk of major congenital
• Monitor nursing infant for GI symptoms.
* It would be preferable to use of a drug other than moxifloxacin for which safety information is available.
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIBACTERIAL AGENTS Name of Agent / Class Pregnancy Breastfeeding Sulfonamides Co-trimoxazole
• Case control studies suggest an association with
• Trimethoprim is present at low levels in
neural tube defects (NTDs), cardiovascular
breast milk and is not expected to cause
malformations and facial clefting as a result of
• During 1st trimester, use of an alternate agent
• If use during the 1st trimester cannot be avoided,
high dose folic acid (4-5mg/day) should be given to
• Sulfamethoxazole should be used with
• Sulfamethoxazole should be avoided near term
due to potential toxicity to the newborn (hemolytic
while breastfeeding an infant with G6PD deficiency.
• Monitor nursing infant for GI symptoms.
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIBACTERIAL AGENTS Name of Agent / Class Pregnancy Breastfeeding Tetracyclines Doxycycline
• Should be avoided after 15 weeks of gestation due • Low levels in breast milk and reduced oral
to reports of possible discoloration of the deciduous
• Short-term use is not expected to cause
• Prolonged or repeated treatment courses
during nursing should be avoided (theoretical precaution).
• Monitor nursing infant for GI symptoms. • Black discoloration of breast milk has
Miscellaneous Antibacterial Agents Clindamycin
• Not expected to increase risk of major congenital
diarrhea, oral thrush, and for blood in the
stool suggestive of antibiotic-associated colitis (rare).
• No human data on exposure during 1st trimester.
• Animal studies show no evidence of fetal risk.
• Should be used only when benefit outweighs
• Not expected to cause adverse effects in
• Monitor nursing infant for GI symptoms.
• An alternate agent with a known safety profile
• An alternate agent with a known safety
• Should be used only when benefit outweighs
• Monitor nursing infant for GI symptoms.
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIBACTERIAL AGENTS Name of Agent / Class Pregnancy Breastfeeding
• Not expected to increase risk of major congenital
• Not expected to cause adverse effects in
• The theoretical risk suggested by in vitro and
• Infant dose via breast milk is lower than
animal studies has not been observed in clinical
breastfeeding (pump and discard milk) for 12 to 24 hours after single-dose (e.g., 2 g) maternal treatment of Trichomonas infection.
• Monitor nursing infant for GI symptoms.
• Not expected to increase risk of major congenital
• There is a theoretical risk of hemolytic anemia in
newborns, particularly in those with G6PD
• Not expected to cause adverse effects in
deficiency, who are exposed in utero to
nitrofurantoin close to delivery. If there is a
• Monitor nursing infant for GI symptoms.
concern, an alternate agent should be used after 37 weeks of gestation.
• Not expected to increase risk of major congenital
• Limited information; however, amounts in
• Prenatal exposure to rifampin has been linked to
• Breastfeeding should not be discouraged
hemorrhagic disease of the newborn. Prophylactic
administration of vitamin K is recommended to
• Monitor nursing infant for GI symptoms.
• No reports on use during human pregnancy.
• Tigecycline is structurally related to tetracycline
and thus should be avoided after 15 weeks of
• Use of an alternate agent with a known
• Use of an alternate agent with a known safety
• Monitor nursing infant for GI symptoms.
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIBACTERIAL AGENTS Name of Agent / Class Pregnancy Breastfeeding
• Limited information; however, amounts in
• Should be used only when benefit outweighs
breast milk and oral bioavailability are low.
• Monitor nursing infant for GI symptoms.
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIFUNGAL AGENTS Name of Agent / Class Pregnancy Breastfeeding
• Not expected to increase risk of major congenital
• Should be used only when benefit outweighs
• Not expected to cause adverse effects in
• Should be avoided in 1st trimester, whenever
• Not expected to cause adverse effects in
• Monitor breastfed infant for symptoms of
• Monitor breastfed infant for GI symptoms.
• Not expected to increase risk of major congenital
• Amounts found in breast milk are lower
malformations when used in low-doses (150 mg)
• Considered safe during breastfeeding
• There are case reports of congenital anomalies
with prolonged use in doses > 400 mg/day during
the 1st trimester. (Causation has not been proven).
• Not expected to increase risk of major congenital
• Use of an alternate agent with a known
• Can be considered when other agents have failed
and the benefit outweighs the unknown risk to the fetus.
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIFUNGAL AGENTS Name of Agent / Class Pregnancy Breastfeeding
• Should be used only when benefit outweighs
• Animal studies have suggested voriconazole is
• Should be avoided during pregnancy at least for
the 1st trimester unless other treatments have failed and the benefit outweighs the unknown risk to the fetus.
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIVIRAL AGENTS Name of Agent / Class Pregnancy Breastfeeding
• Not expected to increase risk of major congenital
• Considered safe during breastfeeding.
• Amounts found in breast milk are lower
• Case reports of congenital malformation with
• Use of an alternate antiviral agent with a
• Use of an alternate antiviral agent with a known
safety profile would be preferred when possible.
• Not expected to increase risk of major congenital
malformations, based on a small number of
• Use of an alternate antiviral agent with a
known safety profile would be preferred when possible.
• Case reports describe treatment in 2nd and 3rd
• Should be avoided during breastfeeding.
trimester with no adverse effects in the neonates.
• Should be used only when the benefit outweighs
• Due to potential for renal toxicity, close follow up of
the fetus and monitoring of amniotic fluid volume are recommended.
• Should be used only when the benefit outweighs
• Not expected to increase risk of major congenital
• Not expected to cause adverse effects in
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIMALARIAL AGENTS Name of Agent / Class Pregnancy Breastfeeding
• Limited human data, mostly on use in 2nd and 3rd
• Should be used only when the benefit outweighs
transferred in breast milk is insufficient to
provide adequate protection against malaria for the infant.
• Limited human data, mostly on use in 2nd and 3rd
• Not expected to cause adverse effects in
• May be used to treat uncomplicated chloroquine-
resistant P. falciparum infection if:
o Other options are not available or not suitable
transferred in breast milk is insufficient to
o The benefit of its use outweighs the unknown
• Plasma concentrations of atovaquone and
proguanil were found in one study to be lower in pregnant women due to an increase in clearance and volume of distribution. It should be noted that all women in this study were cured of their initial infection in 1-3 days. Thus, the clinical significance of those pharmacokinetic changes is unclear.
• Not expected to increase risk of major congenital
• Not expected to cause adverse effects in
transferred in breast milk is insufficient to provide adequate protection against malaria for the infant.
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIMALARIAL AGENTS Name of Agent / Class Pregnancy Breastfeeding
• Not expected to increase risk of major congenital
malformations above the baseline risk in general
diarrhea, oral thrush, and for blood in the
stool suggestive of antibiotic-associated
• Recommended for treatment of uncomplicated
chloroquine-resistant P. falciparum infection.
transferred in breast milk is insufficient to provide adequate protection against malaria for the infant.
• Should be avoided after 4-5 months of gestation,
• Low levels in breast milk and low oral
due to reports of possible discoloration of the
• Short-term use is not expected to cause
• Prolonged or repeated treatment courses
during nursing should be avoided (theoretical precaution).
• Monitor nursing infant for GI symptoms. • The quantity of antimalarial drugs
transferred in breast milk is insufficient to provide adequate protection against malaria for the infant.
• Should be used only when the benefit of its use
• Not expected to cause adverse effects
outweighs the unknown risk to the fetus.
• Prophylactic administration of this drug should be
• There is a theoretical risk of hemolytic anemia in a
transferred in breast milk is insufficient to
provide adequate protection against malaria for the infant.
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents ANTIMALARIAL AGENTS Name of Agent / Class Pregnancy Breastfeeding
• Not expected to increase risk of major congenital
• Not expected to cause adverse effects
malformations when used in therapeutic doses.
• Recommended for treatment of uncomplicated
chloroquine-resistant infection caused by
P. falciparum and P. vivax.
transferred in breast milk is insufficient to provide adequate protection against malaria for the infant.
Pregnancy & Breastfeeding – Safe Use of Anti‐infective Agents Appendix A Dosage Adjustment in Pregnancy – General Considerations
Some of the physiological changes occurring in pregnancy may affect the pharmacokinetics of drugs taken during the gestational period and postpartum. Depending on the clinical significance of these changes, adjustment of the dose and/or dosing interval may warrant consideration. Below are some examples of altered drug distribution and elimination in pregnancy. • Increased maternal plasma volume may increase the volume of distribution of some drugs, which may require a dose increase. • Decreased plasma protein concentration, specifically albumin, may increase the free fraction of highly protein bound drugs, which
• Increased renal blood flow and glomerular filtration rate may increase the elimination of drugs that are excreted primarily in the
urine. This may require use of an increased dose and/or a shorter dosing interval.
• Alterations in the activity of hepatic drug metabolizing enzymes may require dosage adjustment as follows.
o Decreased activity (e.g., CYP1A2 and CYP2C19). For drugs that are dependent on these enzymes for elimination, a dose
reduction may be required. For drugs that require these enzymes for conversion to their active form, a dose increase may be appropriate.
o Increased activity (e.g., CYP3A, CYP2D6 and CYP2C9). For drugs that are dependent on these enzymes for elimination,
a dose increase may be required. For drugs that require these enzymes for conversion to their active form, a dose reduction may be required.
Note: there is a lack of pharmacokinetic data on which to base dosage adjustment of anti-infective agents in pregnancy, and there is a lack of evidence demonstrating benefit. Accordingly, routine dosage adjustment is not practiced at SHSC.
Genetic Analysis: Biomolecular EngineeringViability of E . coli cells containing phage RNA polymerase andpromoter: interference of plasmid replication by transcriptionYoung-Soo Kwon, Jinsuk Kim, Changwon Kang * Department of Biological Sciences , Korea Ad 6 anced Institute of Science and Technology , Taejon 305-701, South Korea Received 2 January 1998; received in revised form 8 Ju