AU: Tetracyclines are considered safe for use during the first 18 weeks of pregnancy (16 weeks postconception); use should be avoided during the second and third trimesters of pregnancy.
UK: Use of most oral formulations is contraindicated; use of the 40 mg capsule formulation is contraindicated during the second and third trimesters.
US: Use of the IV formulation is not recommended unless considered essential for patient welfare. Most oral formulations of this drug should not be used during pregnancy unless the benefit outweighs the risk; use of the 40 mg capsule formulation is not recommended.

AU TGA pregnancy category: D
US FDA pregnancy category:
-Most products: D
-Doryx(R) MPC, Vibramycin(R), Vibra-Tabs(R): Not assigned.

Risk summary: Use of this drug in pregnant women may cause fetal harm.

Comments:
-Use of tetracyclines after the first 18 weeks of pregnancy may affect the formation of the baby's teeth and cause discoloration.
-According to some authorities, this drug should be used during tooth development (e.g., last half of pregnancy) only if benefits are expected to outweigh risks in severe or life-threatening conditions (e.g., anthrax, Rocky Mountain spotted fever), especially if alternative therapies are unavailable.
-If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus.
-According to some authorities, the 40 mg capsule formulation should be stopped at once if the patient becomes pregnant.

Animal studies have revealed evidence of embryofetal toxicity, including toxic effects on skeletal formation. Animal studies indicate this drug crosses the placenta and is found in fetal tissues. There are no controlled data in human pregnancy; most reported human experience was short-term, first trimester exposure but no human data are available assessing long-term therapy during pregnancy (e.g., regimen for anthrax exposure).

Congenital defects have been reported with tetracyclines; large doses have caused acute fatty liver necrosis in pregnant women (particularly those with pyelonephritis). Fetal effects may be dose-related. When used during tooth development (second half of pregnancy), tetracyclines may cause permanent yellow-grey-brown discoloration of the teeth; this side effect is more common during prolonged use but has been seen after short-term therapy. Enamel hypoplasia has also been reported.

An expert review of data regarding use of this drug during pregnancy by the Teratogen Information System (TERIS) concluded that substantial teratogenic risk from therapeutic doses during pregnancy is unlikely (data quantity and quality limited to fair); insufficient data to state there is no risk.

Population-based data from the Hungarian Case-Control Surveillance of Congenital Abnormalities revealed that of 32,804 women who had infants with no defects, 63 (0.19%) were treated with this drug during pregnancy. Of 18,515 women who had infants with congenital abnormalities, 56 (0.3%) were treated with this drug. This study showed a weak but marginally statistically significant association with total malformations and use of this drug anytime during pregnancy. This association was not seen when analysis was limited to maternal therapy during organogenesis (i.e., second and third months of gestation), except for a marginal association with neural tube defect based on 2 exposed cases. Data were based on retrospective recall and did not include alcohol or tobacco usage.

In a small prospective study (81 pregnancies), 43 pregnant women were treated with this drug for 10 days during early first trimester. All mothers reported their exposed infants were normal at 1 year of age.

In mass casualty settings after release of biological weapons, the Working Group on Civilian Biodefense has recommended this drug as an alternative drug for prophylaxis and treatment of anthrax, tularemia, and plague. The risk of using this drug during pregnancy is outweighed by the high fatality rates from these infections.

AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.

US FDA pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

See references

Tetracyclines have been considered contraindicated during breastfeeding due to possible staining of infants' dental enamel or bone deposition of tetracyclines; however, a close review of available literature suggests harmful effects are unlikely with short-term use of this drug during lactation as milk levels are low and infant absorption is inhibited by the calcium in breast milk.

According to some experts, this drug is compatible for short courses (e.g., 10 days) if alternative therapy is not appropriate; diarrhea may occur in the nursing infant.

The extent of drug absorption by breastfed infants is unknown. Short-term use in lactating women is not explicitly contraindicated by most manufacturers, but the effects of prolonged drug exposure via breast milk are unknown. Long-term or repeat courses are not recommended during nursing as a theoretical precaution. Theoretical risks of dental staining and inhibition of bone growth in nursing infants are considered unlikely by most experts.

After 2 oral doses (200 mg followed by 100 mg 12 hours later) in 15 nursing mothers, milk drug levels 3 and 24 hours after dosing averaged 0.77 mg/L (range: 0.4 to 1.4 mg/L) and 0.38 mg/L (range: 0.12 to 0.85 mg/L), respectively.

This drug (100 mg/day) was given orally to 10 mothers. On day 2, milk drug levels 3 and 24 hours after dosing averaged 0.82 mg/L (range: 0.37 to 1.24 mg/L) and 0.46 mg/L (range: 0.3 to 0.91 mg/L), respectively. Using peak and trough milk level averages in this study, the estimated intake of an infant only fed breast milk averaged about 6% of the maternal weight-adjusted dose.

Peak milk levels averaged 0.96 mg/L after a single 100 mg dose (n=3) and 1.8 mg/L after a single 200 mg dose (n=3). After 100 mg orally twice a day for 5 days, milk drug levels were about 3.6 mg/L.

In another study, in the immediate postpartum period, peak milk levels were 0.6 mg/L after oral doses of 100 mg (n=3) and averaged 1.1 mg/L after 200 mg (n=11).

After a single 200 mg dose (n=2), milk levels 2, 4, and 6 hours after dosing averaged 0.8, 0.7, and 0.4 mg/L, respectively.

LactMed: Short-term use is considered acceptable; as a precaution (theoretical), prolonged or repeat courses should be avoided throughout breastfeeding.
-IV: The manufacturer makes no recommendation regarding use during lactation.
-Oral: According to some authorities and manufacturers, a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother; according to other authorities and manufacturers, use is contraindicated. Use of the 40 mg capsule formulation is not recommended.

Excreted into human milk: Yes

Comments:
-According to at least 1 manufacturer: Developmental and health benefits of breastfeeding should be considered as well as the mother's clinical need for the drug; potential side effects in the breastfed child due to the drug or the mother's underlying condition should be considered.
-The effects in the nursing infant are unknown; the infant should be monitored for rash and possible effects on the gastrointestinal flora (e.g., diarrhea or candidiasis [thrush, diaper rash]).
-Tetracycline, a related drug, is considered compatible with breastfeeding by the American Academy of Pediatrics.

See references