Antibiotics in Pregnancy

Aka: Antibiotics in Pregnancy, Antifungal Medications in Pregnancy, Antiparasitic Medications in Pregnancy, Antiviral Medications in Pregnancy

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II. Background

  1. Pregnancy Categories will be replaced on medication bottles with specific warnings and precautions by 2020 in U.S.
    1. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm425317.htm
    2. Although FDA Pregnancy Categories are no longer FDA designated, they are included here
      1. As of 2018, succinct guidance (to replace ABCDX) on specific drugs in pregnancy is lacking

III. Class B: No risk in controlled animal studies

  1. Antifungal Topical Agents
    1. Nystatin (Mycostatin)
  2. Antiparasitic agents
    1. Metronidazole or Flagyl (after first Trimester)
      1. Short-term use after first trimester appears safe
      2. Avoid single dose therapy (high dose)
      3. Avoid long-term use (due to fetal malformation associations)
    2. Praziquantel - not in Briggs
    3. Permethrin (topical) - not in Briggs (1998)
  3. Anti-Tuberculosis agents
    1. Ethambutol
    2. Didanosine - not in Briggs (1998)
  4. Antiviral agents
    1. Nelfinavir - not in Briggs (1998)
    2. Ritonavir
    3. Saquinavir
    4. Famciclovir
    5. Valacyclovir
  5. Antibiotics
    1. All Cephalosporin Antibiotics (except Moxalactam)
    2. All Erythromycin except Erythromycin Estolate
    3. All Penicillin Antibiotics
    4. Clindamycin
    5. Macrodantin (before 36 weeks)
    6. Sulfa Antibiotics (second trimester only)

IV. Class C: Small risk in controlled animal studies

  1. Antifungal agents
    1. CDC recommends only Topical Antifungal in pregnancy
      1. Avoid Antifungals in first trimester if possible
    2. Terbinafine (Lamisil) - not in Briggs (1998)
    3. Clotrimazole (Mycelex, Lotrimin)
    4. Butoconazole (Femstat)
    5. Miconazole (Monistat)
    6. Amphotericin B
    7. Fluconazole (Diflucan)
      1. As of 2016, evidence of Miscarriage risk, with even 1-2 doses
        1. Mølgaard-Nielsen (2016) JAMA 315(1):58-67 +PMID:26746458 [PubMed]
      2. No fetal adverse effects seen in one study
        1. King (1998) Clin Infect Dis 27:1151-60 [PubMed]
    8. Itraconazole (Sporanox)
    9. Ketoconazole (Nizoral)
      1. Teratogenic and Embryotoxic in animals
      2. Associated with hepatotoxicity
    10. Griseofulvin
      1. Teratogenic and Embryotoxic in animals
  2. Antimalarial agents
    1. Mefloquine (Lariam)
    2. Chloroquine
    3. Primaquine
  3. Antiparasitic agents
    1. Albendazole - not in Briggs (1998)
    2. Ivermectin - not in Briggs (1998)
    3. Mebendazole
    4. Pentamidine
    5. Thiabendazole
    6. Pyrantel
  4. Anti-Tuberculosis agents
    1. Dapsone
    2. Isoniazid (INH)
    3. Pyrazinamide
    4. Rifampin
  5. Antiviral agents
    1. Lamivudine
    2. Stavudine
    3. Zalcitabine
    4. Zidovudine
    5. Delavirdine - not in Briggs (1998)
    6. Nevirapine
    7. Indinavir
    8. Cidofovir
    9. Foscarnet
    10. Ganciclovir
    11. Acyclovir
    12. Amantadine
    13. Rimantadine
    14. Interferon alpha
  6. Antibiotics
    1. Imipenem-Cilastin
    2. All Fluoroquinolone antibiotics (avoid in pregnancy due to cartilage damage risk)
    3. Macrolides in general (including Azithromycin)
      1. May increase heart defects with first trimester exposure of 5-7 days
      2. Previously only Clarithromycin was considered a potential Teratogen (Cleft Lip association)
      3. Fan (2020) BMJ 368: m331 +PMID:32075790 [PubMed]
    4. Pediazole - not in Briggs (1998)
    5. Sulfisoxazole - not in Briggs (1998)
    6. Trimethoprim (Folic Acid Antagonist)
      1. May be used as part of Trimethoprim-Sulfamethoxazole (Bactrim, Septra) in second trimester
    7. Vancomycin
    8. Chloramphenicol
    9. Gentamicin

V. Class D: Strong evidence of risk to the human fetus

  1. Antiparasitic agents
    1. Metronidazole or Flagyl (First Trimester)
      1. Brief use may be safe in first trimester
      2. Burtin (1995) Am J Obstet Gynecol 172:525-9 [PubMed]
  2. Antibiotics
    1. Amikacin (Class D per manufacturer)
    2. Kanamycin
    3. Streptomycin
    4. Tobramycin (Class D per manufacturer)
    5. Sulfa (Third Trimester)
    6. All Tetracycline Antibiotics
      1. Tetracycline
      2. Minocycline
      3. Doxycycline
        1. Does not appear to have same adverse effects as other Tetracyclines
        2. May be considered in serious infections without good alternatives (e.g. Rocky Mountain Spotted Fever)
    7. Erythromycin Estolate (llosone)
      1. Due to hepatotoxicity in pregnant women
      2. McCormack (1977) Antimicrob Agents Chemother 12:630 [PubMed]
    8. Macrobid and Nitrofurantoin (Third Trimester)
      1. Do not use either of these past 36 weeks
      2. Can cause Hemolytic Anemia in newborns
      3. Related to immature liver and G6PD Deficiency
  3. Vaccines
    1. Yellow Fever Vaccine

VI. Class X: Very high risk to the human fetus

  1. Antimalarial agents
    1. Quinine
  2. Antiviral agents
    1. Ribavirin
    2. Rebetron - not in Briggs (1998)
  3. Vaccines
    1. MeaslesVaccine
    2. Mumps Vaccine
    3. RubellaVaccine
    4. Small PoxVaccine
    5. TC-83 Venezuelan Equine EncephalitisVaccine
    6. Varicella Vaccine
      1. Risk if vaccinated within 4 weeks of conception
      2. Theoretic risk only; not an indication for EAB

VII. References

  1. (2017) Presc Lett 24(5): 26
  2. Briggs (1998) Drugs in Pregnancy and Lactation, 5th ed
  3. Black (2003) Am Fam Physician 67(12):2517-24 [PubMed]
  4. Larimore (2000) Prim Care 27(1):35-53 [PubMed]

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