Analgesic Medications in Pregnancy


Analgesic Medications in Pregnancy, Anesthetic Medications in Pregnancy, Rheumatologic Preparations in Pregnancy, Analgesic Medications in Lactation

  • 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 listed, they are included here
      1. As of 2018, succinct guidance (to replace ABCDX) on specific drugs in pregnancy is lacking
  • Precautions
  • Pregnancy
  1. NSAIDs should generally be avoided in pregnancy (despite Category B before third trimester)
    1. Miscarriage risk in first trimester
    2. Premature Ductus Arteriosus closure in third trimester
    3. Second trimester use in second trimester had been considered safe until re-labeling in 2020
      1. Associated with fetal renal complications and oligohydramnios
      2. New guidelines recommend avoiding after 20 weeks gestation
      3. https://www.fda.gov/media/142967/download
  2. Tramadol should be avoided in pregnancy
    1. Second trimester use may be safe
    2. Fetal toxicity in animals (highest risk in first trimester)
    3. Respiratory problems and withdrawal symptoms in newborn (avoid in third trimester)
  3. Opioids should be avoided in pregnancy unless there is no viable alternative
    1. First trimester use is associated with heart defects and Neural Tube Defects (e.g. Spina bifida)
    2. Late pregnancy use is associated with Opioid Withdrawal (neonatal abstinence syndrome)
      1. Neonatal Respiratory Distress may also occur
    3. (2017) Presc Lett 24(11): 64
    4. (2017) Obstet Gynecol 130(2):e81-e94 +PMID:28742676 [PubMed]
    5. Reddy (2017) Obstet Gynecol 130(1):10-28 +PMID:28594753 [PubMed]
  • Class B
  • No risk in controlled animal studies
  1. Acetaminophen (Tylenol)
    1. Analgesic of choice in pregnancy
    2. May be associated with increased risk of ADHD in children with prolonged regular use (>4 to 6 weeks, esp. third trimester)
      1. However Acetaminophen association with ADHD is without evidence of causality
      2. Cooper (2014) JAMA Pediatr 168(4):306-307 [PubMed]
      3. Gou (2019) Aust N Z J Psychiatry 53(3): 195-206 [PubMed]
      4. Matosich (2024) Am Fam Physician 109(1): 81-2 [PubMed]
      5. Sznajder (2022) PLoS One 17(9): e0272593 [PubMed]
  2. Opioids (Class D if prolonged use or high dose)
    1. Nalbuphine (Nubain)
    2. Meperidine (Demerol)
    3. Butorphanol (Stadol)
    4. Fentanyl (Duragesic)
    5. Hydromorphone (Dilaudid)
    6. Methadone (Dolophine)
    7. Morphine Sulfate
    8. Oxycodone (Percocet)
  3. NSAIDs (first and second trimester only, but see precaution above)
    1. Ibuprofen (Motrin)
    2. Indomethacin (Indocin)
    3. Ketoprofen (Orudis)
    4. Naproxen (Naprosyn)
    5. Piroxicam (Feldene)
    6. Sulindac (Clinoril)
  • Class C
  • Small risk in controlled animal studies
  1. Opioids (Class D if prolonged use or high dose)
    1. Codeine (Tylenol with Codeine)
    2. Hydrocodone (Vicodin)
    3. Tramadol (Ultram)
    4. Propoxyphene (Darvocet)
    5. Buprenorphine
  2. Barbiturates
    1. Butalbital (Fiorinal)
      1. Class D if prolonged use or high dose
  3. NSAIDs (first or second trimester only)
    1. Aspirin
    2. Etodolac (Lodine)
    3. Ketorolac (Toradol)
    4. Nabumetone (Relafen)
    5. Oxaprozin (Daypro)
  • Class D
  • Strong evidence of risk to the human fetus
  1. Aspirin
    1. Used only with specific indications in pregnancy
    2. Risk of neonatal Hemorrhage, IUGR, perinatal death
    3. Low dose Aspirin may be safer
      1. Hauth (1995) Obstet Gynecol 85:1055-8 [PubMed]
  2. All NSAIDs (Third Trimester)
  3. Prolonged use or high dose of any Opioid
  4. Prolonged use or high dose Butalbital (Fiorinal)
  5. General Anesthesia - not in Briggs (1998)
  1. Acetaminophen (Tylenol)
  2. Ibuprofen (Motrin)
  3. Tramadol
    1. Small amount crosses into Breast Milk
  1. Opioids that are converted to active metabolites by CYP2D6
    1. Codeine
    2. Hydrocodone
    3. Oxycodone
  2. Risk of Overdose in babies if mother is a ultra-rapid CYP2D6 metabolizer
    1. Ultrarapid CYP2D6 metabolism occurs in 10% caucasians, 3% african americans, 1% chinese and hispanic
  3. Preacutions if these Opioids are used in Lactation
    1. Avoid use beyond 4 days of life when milk intake increasing substantially
      1. Consider pumping and dumping while taking the Opioid
      2. Transition to Acetaminophen or NSAID as soon as possible
    2. Use the lowest effective dose of the shortest acting agent
    3. Limit dosing to immediately after feeding
  • References
  1. Briggs (1998) Drugs in Pregnancy and Lactation, 5th ed
  2. (2012) Presc Lett 19(2): 11
  3. Black (2003) Am Fam Physician 67(12):2517-24 [PubMed]
  4. Larimore (2000) Prim Care 27(1):35-53 [PubMed]