Bupivacaine / meloxicam Pregnancy and Breastfeeding Warnings

Brand names: Zynrelef

Medically reviewed by Drugs.com. Last updated on Apr 2, 2024.

Bupivacaine / meloxicam Pregnancy Warnings

Avoid use at about 30 weeks gestation and later.

US FDA pregnancy category: Not assigned

Risk summary: Use of NSAIDs at about 30 weeks gestation and later may produce premature closure of the fetal ductus arteriosus; use of NSAIDs at about 20 weeks gestation and later is associated with fetal renal dysfunction leading to oligohydramnios and potentially neonatal renal impairment.

Comments:
-There is no data on use in pregnant women to know this drugs risks, including the risk of fetal harm or reproductive effects.
-Fetal renal dysfunction leading to oligohydramnios and potentially neonatal renal impairment is typically seen after days to weeks of NSAID treatment, but has infrequently occurred as soon as 48 hours after NSAID initiation.
-Oligohydramnios is often, but not always, reversible with drug discontinuation.
-Prolonged oligohydramnios may lead to complications such as limb contractures and delayed lung maturation.
-Some postmarketing cases of impaired neonatal renal functions have required invasive procedures such as exchange transfusion or dialysis.
-Limitations of postmarketing reports and studies includes lack of a control group, limited information on dose, duration, and timing of exposure, and use of other medications. Data on outcomes mostly involved preterm infants, making generalizability of the risks to a full-term infant uncertain.
-If NSAID treatment is needed between 20- and 30-weeks gestation, use the lowest effective dose and consider ultrasound monitoring for oligohydramnios.
-Treat oligohydramnios according to clinical practice.
-Animal studies of NSAIDs, including meloxicam, showed inhibited prostaglandin synthesis, delayed parturition, and increased stillbirth incidence.

Animal studies are not available for the combination product. There are no controlled data in human pregnancy.

Bupivacaine:
Animal studies of subcutaneous administration during organogenesis, at doses comparable to the maximum recommended human dose (MRHD) showed no embryofetal effects in the high dose which caused increased maternal lethality in rats, and increased embryofetal deaths at the high dose in the absence of maternal toxicity in rabbits; the fetal No Observed Adverse Effect Level was approximately 0.3 times the MRHD.

Meloxicam:
Animal data: Animal studies of oral administration of meloxicam during organogenesis at doses 3 times the 12 mg meloxicam dose showed no embryofetal malformations in rats. In rabbits, administration throughout embryogenesis produced increased incidence of septal defects of the heart at 97 times the MRHD; the No Effect Level was 32 times the MRHD. Oral administration to rats from late gestation through lactation showed increased dystocia incidence, delayed parturition, and decreased offspring survival at dose 0.1 times the MRHD or greater.

Fertility:
Prostaglandin-mediated NSAIDs, including meloxicam, may delay or rupture ovarian follicles, which is associated with reversible infertility in some patients. Animal studies showed prostaglandin synthesis inhibitors have the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. Small human studies showed a reversible delay in ovulation with NSAID use. An animal study of oral meloxicam for 35 days showed decreased sperm count and motility, and histopathological evidence of testicular degeneration at 0.8 times the MRHD; it is not known if these effects are reversible.


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

Bupivacaine / meloxicam Breastfeeding Warnings

The manufacturer makes no recommendation regarding use during lactation.

Excreted into human milk: Yes (bupivacaine)/Data not available (meloxicam)
Excreted into animal milk: Yes (meloxicam)

Comments:
-There is no information regarding this drug on the effects on a breastfed infant, or effects on milk production.
-Limited literature reports low levels of bupivacaine and its primary metabolite, pipecoloxylidine (PXX) in human milk.
-Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for this medication as well as any potential adverse effects from this drug or the underlying maternal condition.

-After administration of this product to lactating animals, bupivacaine and meloxicam were detected in the milk, but only bupivacaine was detected in the plasma of the suckling offspring.
-Meloxicam was present in rat milk at concentrations higher than those in plasma.

See references

Further information

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