Phentermine / topiramate Pregnancy and Breastfeeding Warnings

Brand names: Qsymia

Medically reviewed by Drugs.com. Last updated on Sep 16, 2022.

Phentermine / topiramate Pregnancy Warnings

Use is contraindicated.

US FDA pregnancy category: Not assigned

Risk Summary: This drug may cause fetal harm; data from pregnancy registries and epidemiologic studies suggest an increased risk of major congenital malformations.

Comments:
-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.
-Pregnancy testing is recommended in patients of childbearing potential before starting this drug and monthly during therapy; such patients should be advised to use effective contraception during therapy.
-Concomitant use with combined oral contraceptives (COCs) may cause irregular bleeding; patients should be advised to continue taking their COC and contact their health care provider.

PHENTERMINE-TOPIRAMATE: Animal studies have revealed evidence of fetotoxicity but failed to reveal evidence of teratogenicity. Phentermine and topiramate coadministered to rats during organogenesis caused reduced fetal body weights but did not cause fetal malformations at the maximum dose of 3.75 mg/kg phentermine and 25 mg/kg topiramate (about 2 times the maximum recommended human dose [MRHD] based on AUC estimates of each active ingredient). In a similar study in rabbits (same doses administered during organogenesis), no effects of embryofetal development were seen at about 0.1 times (phentermine) and 1 time (topiramate) clinical exposures at the MRHD based on AUC. Significantly lower maternal body weight gain was recorded at these doses in rats and rabbits. There are no controlled data in human pregnancy.
-PHENTERMINE: Animal studies have not been reported. Limited data from studies with the combination of phentermine and topiramate suggested phentermine alone was not teratogenic but resulted in lower body weight and reduced survival of offspring in rats at 5-fold the MRHD of phentermine-topiramate based on AUC. There are no controlled data in human pregnancy.
-TOPIRAMATE: Animal studies have revealed evidence of developmental toxicity, including teratogenicity. In multiple animal species, topiramate administration during organogenesis has caused developmental toxicity (including teratogenicity) at clinically relevant doses. Human data evaluating risk of major congenital malformations, oral clefts, and being small for gestational age (SGA) with topiramate exposure during pregnancy is available from the North American Antiepileptic Drug (NAAED) Pregnancy Registry and from several larger retrospective epidemiologic studies. The NAAED Pregnancy Registry has shown an increased risk of major congenital malformations, including but not limited to oral clefts in infants exposed to topiramate during the first trimester of pregnancy. In the NAAED Pregnancy Registry, the prevalence of oral clefts among topiramate-exposed infants (1.4%) was higher than the prevalence in infants exposed to a reference antiepileptic drug (AED) and in those without exposure to AEDs (0.3% and 0.11%, respectively); it was also higher than the background prevalence in the US (0.17%) as estimated by the US CDC. Larger retrospective epidemiology studies showed topiramate monotherapy exposure in pregnancy was associated with an increased risk of oral clefts of about 2- to 5-fold. Data from the NAAED Pregnancy Registry and population-based birth registry cohort indicate exposure to topiramate in utero is associated with an increased risk of SGA newborns (birth weight less than 10th percentile). In the NAAED Pregnancy Registry, 19.7% of topiramate-exposed newborns were SGA compared to 7.9% of newborns exposed to a reference AED and 5.4% of newborns without AED exposure. The long-term consequences of the SGA findings are not known. There are no controlled data in human pregnancy.

Clinical Considerations:
-Fetal/neonatal adverse reactions: This combination drug can cause metabolic acidosis. The effect of topiramate-induced metabolic acidosis has not been studied during pregnancy, but metabolic acidosis during pregnancy due to other causes can cause decreased fetal growth, decreased fetal oxygenation, and fetal death, and may affect the ability of the fetus to tolerate labor.
-Disease-associated maternal and/or embryofetal risk: Maternal weight loss is not recommended during pregnancy as it may result in fetal harm. Appropriate weight gain based on pre-pregnancy weight is currently recommended for all pregnant patients, including those who are already overweight or obese, due to the obligatory weight gain that occurs in maternal tissues during pregnancy. Maternal obesity increases the risk for congenital malformations (including neural tube defects, cardiac malformations, oral clefts, and limb reduction defects).

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

Phentermine / topiramate Breastfeeding Warnings

TOPIRAMATE:
Maternal doses up to 200 mg/day produce relatively low levels in infant serum. Sedation and diarrhea have been reported occasionally in breastfed infants, but most infants tolerate the drug in milk well. In a few infants, no long-term adverse effects on growth and development have been seen.

Oral topiramate was taken by 3 women daily for epilepsy; the 3 infants were breastfed from birth. Milk level averaged 2.3 mg/L with 150 mg/day (n=1); infant serum levels were about 475 mcg/L. Milk levels averaged from 0.61 to 4.8 mg/L with 200 mg/day (n=2); infant serum levels ranged from undetectable (less than 305 mcg/L) to 713 mcg/L. According to author estimation, the infants received doses between 0.1 and 0.7 mg/kg daily, which was between 3% and 23% of the mother's weight-adjusted dose. Overall, infant plasma levels were about 10% to 20% of maternal plasma levels.

On day 3 or 4 postpartum for routine monitoring, 22 women taking topiramate during pregnancy and postpartum had topiramate in colostrum measured and 19 of their infants had topiramate in serum measured; colostrum topiramate levels averaged 3.5 mg/L and serum level averaged 1.1 mg/L. Milk samples and serum topiramate levels were taken from another 5 mothers and another 6 infants, respectively, between day 7 and 30 (mean 16 days) postpartum; their milk levels averaged 5.9 mg/L and their serum levels averaged 2.2 mg/L. Infant serum levels averaged 51% of simultaneous maternal serum levels.

Use is not recommended.

Excreted into human milk: Yes

Comments:
-No information is available on the use of phentermine during breastfeeding.
-The effects of phentermine in the nursing infant are unknown; there is the potential for serious adverse reaction (including changes in sleep, irritability, hypertension, vomiting, tremor, weight loss) in breastfed infants with maternal use of phentermine.
---Patients should be advised that breastfeeding is not recommended during use of this drug.
-Diarrhea and somnolence have been reported in breastfed infants with maternal use of topiramate.

See references

Further information

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