Benefit should outweigh risk

AU TGA pregnancy category: B3
US FDA pregnancy category: Not Assigned

Risk Summary: The limited data with this drug in pregnant women is not sufficient to inform a drug-associated risk of major birth defects and miscarriage; animal studies suggest there may be a risk to the fetus from exposure to lixisenatide.

Comments:
-Insulin therapy is considered a drug of choice during pregnancy.
-There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy.
-Some authorities advise against use of this drug in women of childbearing potential not using contraception.

Studies in pregnant rats and rabbits receiving lixisenatide at doses of 1 and 6 times the recommended human dose during organogenesis, respectively, have been associated with visceral closure and skeletal defects at exposures that decreased maternal food intake and weight gain. Published studies with insulin glargine have not reported a clear association with major birth defects or miscarriage risk. Poorly controlled diabetes in pregnancy increases the maternal risks for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery and delivery complications; and fetal risks for major birth defects, still birth, and macrosomia related morbidity. There are no controlled data in human pregnancy.

Patients with diabetes or a history of gestational diabetes should maintain good metabolic control before conception and during pregnancy. Insulin requirements may decrease during the first trimester; generally, increase during the second and third trimesters, and rapidly decline after delivery. Careful monitoring of glucose control is essential.

AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

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.

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Benefit should outweigh risk

Excreted into human milk: Insulin glargine (yes); Lixisenatide (unknown)
Excreted into animal milk: Yes (lixisenatide)

Comments:
-There is no information on the effects of this combination product on the breastfed infant, or the effects on milk production.
-Insulin glargine is considered compatible with breastfeeding; women who are breastfeeding may require adjustments of their insulin dose.

Exogenous insulins, including insulin glargine appear to be excreted into breast milk. Insulin is a protein that is inactivated if taken by mouth. If absorbed, it would be destroyed in the digestive tract of the infant. There is no information on the presence of lixisenatide in human milk. In lactating rats, milk transfer of lixisenatide and its metabolites were low (9.4%) and levels of unchanged drug in the gastric contents of weaning offspring was negligible (0.01%).

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