How Dangerous Is Accutane (Isotretinoin) During Breastfeeding?

How Dangerous Is Accutane (Isotretinoin) During Breastfeeding?

Article Summary

Accutane (isotretinoin) is an oral medication sometimes prescribed for severe acne. It is a vitamin A derivative that causes severe birth defects.

For ethical reasons, there are no studies that investigate the dangers of isotretinoin during breastfeeding, but scientists have examined isotretinoin’s chemical qualities, and the ability of vitamin A and beta-carotene to enter into the breast milk, and have concluded that isotretinoin is not safe for breastfeeding infants.

This prediction is based on the chemical qualities of isotretinoin which likely allow it to enter into breast milk, and the known association of isotretinoin and fetal abnormalities. Therefore, the current recommendation is that both pregnant and breastfeeding women avoid taking isotretinoin to prevent harming the fetus or infant.

The FDA classifies isotretinoin as a category X drug, meaning that research has proven that isotretinoin can cause fetal abnormalities in pregnant women or laboratory animals. In fact, isotretinoin is the most teratogenic (causes birth defects) medication on the market and its effects on the fetus are widespread and severe, including death.1,2Therefore, medical professionals do not prescribe isotretinoin for patients who are pregnant or are planning to become pregnant, and females who do take isotretinoin are required to use two (2) forms of birth control before starting and while taking the medication.

Due to ethical constraints, scientists have been unable to examine the potential dangers of taking isotretinoin while breastfeeding.1Therefore, scientists have relied on attempting to understand whether the chemical qualities of isotretinoin allow it to enter into breast milk. Theoretically, if isotretinoin can pass through into breast milk, it could harm the breastfeeding infant. The research into isotretinoin’s chemical qualities has concluded that it is very likely that when taken by a breastfeeding mother, isotretinoin can cross into the breast milk and harm the infant. Therefore, medical professionals do not recommend that breastfeeding mothers use isotretinoin.1


Drug Transfer into Breast Milk

A breastfeeding mother’s body consistently takes proteins, nutrients, and antibodies from the blood stream and transfers them into breast milk to nourish the feeding infant. When the breastfeeding mother takes oral medication, these drugs also make their way into the blood stream and can occasionally be transferred into breast milk. There are two methods of drug transfer into breast milk, and isotretinoin is likely to be able to transfer through either method:

  1. Paracellular diffusion occurs within the first 3 days after birth, when the drug moves from the blood stream into the breast milk through gaps between breast cells. Paracellular diffusion is a less restrictive drug transfer process than transcellular diffusion, allowing drugs to more easily pass through.
  2. Transcellular diffusion kicks in 3 days after birth, when the gaps between breast cells close and the drug must move through the breast cells themselves to reach the breast milk.

Paracellular Diffusion - Transcellular Diffusion



Regardless of whether it is the first 3 days after birth or after these 3 days have elapsed, medical professionals are extremely careful when it comes to prescribing drugs, like isotretinoin, that can be transferred from the blood stream and into the breast milk through either paracellular or transcellular diffusion.3


6 Chemical Qualities that Support Drug Transfer into Breast Milk

After paracellular diffusion ends and the body closes the gaps between breast cells that appear shortly after birth, the body then must use transcellular diffusion to move nutrients from the blood stream into the breast milk. This process is highly selective, requiring nutrients to meet a variety of chemical qualities in order to pass through the breast cells and into the breast milk. Unfortunately, drugs that have any of these chemical qualities may also be able to pass into the breast milk. When it comes to isotretinoin, it displays 3 of the 6 chemical characteristics that increase the risk that it will pass through breast cells, leading scientists to believe that it will, in fact, pass into breast milk.
 

3 Characteristics of Isotretinoin That Increase Risk of Entering Breast Milk

  • Fat Solubility. Nutrients and drugs that are chemically similar to fat can more easily cross into the breast cell and into the breast milk. Vitamin A is a fat soluble molecule, and isotretinoin, being a vitamin A derivative, retains this quality. Therefore, it can likely easily cross into the breast milk.4
  • Ability of Drug to Enter the Blood Circulation (Oral Bioavailability). When creating oral medication, scientists must consider the ability of the drug to be absorbed by the blood stream. This quality, called oral bioavailability, determines how much of the drug is present in the blood stream, and therefore able move into other bodily fluids like breast milk. Isotretinoin’s bioavailability is 83% when taken with a high fat meal. Therefore, this high bioavailability means that a large percentage of isotretinoin is present in the blood stream and can move into breast milk.4,5
  • The half-life of a drug measures the amount of time it takes for the drug concentration to fall to half of the initial concentration. If a drug has a short half life (1-3 hours), and a mother waits a few hours after taking the drug to breastfeed, that means there can be less of the drug in the blood stream by feeding time. The half-life of isotretinoin is 17-50 hours, therefore potentially exposing the infant to a high concentration of isotretinoin in the breast milk during feedings.6

3 Characteristics of Isotretinoin That Decrease Risk of Entering Breast Milk

  • Molecular Size. There are proteins on the surface of breast cells called pores that allow small molecules to easily pass into the cell. For a molecule to pass through these pores, it must be less than 200 kilodaltons. The size of isotretinoin is 300 kilodaltons. Therefore, isotretinoin cannot pass through breast cell pores. This does not mean it cannot pass into the breast cell in other ways, but it cannot pass through the pores.4
  • Protein Binding Ability. Blood contains proteins which bind to drugs. The more proteins bind to a drug, the less that drug is able to transfer into breast milk. Nearly 100% of isotretinoin in the blood is bound to other blood proteins, therefore potentially limiting its transfer into breast milk.4
  • Measure of Drug Acidity (pKa). Some drugs are more acidic and some are less acidic. The acidity of a drug is measured through calculation of pka. Highly acidic drugs (lower pka) are less likely to enter into and remain in breast milk, while lower acidity drugs (higher pka) are more likely to enter into and remain in breast milk. Isotretinoin is a highly acidic drug with a low pKa of 5. Therefore, the pka of isotretinoin suggests it is more likely to remain in the blood stream than cross into the breast milk.7
     
Chemical Qualities that Support Drug Transfer into Breast Milk



A drug does not have to display all 6 characteristics for it to pass through the breast cell and into the breast milk. Isotretinoin meets only 3 of the 6 qualities, but scientists believe that isotretinoin’s fat solubility, oral bioavailability, and half-life likely gives it the ability to cross into breast milk.


Vitamin A and Beta-Carotene Entrance into Breast Milk

Scientists use vitamin A and beta-carotene to study and predict whether isotretinoin can cross into breast milk because they are chemically similar to isotretinoin and much safer. Naturally, the body transfers vitamin A and beta-carotene into breast milk to support the nutrition of the breastfeeding infant. Research studying vitamin A and beta-carotene supplementation in breastfeeding mothers found that when breastfeeding mothers consume vitamin A or beta-carotene in an oral tablet, it results in an increase in the amount of vitamin A and beta-carotene present in the breast milk. Although ethical constraints prevent a similar study using isotretinoin, scientists predict that, like the chemically similar vitamin A and beta-carotene, isotretinoin can also cross into breast milk and potentially cause harm to the breastfeeding infant.3,5,8-13

For these reasons, doctors recommend that breastfeeding mothers do not to take isotretinoin


Vitamin A and Beta-Carotene Entrance into Breast Milk

The Experts at Acne.org

Our team of medical doctors, biology & chemistry PhDs, and acne experts work hand-in-hand with Dan (Acne.org founder) to provide the most complete information on all things acne. If you find any errors in this article, kindly use this Feedback Form and let us know.

References:

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  2. Rawashdeh N. (2013, May 12). Drugs Contraindicated in Pregnancy. Retrieved May 14, 2016, from Drug Information Center: http://www.just.edu.jo/DIC/Manuals/Drugs contrandicated in pregnancy.pdf
  3. Hale T, and Illet K. (2002). Drug Therapy and Breastfeeding. New York: The Parthenon Publishing Group.
  4. Hale T. (2000). Medications and Mother's Milk. Amarillo, Texas: Pharmasoft Publishing.
  5. U.S. National Library of Medicine. (2016, 04 01). Drugs and Lactation Database. Retrieved 05 14, 2016, from Toxicology Data Network (TOXNET): http://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm
  6. Hale T. (2016). Drug Entry Into Human Milk. Retrieved May 12, 2016, from Infant Risk Center (Texas Tech University Health Sciences Center): http://www.infantrisk.com/content/drug-entry-human-milk
  7. Drug Bank. (2005, June 13). Isotretinoin. Retrieved May 14, 2016, from Drug Bank: http://www.drugbank.ca/drugs/DB00982
  8. Bennett P. (1996). Drugs and Human Lactation. New York: Elsevier.
  9. Canfield, L., Giuliano, A., and Neilson, E “Beta-carotene in Breast Milk and Serum is Increased after a Single Beta-carotene Dose.” American Journal of Clinical Nutrition. 66, 52-61 (1997).
  10. Johnson E, Qin J, Krinsky N, & Russell R. “Beta-carotene isomers in Human Isomer in Human Serum, Breast Milk, and Buccal Mucosa Cells after Continuous Oral Doses of all-trans and 9-cis-beta-carotene.” Journal of Nutrition. 127, 1993-1999 (1997).
  11. Lawrence R, and RM L. (2011). Breastfeeding: A Guide for Medical Profession, 7th ed. Mosby: Maryland Heights.
  12. Ostrea E, Balun J, Winkler R, and Porter T. “Influence of Breast-feeding on the Restoration of the Low Serum Concentration of Vitamin E and Beta-carotene in the Newborn Infant.” American Journal of Obstetrics Gynecology. 154, 1014-1017 (1986).
  13. Thompson, M. (1943). “Carotinaemia in a Suckling.” Archives of Disease in Childhood. 18(94), 112 (1943).
See More References

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