New Pregnancy and Lactation Labelling Rule- FDA

With the complexity of the diseases comes the complexity of prescribing the medicines in pregnant ladies and the assessment using the earlier criteria of A,B, C, D and X was even more difficult. Therefore a more evidence based approach was needed which can help the healthcare providers in judging the medications better.

The previous labelling had five categories:

  • A – Adequate well controlled studies in pregnant women have failed to demonstrate a risk in fetus in the first trimester of pregnancy, eg- Doxylamine, Folic acid, Levothyroxine
  • B- Animal reproduction studies have failed to demonstrate a risk to the fetus, and there are no adequate and well-controlled studies in pregnant women, or animal reproduction studies have shown adverse effects, but well controlled studies in pregnant women have shown no adverse effects to the fetus. eg- Amoxicillin, Loratidine, Ondansetron
  • C- Animal reproduction studies have shown an adverse effect on the fetus, or there are no animal reproduction studies and no well controlled studies in humans- eg- Fluconazole, Metoprolol, Sertaline
  • D- Positive evidences of fetal risk, but benefits may outweigh the risks- eg- Lisinopril, Lithium, Phenytoin
  • X- Positive evidence of fetal risk, and risks clearly outweigh any possible benefit eg- Methotrexate, Simvastatin, Warfarin

As we can see, the previous categorisation possesses some issues such as oversimplification of the drug classifications , for eg- 60% of the medicines fall under category C and this category includes both the adverse effects in animal studies as well as no studies found while doing animal studies. So the evidence of risks and no risks are allowed to be kept under the same category. The severity is based on the amount of data availability and not by of how severe the risks can be.

A mental-model research study done by FDA also found out that health care professionals depended more on the categories and not on the additional information given on the label. The participants in the study suggested that the information provided should be more evidence based.

What is the change ?

FDA will remove the letter categories and add a new section the following table should make it more clear.

New PLLR
Pregnancy risk letters eliminated
8.1 and 8.2 combined to form one section – 8.1 Pregnancy

– Pregnancy exposure registry
-Risk summary
-Clinical considerations
-Data
8.3 Nursing mothers section becomes section – 8.2 Lactation
-Risk Summary
-Clinical Considerations
-Data
Section 8.3 will now have- Females and males reproductive potential

-Pregnancy testing
-Contraception
-Infertility

The Risk Summary sections will try to tell the health care practitioners the human, animal, and pharmacological risk data available, a background of information about birth defects and miscarriages in the US and general population. In the 8.2 section Lactation , it will tell about the presence of the drug in the human milk and inform about the risk benefit ratio related to use.

Clinical considerations will inform about the disease associated with maternal and fetal risks, relevant dose adjustments, labor and delivery information.

The new section which is Females and males reproductive potential is basically to be utilized in certain situations, such as :-

  • if there is a need to test for pregnancy or if the person should take any contraception
  • if there are any human or animal data suggesting drug associated effects on fertility or preimplantation loss effects

Clinical Impact

Although the effort to improve the labelling seems to be good, but the challenges will remain. Some experts say that the removal of categories might involve complexities in giving detail descriptions in the mentioned sections, and it may be time taking to finally make a decisions.

Conclusion

The deputy director of office of the New Drugs, FDA stated that the there was a need to take individualised decisions in order to carefully prescribe the medicines during pregnancy, lactation or during the nursing and that the former system of categories was overly simplistic and was misunderstood as a grading system. Nevertheless the cases of pregnancies are complex, and it demanded a more evidence based approach.

References

  1. Food and Drug Administration. Content and format of labeling for human prescription drug and biological products: requirements for pregnancy and lactation labeling. Fed Regist. 2014;79(233):72064–72103. Available at: www.gpo.gov/fdsys/pkg/FR-2014-12-04/pdf/2014-28241.pdf.
  2. Food and Drug Administration. Pregnancy, lactation, and reproductive potential: labeling for human prescription drug and biological products—content and format: guidance for industry. Dec, 2014 Food and Drug Administration. Content and format of labeling for human prescription drug and biological products: requirements for pregnancy and lactation labeling. Fed Regist. 2014;79(233):72064–72103. Available at: www.gpo.gov/fdsys/pkg/FR-2014-12-04/pdf/2014-28241.pdf
  3. Food and Drug Administration. Novel drugs 2015. Jan, 2016. Available at: www.fda.gov/downloads/Drugs/DevelopmentApprovalPro-cess/DrugInnovation/UCM485053.pdf.

2 Comments

  1. it is very important to know the safety profile of medicines in pregnancy. As a rule, i try to avoid prescribing any medicine during the 1st trimester of pregnancy but psychiatric patients often suffer a relapse. So i try to maintain on a minimum number of time tested medicines. As for anti epileptic medicines, I prescribe levitiracetam instead of phenytoin or valproate.

    Like

    1. That’s true , a lot of times we have to choose benefits over the risks, and going low and slow is a nice way of keeping the risks low in these cases.

      Like

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