Taking COVID-19 Drugs in Pregnancy

COVID-19 Impacts Labor & Delivery

How are pregnant women impacted by coronavirus?

Good news: there have not been any confirmed cases of mothers transferring coronavirus to the baby in utero.

Bad news: concerning labor & delivery outcomes in COVID-19 infected Chinese moms (who were NOT known to receive the drugs described below).

A recent article in the Journal of Infection detailed the delivery outcomes from thirteen Chinese women who were pregnant and tested + for coronavirus.

• Ages 22 to 36 years old

• No pre-existing health conditions (besides pregnancy)

• Two women were in their second trimesters, and the other eleven women were in their third trimesters

• Six of the eleven women in their third trimester —> early labor related to fetal distress, premature membrane rupture, and even one stillbirth.

• The two women who were in their second trimesters did NOT go into early labor or have any other fetal consequences noted

Since a lot of these pregnancies had complications, having a rapid and reliable treatment for COVID-19 could improve the health of infected mothers and babies.

Promising Drugs to Treat COVID-19

CHLOROQUINE

• reports from China suggest effective against COVID-19

• passes through the placenta and into breastmilk

  • caused vision problems and blindness in mice and monkey babies

  • no birth defects definitively seen in human studies in Thailand and in New Guinea on pregnant moms requiring malaria prophylaxis

  • Drugs in Pregnancy and Lactation

    • chloroquine is not likely cause of human birth defects

    • benefits outweigh risks of preventing and treating malaria

      —> extrapolate to treatment of COVID-19?

HYDROXYCHLOROQUINE

• less toxic, just as effective as chloroquine

• reports from southern France suggest effectiveness against COVID-19

  • hydroxychloroquine = 14 patients. Viral cure = 57.1%

  • hydroxychloroquine + azithromycin = 6 patients. Viral cure = 100%

  • control group (no drug) = 16 patients. Viral cure = 12.5%

• national shortage - FDA allowing Indian manufacturer with quality control deficiencies to increase production for U.S. consumption

Cure of Coronavirus at Six Days (%)

This study inspiring the hydroxychloroquine shortage specifically excluded pregnant women. Given that it is safe to use in pregnancy in other conditions, plus it is generally considered to be a safer drug than chloroquine, it would be reasonable to assume that it would be safe in pregnant women infected with COVID-19. Of the drugs being tested to treat COVID-19, hydroxychloroquine is the drug I feel most confident endorsing for safety and efficacy in pregnant women at this time. I’d also recommend taking it with azithromycin to increase chances of clearing the virus. 

Though I’ve given my endorsement, I would be remiss as a pharmacist if I didn’t discuss another promising drug that’s gotten a lot of attention lately. It’s an antiviral called remdesivir, which is NOT officially FDA approved for any illness in the U.S. It is allowed for “compassionate use,” meaning that a patient may be able to gain access to the drug if in a life-threatening condition and there isn’t a good alternative treatment available. The manufacturer of this drug has seen such a surge in requests to use remdesivir during this pandemic that they just cut off new requests to use this drug EXCEPT for pregnant women and in children.

So, while it remains available for pregnant women, is it actually safe and effective? In 2018/2019, remdesivir was given to six pregnant Congolese women infected with Ebola who were enrolled in a clinical trial looking at four investigational drugs to potentially treat that illness.

This trial was published in Dec 2019 in the New England Journal of Medicine; unfortunately, after looking over the study and all of the published information, there is very little detail on how these six pregnant women responded to remdesivir. We don’t know their ages, how far along they were in their pregnancies, etc. One reason that the trial may have given so little focus to so few pregnant women taking remdesivir is because two other drugs in the study were found to be more effective at treating Ebola, so they stopped giving remdesivir in favor of other drugs. I gleaned the study for details and read in the supplementary index about the adverse events broken down by patient and drug. One of the other experimental drugs mentioned one baby born with hydrocephalus and one with a shortened umbilical cord. Because these adverse outcomes were mentioned in a drug that was NOT remdesivir, can we assume that remdesivir does not cause fetal harm? 

We still have too little information - six pregnant women taking a drug is simply not enough to draw useful conclusions. In the short-term, we will have to look at press releases for pregnant women who took remdesivir through compassionate use. According to upcoming U.S. studies listed on clinicaltrials.gov, only one of the three remdesivir trials is specifically excluding pregnant women from participating, so hopefully we will have some concrete data once the two inclusive trials have ended. To see the studies included in this podcast, please check out “yourfertilitypharmacist.com.”

Resources

Jurvetson, S. Coronavirus Toy. No changes made to the adorable image, which can be found here on Flickr.

Briggs, G. G., Freeman, R. K., & Yaffe, S. J. (2017). Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. Tenth edition. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins Health.

Centers for Disease Control and Prevention. (2020). Information for Clinicians on Therapeutic Options for COVID-19 Patients. https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html

ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). [cited 2020 Mar 25]. Available from: https://clinicaltrials.gov/ct2/results?cond=Coronavirus&term=remdesivir&cntry=&state=&city=&dist=&Search=Search

Favre G et al. 2019-nCoV epidemic: what about pregnancies? Lancet. 2020 Feb 22;395(10224):e40. https://doi.org/10.1016/S0140-6736(20)30311-1

Favre G et al. (2020). Guidelines for pregnant women with suspected SARS-CoV-2 infection. Lancet Infect Dis. https://doi.org/10.1016/S1473-3099(20)30157-2

FDA News Release. Coronavirus (COVID-19) Update: FDA Continues to Facilitate Development of Treatments. March 19, 2020. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-continues-facilitate-development-treatments

FDA Inspection Report, India’s Ipca Laboratories Ltd. https://www.fda.gov/media/130650/download

Gilead Sciences, Inc. Update On The Company’s Ongoing Response To COVID-19. https://www.gilead.com/purpose/advancing-global-health/covid-19

Karunajeewa HA, et al. Antimicrobial Agents and Chemotherapy. Feb 2010, 54 (3) 1186-1192. https://aac.asm.org/content/54/3/1186

Liang H, Acharya G. Novel corona virus disease (COVID‐19) in pregnancy: What clinical recommendations to follow? Acta Obstet Gynecol Scand. 2020 Mar 5. https://doi.org/10.1111/aogs.13836

Liu Y, et al. Clinical manifestations and outcome of SARS-CoV-2 infection during pregnancy. J Infect. 2020; https://doi.org/10.1016/j.jinf.2020.02.028

Mulangu S, et al. A randomized, controlled trial of Ebola virus disease therapeutics. N Engl J Med. 2019 Nov 27. doi:10.1056/NEJMoa1910993

Zhou D, Dai SM, and Tong Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicrob Chemother. 2020 Mar 20. pii: dkaa114. doi: 10.1093/jac/dkaa114.

Zhu H, et al. Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia. Transl Pediatr. 2020 Feb;9(1):51-60. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036645/