On October 7, 2020, the journal Breastfeeding Medicine published an article by Philip O Anderson, which assessed the use of the best known drugs during breastfeeding that could be effective against COVID-19.
Used to treat Ebola virus infection (Martínez 2020) Also effective against other viruses, approved for the treatment of COVID-19 coronavirus (Aleissa 2020, Dong 2020, Martínez 2020, SEFH 2020). It is moderately effective in reducing symptoms and accelerating recovery in hospitalized patients with severe disease.
Based on its pharmacokinetic characteristics, its excretion into breast milk in significant concentrations seems unlikely. In addition, remdesivir is given intravenously (IV) because it is poorly absorbed orally. Accordingly, infants are unlikely to absorb a clinically significant amount of the drug in breast milk (i.e., orally).
Moreover, infants and children under 5 years of age received intravenous remdesivir for Ebola without any adverse reactions (Dörnemann 2017, Mulangu, 2019, Aleissa 2020). The Food and Drug Administration (FDA) approves its use for the treatment of COVID-19 in children over 3.5 kg (FDA 2020).
Philip O Anderson, 2020 concludes that with this limited information, mothers receiving remdesivir should not stop breastfeeding. Until further evidence is available, remdesivir should be used with close supervision of infants while breastfeeding.
Used to treat influenza, is being tested for use against COVID-19, but has not yet been approved by the FDA. Some preliminary COVID-19 results from outside the United States appear promising, but no high-quality studies have been reported. Possible side effects of favipiravir include diarrhea, decreased neutrophils, and increased transaminase and uric acid levels (Taisho 2014).
Its pharmacokinetic data suggest that it will pass into breast milk and be absorbed by the infant’s body in small quantities. However, there is no information yet on the use of favipiravir during breastfeeding or on its excretion in breast milk. Philip O Anderson, 2020 notes that when favipiravir is prescribed to a nursing mother, typical adverse reactions in a breastfed baby should be monitored.
E-lactancia.org rates this drug as a low risk drug and recommends the use of safer alternatives (very low risk drugs), especially in the neonatal period and in the case of prematurity, until more published data on favipiravir becomes available.
HIV protease inhibitors (atazanavir, darunavir + cobicistat, and lopinavir + ritonavir)
The US National Institutes of Health (NIH) discourages the use of HIV protease inhibitors except in the context of clinical trials, due to adverse pharmacodynamics and negative clinical trial data.
There is no published information on the use of darunavir with or without cobicistat during breastfeeding. According to three women, the amount of atazanavir in milk appears to be low. Lopinavir is the best studied — information about it and ritonavir was in this article .
Interferon beta-1b and ribavirin is a combination previously used to treat chronic hepatitis C infection and is currently being investigated for use in COVID-19. Interferon beta-1a is also being studied in combination with remdesivir in hospitalized patients.
Interferon beta-1a levels in breast milk are negligible. In addition, because interferon is poorly absorbed when taken orally, it is unlikely that it will enter the infant’s bloodstream. Many women breastfed while taking interferon beta-1a with no reported side effects in infants. According to experts, beta-interferons are acceptable for breastfeeding.
Ribavirin is administered directly to infants by inhalation to treat respiratory syncytial virus (RSV) infection. It is unlikely to pass into breast milk in significant quantities. Low oral bioavailability prevents the drug from entering the infant’s plasma from milk. The exception is premature babies and the neonatal period, since in such cases, increased intestinal permeability can be observed.
E-lactancia.org classifies ribavirin as a low-risk drug and considers it compatible with breastfeeding for short-term exposure, but long-term treatment should be treated with caution.
Antibody therapy by infusion of plasma obtained from patients who have recovered from COVID-19 can prevent infection or reduce the severity of the disease. Most likely, such therapy will be effective for prevention or in the early stages of the disease.
Also, at the beginning of the pandemic, Chinese doctors injected intravenous immunoglobulin to treat critically ill patients. When administered promptly (within 48 hours after admission to the hospital), this reduced mortality, hospital stay and the frequency of ventilator use.
Philip O Anderson, 2020 notes that immunoglobulin is a normal constituent of breast milk, so neither convalescent plasma nor intravenous administration of immunoglobulin to the mother pose a risk to the infant.
Work is also underway to develop monoclonal antibodies against SARS-CoV-2 (the virus that causes COVID-19) in the form of single or combination of highly active antibodies. These antibodies are found in breast milk in very small amounts due to their high molecular weight. In addition, they have poor bioavailability for breastfed babies because they are likely to be degraded in the infant’s gastrointestinal tract, at least in the first few days after birth. Thus, if monoclonal antibodies against SARS-CoV-2 are used, they are unlikely to pose a danger to an infant.
A case series and two retrospective review studies showed that famotidine reduced the risk of intubation and death by about 60% in hospitalized patients.
Famotidine is found in milk in small amounts when using a dosage of more than 40 mg / day. However, e-lactancia.org classifies it as a very low-risk drug, since the amount excreted in breast milk is much less than the dose administered to newborns and infants with gastroesophageal reflux disorders.
Antimalarial drugs (chloroquine and hydroxychloroquine)
The antimalarial drugs chloroquine and hydroxychloroquine have been widely reported in the news, but these drugs have not shown good results against COVID-19 in controlled clinical trials. The FDA has issued a Drug Safety Notice discouraging the use of these drugs outside of clinical trials because of the risk of serious cardiac arrhythmias, and they are not recommended for the treatment of outpatients.
E-lactancia.org classifies both drugs as very low risk drugs. They enter breast milk in small quantities, which are much lower than the dose used for infants (Peng 2019, Liu 2016, Cissoko 2010, Costedoat 2002, Ostensen 1985, Nation 1984). Infants whose mothers received hydroxychloroquine did not have developmental, vision or hearing problems (Peng 2019, Motta 2005 and 2002, Cimaz 2004, Tincani 2001). Several medical associations and experts consider its use to be compatible with breastfeeding (Hale, Sammaritano 2020, Briggs 2017, Flint 2016, Götestam 2016, Kavanaugh 2015, Schaefer 2015). Chlorine is not recommended for patients with glucose-6-phosphate dehydrogenase deficiency.
Azithromycin has been used alone and with hydroxychloroquine. Most of the trials were of modest quality (eg, retrospective, open-label) and the results were not impressive. The combination with hydroxychloroquine can cause a prolongation of the QT interval and an increase in the level of liver enzymes. The NIH does not recommend the use of such a combination except in clinical trials due to its toxic potential.
Due to the fact that azithromycin is found in breast milk in small quantities (much less than is used to treat babies themselves), it belongs to the drugs with a very low risk. The expert authors believe that azithromycin is compatible with breastfeeding (Butler 2014, Kong 2013, Khrianin 2010, Chen 2010, Goldstein 2009, Mahadevan 2006, Bar-Oz 2003, Chin 2001).
As with any antibiotic, it can affect the gastrointestinal flora, which can lead to diarrheal diseases, candidiasis (thrush, diaper rash).
An uncontrolled retrospective study showed a reduced risk of mortality in patients taking ivermectin.
The site e-lactancia.org classifies it as a very low-risk drug because it only gets into milk in small quantities (Rodari 2020, Ogbuokiri 1993). There were no side effects in infants whose mothers took this drug (Porto 2003, Ogbuokiri 1994 and 1993).
Clinicaltrials.gov has documented numerous studies using nitazoxanide alone or in combination with other drugs to treat COVID-19, but results are not yet available.
After oral administration, nitazoxanide is not detected in the bloodstream, but is rapidly converted to active metabolites, tizoxanide and tizoxanide glucuronide, which are found in the mother’s plasma. Information from one mother shows that at a dosage of 500 mg nitazoxanide, low levels of tizoxanide are found in breast milk. Dosages in COVID-19 studies are around 1–2 g / day. Some experts consider its use during breastfeeding to be safe (Hale, 2017, p. 710, Briggs, 2017, Lactmed, 2013). E-lactancia.org classifies it as a very low risk drug.
Limited evidence from peer-reviewed observational studies suggests that supplemental vitamin D may reduce the severity of COVID-19 in people with vitamin D deficiency. There is no evidence that high doses of vitamin D can cure disease or help people with normal vitamin D levels.
Vitamin D is a common ingredient in breast milk. Maternal daily doses of vitamin D equal to or> 4,000 IU (100 mcg) may be expected to correspond to an infant’s daily requirement (at least 400 IU), depending on the mother.
Previously, it was also proposed to use the drug sarilumab for the treatment of severe forms of COVID-19, but it has not been confirmed to be effective. The site e-lactancia.org classifies it as a low risk drug. It is assumed that it penetrates into breast milk in small quantities and is rather poorly absorbed orally, but it is confused by its very long half-life (26 days). Götestam-EULAR 2016 believes that breastfeeding should not be discouraged when using sarilumab unless other options are available.
A very low risk alternative to Sarilumab (according to e-lactancia.org) is tocilizumab, which is also being experimentally used to treat the coronavirus COVID-19 (Alzghari 2020, SEFH 2020). Research results are conflicting.
It passes into breast milk in small quantities and is poorly absorbed orally. Plasma levels in infants whose mothers were treated with this drug were undetectable or very low even during the neonatal period (Saito, 2019). Several medical associations and experts believe that the use of this medication is compatible, or probably compatible with breastfeeding (Sammaritano 2020, Briggs 2017, Götestam 2016) if there are no other safer options available.