The current health emergency has put humanity to the test. This is the most serious health crisis of the last century, although gradually a favorable outlook is beginning to be seen. One of the keys has been progress in vaccination campaigns. In addition, another type of drugs to care for infected patients. But as with other diseases, there are certain contraindications of all medicines against Covid-19 that must be followed.
In this sense, it is essential to follow the manufacturers’ instructions to obtain the maximum possible benefit and not affect patients. Misusing treatments is also harmful to you because you can be accused of a Medical negligence.
With this in mind, the Ministry of Health (SSa) has a document entitled Clinical guide for the treatment of Covid-19 in Mexico. Its function is to function as a support for the medical staff to use all pharmacological treatments correctly.
In this regard, this 2022 the updated version of the guide was presented. Within its content it includes the Contraindications of medicines against Covid-19 that have been approved for emergency use by the Federal Commission for the Protection against Sanitary Risks (Cofepris). Therefore, it is extremely valuable information for your clinical practice.
Nirmatrelvir is an orally bioavailable protease inhibitor that has activity against a viral protease that plays an essential role in virus replication and has demonstrated antiviral activity against coronaviruses. Ritonavir is an inhibitor of cytochrome 5 P450 (CYP) 3A, as well as a pharmacokinetic enhancing agent, which is required to increase nirmatrelvir concentrations to target therapeutic ranges.
Recommendation
• For outpatients with mild to moderate COVID-19 who are at high risk of disease progression.
• Paxlovid (nirmatrelvir 300 mg with ritonavir 100 mg) orally twice daily for 5 days.
• Started as soon as possible and within 5 days after the onset of symptoms in people older than 12 years and weighing more than 40 kg.
• Because Paxlovid has significant and complex drug interactions, primarily due to the presence of ritonavir, physicians should carefully review a patient’s concomitant medications, including over-the-counter medications and herbal supplements, before prescribing, to assess possible drug interactions. drug interactions.
• In patients with kidney failure, with Glomerular Filtration Rate (GFR) between 30-60 ml/min/1.73m2, lower the dose to 150-100 every 12 hours and it is not recommended with GFR less than 30 ml/min/1.73m2. .
• Paxlovid (nirmatrelvir / ritonavir) has not shown benefit in critically ill patients.
NOTE: It is not authorized for the initiation of treatment in patients requiring hospitalization due to severe or critical COVID-19, nor for pre-exposure or post-exposure prophylaxis for the prevention of COVID-19, nor for use for more than 5 consecutive days.
Contraindications
• Hypersensitivity, severe liver or kidney failure. Administration with drugs that are dependent on CYP3A for clearance and whose elevated plasma concentrations are associated with serious and/or fatal reactions. Administration with medicinal products that are strong inducers of CYP3A in which significantly reduced plasma concentrations may be associated with loss of virologic response and resistance. GFR <30ml/min/1.73m2sc
Remdesivir
Inhibitor of viral replication of ribonucleic acid (RNA) viruses.
Outpatient Recommendation
● In non-hospitalized patients with mild to moderate COVID-19 who are at high risk of disease progression.
● If feasible, 3 days of remdesivir (200 mg on day 1 and 100 mg on days 2 and 3).
● In the first 5 days of onset of symptoms.
● Centers with the capacity to administer outpatient intravenous treatment
Demonstrated Benefits in Outpatients
• A randomized controlled clinical trial found that treatment with remdesivir for 3 days in outpatients reduced COVID-19-related hospitalizations (RR: 0.28; 95% CI: 0.1, 0.75). This represents 45 fewer hospitalizations per 1,000 people treated. Although the certainty of the evidence is low, the effect of the drug was strong.
Proven benefits in hospitalized patients
According to a meta-analysis1 by the United Kingdom’s National Institute for Health and Care Excellence, of 4 studies with moderate-quality evidence, they found that remdesivir reduces death by day 28 in hospitalized people who do not require oxygen or who require low-flow oxygen. compared to standard care, but the estimate is not statistically significant (25 fewer deaths per 1,000 people treated [RR 0,72; IC del 95%: 0,52 a 1,01; 6318 personas en 4 estudios])
In hospital use:
It is proposed to change from 5 days to: for a maximum of 5 days or upon discharge if it occurs before this time.
Molnupiravir
Oral prodrug of beta-D-N4-hydroxycytidine (NHC), a ribonucleoside that has antiviral activity against RNA viruses.
Recommendation
• For outpatients with mild to moderate COVID-19 who are at high risk of disease progression.
• 800 mg orally twice a day for 5 days, started as soon as possible and within 5 days of symptom onset, in those over 18 years of age.
• Its use in pregnant patients is not recommended due to data related to fetal toxicity observed during animal studies.
• Molnupiravir has not shown benefit in critically ill patients.
Proven Benefits
• In the interim analysis of the MOVe-OUT study, the absolute risk reduction for hospitalization or death was 3.0% (95% CI: a 0.1, 5.9; p=0.0218) and the reduction relative risk was 30% (RR 0.70; 95% CI: 0.49 to 0.99). Overall, there were 9/699 (1.2%) deaths in the placebo group and 1/709 (0.14%) in the molnupiravir group.
• 11 fewer deaths per 1,000 people treated.
NOTE
• Advise patients of childbearing potential to abstain from sexual intercourse or use reliable contraception during therapy and for up to 4 days after receiving molnupiravir. Reproductive toxicity has been reported in animal studies of molnupiravir, and molnupiravir may be mutagenic during pregnancy.
• Advise men of childbearing potential who are sexually active with women of childbearing potential to abstain from sexual intercourse or use reliable contraception for the duration of treatment and for at least 3 months after the last dose of molnupiravir.
• Recommend not feeding an infant breast milk during treatment with molnupiravir and for 4 days after the final dose. Expressing and discarding breast milk is recommended to maintain the supply during this time.
•Molnupiravir is not licensed for use in children under 18 years of age due to potential effects on bone and cartilage growth.
Contraindications
Hypersensitivity to the drug or components, pregnancy, lactation, under 18 years of age, patients with renal and hepatic insufficiency. Not recommended in fertile women unless using effective contraception
Sotrovimab
Anti-SARS-CoV-2 neutralizing monoclonal antibody,
Recommendation
• Recommended in mild to moderate Covid-19 who are at risk of progression to severe illness, hospitalization, or death.
• 500 mg, single intravenous infusion, administered as soon as possible and within 10 days of onset of symptoms, in those over 12 years of age and weighing over 40 kg.
• Sotrovimab should be administered in a hospital setting as patients should be monitored during the infusion and for at least one hour afterwards, in case serious hypersensitivity reactions occur.
• No benefit has been seen in patients hospitalized for COVID-19. It has been described that monoclonal antibodies against SARS-CoV-2 may be associated with clinical worsening when used in hospitalized patients requiring high-flow oxygen or mechanical ventilation.
Proven Benefits
• In clinical trials for this anti-SARS-CoV-2 monoclonal antibody, they showed a 70% to 85% reduction in the risk of hospitalization or death compared to placebo.
NOTE: There are no studies that have evaluated the use of the above drugs in combination, so if it can be used, it should only be one of them.
Fluvoxamine
Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that is approved by the Food and Drug Administration (FDA) for the treatment of obsessive-compulsive disorder and is used for other conditions, including depression. In a murine sepsis model, fluvoxamine was found to bind to the sigma-1 receptor on immune cells resulting in a reduction in cytokine production. In an in vitro study with human endothelial cells and macrophages, fluvoxamine reduced the expression of some inflammatory genes. Clinical studies are underway to establish whether the anti-inflammatory effects of fluvoxamine observed in in vitro studies are clinically relevant in the context of COVID-19.
Recommendation
• There is insufficient evidence for the COVID19 Treatment Guidelines Panel to recommend for or against use is recommended only in clinical trials.
• Three randomized trials have studied the use of fluvoxamine for the treatment of non-hospitalized COVID-19 patients.
• STOP COVID, a non-contact, double-blind, randomized, placebo-controlled study conducted in the United States in non-hospitalized adults with a mild diagnosis of COVID-19 who received within the first 7 days of symptom onset fluvoxamine (100 mg up to 3 times a day for 15 days) a reduction in clinical deterioration was seen, at day 15.3. Clinical deterioration was defined as shortness of breath plus oxygen saturation (SpO2) <92% or hospitalization plus SpO2 <92%. This was a small study (≤80 participants per arm) with limited cases of clinical deterioration and a short follow-up period. In addition, 24% of the participants stopped responding to the surveys before day 15.
• Subsequently, STOP COVID 2, a phase 3 randomized controlled trial that enrolled >700 participants in the United States and Canada, was halted by a data safety monitoring board after case rates and effects were recorded. treatment lower than expected.
• TOGETHER platform, randomized double-blind placebo-controlled trial conducted in Brazil. Nonhospitalized adults with COVID-19 and a known risk factor for progression to severe disease were randomized to fluvoxamine 100 mg twice daily (n = 741) or placebo (n = 756) for 10 days.
Fluvoxamine use was associated with a lower risk of the primary outcome of retention in the emergency department for >6 hours or admission to hospital. No differences were found in hospitalizations, symptom resolution time, or mortality.
o Participants in the fluvoxamine arm were reported to be less likely to present to an emergency room for COVID-19 in a secondary analysis, although this analysis was not prespecified.
o Its use is recommended exclusively in controlled clinical studies.
Finally, if you are interested in reviewing the complete guide with all the contraindications of the drugs against Covid-19, you can consult here.