COVID-19 Notes
By Dr. Satish K Gupta*
Molnupiravir
The Subject Expert Committee (SEC) on COVID-19 of the Central Drugs Standard Control Organisation (CDSCO) on Tuesday December 28, 2021 recommended granting permission to manufacture and market anti-Covid pill Molnupiravir for restricted emergency use for the treatment of adult patients.
All the recommendations have been sent to the Drugs Controller General of India (DCGI) for final approval.
Will it available for On the Counter Sale?
No, The pill will be sold by retail only under the prescription of medical doctors.
Mechanism of action?
Molnupiravir is an orally administered form of ribonucleoside that prevents the replication of SARS-CoV-2, which causes Covid-19. It forces SARS-CoV-2 to try to replicate its genetic material. However, as the process begins, the pill inserts errors into the genetic code of replicating virus.
When to give it?
Molnupiravir should be administered as soon as possible after a diagnosis of COVID-19, and within five days of symptom onset.
Is it recommended for indoor serious patients?
No, drug is to be used in OPD basis. Because drug hampers viral replication which occurs early after infection. Later effects of Covid-19 are driven by inflammation. Drug has no anti inflammatory activity.
Do we need to give Paracetamol along with drug?
Yes, for deffervescence one may need to give other drugs. Other symptoms of Covid-19 may require additional therapies.
Will it be effective in patients of low Oxygen?
No, Use Oxygen Prone ventilation.
What does Molnupiravir do?
It is stated to prevent progression of disease leading to hospitalization.
Whom should it be given?
Adult Covid-19 patients with Comorbidities like Diabetes, CKD, COPD Heart Disease, COPD, immunocompromised states, Obesity within 5 days of symptom onset .
Will it work against Omicron?
Yes, mechanism of drug is independent of spike protein mutation.
Efficacy?
Phase-III clinical trial showed that the pill was able to reduce the risk of hospitalisation or death in half.
Later in final analysis company clarified that Molnupiravir reduces hospitalisation or death by 30%. The drug’s efficacy is considerably lower than what was reported in interim analysis in October, when Molnupiravir was said to reduce the risk of hospitalisation and death by around 50%.
Dose?
Overall, the course has 40 pills. 800 mg (four 200 mg capsules) taken orally every 12 hours for five days, with or without food. Completion of the full five-day treatment course is important to maximize viral clearance and minimize transmission of SARS-CoV-2. Once started complete the course.
Side effects?
The most common adverse reactions for Molnupiravir were
- Diarrhea (2%)
- Nausea (1%)
- Headache and
- Dizziness (1%)
Drug interactions?
Nil.
The drug is not authorised
- for use in patients less than 18 years of age
- or for longer than five consecutive days
- and for pre-exposure or post-exposure prophylaxis for prevention of COVID-19
- for pregnant women.
- for initiation of treatment in patients hospitalized due to COVID-19.
Contraindications
Molnupiravir is not recommended for use in patients who are pregnant. Based on findings from animal reproduction studies, Molnupiravir may cause fetal harm when administered to pregnant individuals. No human data.
Avoid pregnancy for 4 days after the last dose
Females of childbearing potential should use a reliable method of contraception correctly and consistently, as applicable, for the duration of treatment and for four days after the last dose of Molnupiravir.
Lactational mothers
No details known but based on the potential for adverse reactions in the infant from molnupiravir, breastfeeding is not recommended during treatment with molnupiravir and for 4 days after the final dose. A lactating individual may consider interrupting breastfeeding and may consider pumping and discarding breast milk during treatment and for 4 days after the last dose of molnupiravir.
Males watch out!
Males of reproductive potential who are sexually active with females of childbearing potential should use a reliable method of contraception correctly and consistently during treatment and for at least three months after the last dose.
Who invented the drug?
Invented at a not-for-profit biotechnology company, Drug Innovations at Emory (DRIVE), it has been developed by Merck in collaboration with Ridgeback Biotherapeutics.
Who will manufacture the drug in India?
An anti-viral drug, it will be manufactured in India by 13 companies for restricted use under emergency situations for treatment of adult patients with Covid-19 and who have a high risk of progression of the disease. *Dr Reddy’s Laboratories, in consortium with Cipla, Mylan, Torrent, Emcure and Sun pharma* had presented their proposal for approval of Molnupiravir 200mg capsules for approval in the emergency situation along with various supporting documents.
Risk of Mutagenesis in Sars CoV -2
Molnupiravir is a broad-spectrum antiviral that is an orally bioavailable prodrug of the nucleoside analogue β-D-N4-hydroxycytidine (NHC). Molnupiravir or NHC can increase G to A and C to U transition mutations in replicating coronaviruses.
However, Molnupiravir’s ability to introduce mutations to the virus itself that are significant enough to change how the virus functions, but not so powerful as to stop it from replicating and becoming the next dominant variant.
While it’s possible that at the optimal concentration, the drug may very well cause enough mutations to prevent replication and onward transmission of the virus, the impact of suboptimal doses is still very much unknown. The current protocol for the use of molnupiravir is an 800mg dose, given as pills, twice a day for five days. At that concentration, molnupiravir would theoretically take no prisoners, leaving not a single viral genome to escape unscathed.
But there is a strong likelihood that in the real world, people will not take the full course of pills. A slew of studies on adherence to daily oral antibiotics suggest that many patients — as many as 40% — fail to complete the full course of treatment. At these suboptimal concentrations, Molnupiravir could have the unfortunate effect of introducing mutations across every gene and protein of the virus, including the spike, but not necessarily killing it off. But such effects not seen till now in clinical trials
Overall place in treatment of Covid-19
Not a wonder Drug!
Likely to have limited role in high risk patients if given early in course of disease. No symptom relief but stated to prevent hospitalization in 30% cases. Effective monoclonal antibodies have much better place. Useful pending advent of a better drug
Watch Out
Follow Covid Appropriate Behaviour.
*Dr. Satish K Gupta is an MD in Medicines, a Visiting Senior Consultant Physician and Internist at Max Super Speciality Hospital, and a Clinical Assistant Professor at GS Medical College, Chaudhary Charan Singh University, Meerut. He is the author of Journey of COVID in India: A Doctor’s Perspective
