This medicinal product has been authorised under a so-called 'conditional approval' scheme. This means that further evidence on this medicinal product is awaited. The European Medicines Agency will review new information on this medicinal product at least every year, and this Summary of Product Characteristics (SmPC) will be updated as necessary.

PAXLOVID is indicated for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk for progressing to severe COVID-19.

For more information about who is at increased risk for progressing to severe COVID-19, see Section 5.1: Paxlovid Malaysia Prescribing Information: [here].

The following are risk factors for progression to severe disease²:

• 60 years of age and older, regardless of comorbidities 
• Overweight (BMI >25)
• Current smoker
• Chronic kidney disease
• Diabetes
• Immunosuppressive disease or immunosuppressive treatment
• Cardiovascular disease
• Sickle cell disease
• Hypertension
• Chronic lung disease (including asthma)
• Neurodevelopmental disorders
• Active cancer
• Medically related technological dependence 

Other medical conditions or factors may also place individual patients at high risk for progressing to severe COVID-19. Please refer to the CDC guidelines <CDC link> for a comprehensive list of high risk factors. Healthcare providers should consider the benefits and risks for each individual patient.

For more information about risk factors for progression to severe disease, see Section 5.1: Paxlovid Malaysia Prescribing Information: [here]. 

PAXLOVID has been granted a CMA for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk for progressing to severe disease.
​​​​​​​
PAXLOVID is not authorised for use in paediatric patients. The safety and efficacy of PAXLOVID in patients below 18 years of age have not been established. No data are available.

For oral use.

Nirmatrelvir must be coadministered with ritonavir. Failure to correctly coadminister nirmatrelvir with ritonavir will result in plasma levels of this active substance that will be insufficient to achieve the desired therapeutic effect. PAXLOVID can be taken with or without food. The tablets should be swallowed whole and not chewed, broken, or crushed. 
 
For more information, see Section 5.1: Paxlovid Malaysia Prescribing Information: [here]. 

Nirmatrelvir is a peptidomimetic inhibitor of the SARS-CoV-2 main protease (M^pro), also known as 3-chymotrypsin-like cysteine (3CL) protease enzyme. Inhibition of the SARS-CoV-2 M^pro renders the protein incapable of processing polyprotein precursors, which leads to the prevention of viral replication. 

Ritonavir inhibits the CYP3A-mediated metabolism of nirmatrelvir, thereby providing increased plasma concentrations of nirmatrelvir.

For more information about how PAXLOVID works and its antiviral activity, see Section 5.1: Pharmacodynamic properties of the SmPC [here]. 

Ritonavir is administered with nirmatrelvir as a pharmacokinetic enhancer resulting in higher systemic concentrations of nirmatrelvir. Upon repeat-dose of nirmatrelvir/ritonavir 75 mg/100 mg, 250 mg/100 mg, and 500 mg/100 mg administered twice daily, the increase in systemic exposure at steady-state appears to be less than dose proportional. Multiple dosing over 10 days achieved steady-state on Day 2 with approximately two-fold accumulation. Systemic exposures on Day 5 were similar to Day 10 across all doses.

For more information about ritonavir, see Section 5.2: Pharmacokinetic properties of the SmPC [here].

The efficacy of PAXLOVID is based on the interim analysis and the supporting final analysis of EPIC-HR, a phase 2/3, randomised, double-blind, placebo-controlled study in nonhospitalised, symptomatic adult participants with a laboratory-confirmed diagnosis of SARS-CoV-2 infection. Eligible participants were 18 years of age and older with at least 1 identified risk factor for progression to severe disease: diabetes, overweight (BMI >25), chronic lung disease (including asthma), chronic kidney disease, current smoker, immunosuppressive disease or immunosuppressive treatment, cardiovascular disease, hypertension, sickle cell disease, neurodevelopmental disorders, active cancer, medically related technological dependence, or were 60 years of age and older, regardless of comorbidities. Participants with COVID-19 symptom onset of ≤5 days were included in the study. The study excluded individuals with a history of prior COVID-19 infection or vaccination.

Participants were randomised (1:1) to receive PAXLOVID (nirmatrelvir 300 mg/ritonavir 100 mg) or placebo orally every 12 hours for 5 days. The primary efficacy endpoint was the proportion of participants with COVID-19–related hospitalisation or death from any cause through Day 28. The analysis was conducted in the modified intent-to-treat (mITT) analysis set [all treated subjects with onset of symptoms ≤3 days who at baseline did not receive nor were expected to receive COVID-19 therapeutic monoclonal antibody (mAb) treatment], the mITT1 analysis set (all treated subjects with onset of symptoms ≤5 days who at baseline did not receive nor were expected to receive COVID-19 therapeutic mAb treatment), and the mITT2 analysis set (all treated subjects with onset of symptoms ≤5 days). 

A total of 2246 participants were randomised to receive either PAXLOVID or placebo. At baseline, mean age was 46 years with 13% of participants 65 years of age and older (3% were 75 years of age and older); 51% were male; 72% were White, 5% were Black, and 14% were Asian; 45% were Hispanic or Latino; 66% of participants had onset of symptoms ≤3 days from initiation of study treatment; 81% had a BMI ≥25 kg/m² (37% a BMI ≥30 kg/m²); 12% had diabetes mellitus; 47% of participants were serological negative at baseline and 51% were serological positive. The mean (SD) baseline viral load was 4.63 log₁₀ copies/mL (2.87); 26% of participants had a baseline viral load of >10⁷ (copies/mL); 6.2% of participants either received or were expected to receive COVID-19 therapeutic mAb treatment at the time of randomisation and were excluded from the mITT and mITT1 analyses. The primary SARS-CoV-2 variant across both treatment arms was Delta (98%), mostly clade 21J (based on interim analysis). 

The baseline demographic and disease characteristics were balanced between the PAXLOVID and placebo groups. 

The determination of primary efficacy was based on a planned interim analysis of 774 subjects in the mITT population. The estimated risk reduction was -6.3% with an unadjusted 95% CI of (-9.0%, -3.6%) and a 95% CI of (-10.61%, -2.02%) when adjusting for multiplicity. The two-sided P value was <0.0001 with 2-sided significance level of 0.002. 

Table 1 provides results of the primary endpoint in the mITT1 analysis population for the full data set at final study completion. 

The safety of PAXLOVID is based on data from EPIC-HR, a phase 2/3, randomised, double-blind, placebo-controlled trial in nonhospitalised, symptomatic adult participants with a laboratory-confirmed diagnosis of SARS-CoV-2 infection.

The most common adverse reactions reported during treatment with PAXLOVID (nirmatrelvir/ritonavir 300 mg/100 mg) every 12 hours for 5 days and during 34 days after the last dose were dysgeusia (5.6%), diarrhoea (3.1%), headache (1.4%), and vomiting (1.1%). 

For more information about adverse reactions, see Section 4.8: Undesirable effects of the SmPC [here]. 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V of the SmPC [here]. [Countries to insert information.]

For more information about adverse reactions, see Section 4.8: Undesirable effects of the SmPC [here].

Report suspected adverse reactions directly to [GLocal URL]. 

The recommended dosage in adult patients is 300 mg nirmatrelvir (two tablets) with 100 mg ritonavir (one tablet), all taken together orally every 12 hours for 5 days. PAXLOVID should be administered as soon as possible after a diagnosis of COVID-19 has been made and within 5 days of symptom onset. 

Patients take the PAXLOVID treatment course orally, every 12 hours, for 5 days. 
Completion of the full 5-day treatment course is recommended even if the patient requires hospitalisation due to severe or critical COVID-19 after starting treatment with PAXLOVID.

Morning Dose

• Two pink tablets of nirmatrelvir
• One white tablet or ritonavir

Patients should take all 3 tablets together.

Evening Dose

• Two pink tablets of nirmatrelvir
• One white tablet or ritonavir

Patients should take all 3 tablets together.

Dosing for Patients with Renal Impairment
No dose adjustment is needed in patients with mild renal impairment (eGFR ≥60 to <90 mL/min). 

In patients with moderate renal impairment (eGFR ≥30 to <60 mL/min), the dose of PAXLOVID should be reduced to nirmatrelvir/ritonavir 150 mg/100 mg every 12 hours for 5 days to avoid overexposure (this dose adjustment has not been clinically tested). 

PAXLOVID should not be used in patients with severe renal impairment [eGFR <30 mL/min, including patients with End Stage Renal Disease (ESRD) under haemodialysis]. 

Dosing in Patients with Hepatic Impairment
No dose adjustment of PAXLOVID is needed for patients with either mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. PAXLOVID should not be used in patients with severe hepatic impairment.

Nirmatrelvir must be coadministered with ritonavir. Failure to correctly coadminister
Nirmatrelvir with ritonavir will result in plasma levels of this active substance that will be insufficient to achieve the desired therapeutic effect. PAXLOVID can be taken with or without food. The tablets should be swallowed whole and not chewed, broken, or crushed.

PAXLOVID should be administered as soon as possible after a diagnosis of COVID-19 has been made and within 5 days of symptom onset.

For more information about dosage, see Section 4.2: Posology and method of administration of the SmPC [here].

There are no data on the use of PAXLOVID in pregnant women to inform the drug-associated risk of adverse developmental outcomes; as a precautionary measure, women of childbearing potential should avoid becoming pregnant during treatment with PAXLOVID and for 7 days after completing PAXLOVID. 

Use of ritonavir may reduce the efficacy of combined hormonal contraceptives. Patients using combined hormonal contraceptives should be advised to use an effective alternative contraceptive method or an additional barrier method of contraception during treatment with PAXLOVID and until 1 menstrual cycle after stopping PAXLOVID. 

PAXLOVID is not recommended during pregnancy and in women of childbearing potential not using contraception unless the clinical condition requires treatment with PAXLOVID. 

For more information and data from embryo-fetal developmental toxicity studies with nirmatrelvir and ritonavir, see Section 4.6: Fertility, pregnancy, and lactation of the SmPC [here] and Section 5.3: Preclinical safety data [here].

[for countries to fill out]

PAXLOVID film-coated tablets are available in 5 daily-dose blister cards, with a total of 30 tablets packaged in a carton. Each daily blister card contains 4 nirmatrelvir tablets (150 mg each) and 2 ritonavir tablets (100 mg each) and indicates which tablets need to be taken in the morning and evening (sun and moon symbols). 

• Nirmatrelvir film-coated tablets are pink, oval shaped, and debossed with ‘PFE’ on one side and ‘3CL’ on the other side
• Ritonavir film-coated tablets are white to off-white, capsule shaped, and debossed with ‘H’ on one side and ‘R9’ on the other side

For more information, see Section 3: Pharmaceutical form of the SmPC [here].

Instructions for a missed dose:

• If the patient misses a dose of PAXLOVID within 8 hours of the time it is usually taken, advise the patient to take it as soon as possible and resume the normal dosing schedule
• If the patient misses a dose by more than 8 hours, tell them to not take the missed dose and to instead take the next dose at the regularly scheduled time
• The patient should not double the dose to make up for a missed dose 

Instructions for an overdose:

• Treatment of overdose with PAXLOVID should consist of general supportive measures, including monitoring of vital signs and observation of the clinical status of the patient
• There is no specific antidote for overdose with PAXLOVID

For medical questions related to PAXLOVID, you can go to  https://pmiform.com/HCP/MY

PAXLOVID is contraindicated in/with:

• Hypersensitivity to the active substances or to any of the excipients in Section 6.1: List of excipients [here]
• Medicinal products that are highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions
• Medicinal products that are potent CYP3A inducers where significantly reduced nirmatrelvir/ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance

For a list of potential clinically significant drug interactions, including contraindicated drugs, refer to Section 4.3: Contraindications [here] and Section 4.5: Interaction with other medicinal products and other forms of interaction, Table 1: Interaction with other medicinal products and other forms of interaction [here].

PAXLOVID (nirmatrelvir/ritonavir) is an inhibitor of CYP3A and may increase plasma concentrations of medicinal products that are primarily metabolised by CYP3A. Medicinal products that are extensively metabolised by CYP3A and have high first-pass metabolism appear to be the most susceptible to large increases in exposure when coadministered with nirmatrelvir/ritonavir. Thus, coadministration of nirmatrelvir/ritonavir with medicinal products highly dependent of CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated.

Initiation of PAXLOVID, a CYP3A inhibitor, in patients receiving medicinal products metabolised by CYP3A or initiation of medicinal products metabolised by CYP3A in patients already receiving PAXLOVID, may increase plasma concentrations of medicinal products metabolised by CYP3A. 

Initiation of medicinal products that inhibit or induce CYP3A may increase or decrease concentrations of PAXLOVID, respectively. These interactions may lead to:

• Clinically significant adverse reactions, potentially leading to severe, life-threatening, or fatal events from greater exposures of concomitant medicinal products
• Clinically significant adverse reactions from greater exposures of PAXLOVID 
• Loss of therapeutic effect of PAXLOVID and possible development of viral resistance

As a conservative measure, the drug-drug interactions pertaining to ritonavir used in chronic HIV infection (600 mg BID when originally used as an antiretroviral agent and 100 mg BID as currently used as a pharmacokinetic enhancer with antiretroviral agents) should apply for PAXLOVID. Future investigations may enable an adjustment of the recommendations related to drug-drug interactions to the 5-day treatment duration of PAXLOVID.

For a list of potential clinically significant drug interactions, including contraindicated drugs, refer to Section 4.5: Interaction with other medicinal products and other forms of interaction, Table 1: Interaction with other medicinal products and other forms of interaction [here].

Authentic PAXLOVID™ from Pfizer will include the Pfizer name on the outer carton and will be packaged in 5 aluminium push-through blister cards. To ensure that the tablets are legitimate, look for specific text debossed on each side of the tablets. nirmatrelvir tablets are pink, oval shaped, and debossed with ‘PFE’ on one side and ‘3CL’ on the other side.​ Ritonavir tablets are white to off-white, capsule shaped, and debossed with ‘H’ on one side and ‘R9’ on the other side.  

The outer carton has a colourless, glossy coating that contains a repeated pattern of the Pfizer name and logo all over. The Pfizer name and logo appear in a contrasting matte finish.

[Patients with moderate renal impairment will receive a carton that has been opened and modified by the pharmacist to indicate a dose adjustment. To view PAXLOVID dispensing information for patients with moderate renal impairment, see the pharmacist instruction sheet and the Letter to Healthcare Providers (Dec. 2021)].

See more information about product authenticity [here].