Paxlovid

/ Pfizer

The recommended dosage is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) all taken together orally every 12 hours for 5 days. Should be administered as soon as possible after a diagnosis of COVID-19 has been made and within 5 days of symptom onset. 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.
If the patient misses a dose within 8 hours of the time it is usually taken, the patient should take it as soon as possible and resume the normal dosing schedule. If the patient misses a dose by more than 8 hours, the patient should not take the missed dose and instead take the next dose at the regularly scheduled time. The patient should not double the dose to make up for a missed dose.
Special populations
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 should be reduced to nirmatrelvir/ritonavir 150 mg/100 mg every 12 hours for 5 days to avoid over-exposure (this dose adjustment has not been clinically tested). Should not be used in patients with severe renal impairment [eGFR < 30 mL/min, including patients with End Stage Renal Disease (ESRD) under haemodialysis].
Hepatic impairment: No dose adjustment is needed for patients with either mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. This medical product should not be used in patients with severe (Child-Pugh Class C) hepatic impairment.
Concomitant therapy with ritonavir- or cobicistat-containing regimen
No dose adjustment is needed. Patients diagnosed with human immunodeficiency virus (HIV) or hepatitis C virus (HCV) infection who are receiving ritonavir- or cobicistat-containing regimen should continue their treatment as indicated.
See prescribing information for full details.

Treatment of confirmed coronavirus disease 2019 (COVID-19) in adults
who do not require supplemental oxygen and who are at increased risk for progressing to severe COVID-19

* Hypersensitivity to the active substances or to any of the excipients
* Medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening reactions. (alfuzosin, ranolazine, dronedarone, propafenone, quinidine, neratinib, venetoclax, colchicine, terfenadine, lurasidone, pimozide, quetiapine, silodosin, eplerenone, ivabradine, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, voclosporin, lovastatin, simvastatin, lomitapide, eletriptan, finerenone, cariprazine, naloxegol, avanafil, sildenafil, tadalafil, vardenafil, clorazepate, diazepam, estazolam, flurazepam, oral midazolam, triazolam, tolvaptan).
* 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. Treatment cannot be started immediately after discontinuation of CYP3A4 inducers due to the delayed offset of the recently discontinued CYP3A4 inducer. (rifampicin, rifapentine, apalutamide, enzalutamide, carbamazepine, phenobarbital, phenytoin, primidone, lumacaftor/ivacaftor, St. John’s wort (Hypericum perforatum)).

Risk of serious adverse reactions due to interactions with other medicinal products
Management of drug-drug interactions (DDIs) in high-risk COVID-19 patients receiving multiple concomitant medications can be complex and require a thorough understanding of the nature and magnitude of interaction with all concomitant medications. In certain patients, a multi-disciplinary approach (e.g., involving physicians and specialists in clinical pharmacology) should be considered for management of DDIs especially if concomitant medications are withheld, their dosage is reduced, or if monitoring of side effects is necessary.
Effects of Paxlovid on other medicinal products
Initiation of this medical product, a CYP3A inhibitor, in patients receiving medicinal products metabolised by CYP3A or initiation of medicinal products metabolised by CYP3A in patients already receiving this medical product, may increase plasma concentrations of medicinal products metabolised by CYP3A.
Coadministration of Paxlovid with calcineurin inhibitors and mTOR inhibitors
closely and regularly monitoring immunosuppressant blood concentrations and adjusting the dose of the immunosuppressant.
Effects of other medicinal products on Paxlovid
Initiation of medicinal products that inhibit or induce CYP3A may increase or decrease concentrations of nirmatrelvir/ritonavir, respectively.
These interactions may lead to:
* Clinically significant adverse reactions, with severe, life-threatening or fatal events from
greater exposures of concomitant medicinal products.
* Clinically significant adverse reactions from greater exposures of this medical product.
* Loss of therapeutic effect of this medical prosuct and possible development of viral resistance.
Hypersensitivity reactions
Anaphylaxis, hypersensitivity reactions and serious skin reactions (including toxic epidermal necrolysis and Stevens-Johnson syndrome) have been reported. If signs
and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue treatment and initiate appropriate medications and/or supportive care.
Severe renal impairment
No clinical data are available in patients with severe renal impairment (including patients with ESRD). Based on pharmacokinetic data, the use of this medical product in patients with severe renal impairment could lead to over-exposure with potential toxicity. No recommendation in terms of dose adjustment could be elaborated at this stage pending dedicated investigation. Therefore, this medical product should not be used in patients with severe renal impairment (eGFR < 30 mL/min, including patients with ESRD under haemodialysis).
Hepatotoxicity
Hepatic transaminase elevations, clinical hepatitis and jaundice have occurred in patients receiving ritonavir. Therefore, caution should be exercised when administering to patients with pre-existing liver diseases, liver enzyme abnormalities or hepatitis.
Elevation in blood pressure
Cases of hypertension, generally non serious and transient, have been reported during treatment. Specific attention including regular monitoring of blood pressure should be paid notably to elderly patients since they are at higher risk of experiencing serious complications of hypertension.
Risk of HIV-1 resistance development
Because nirmatrelvir is coadministered with ritonavir, there may be a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection.
See prescribing information for full details.

Common: dysgeusia, diarrhoea, headache and vomiting.
See prescribing information for full details.

Effect of other medicinal products on Paxlovid
Nirmatrelvir and ritonavir are CYP3A substrates.
Coadministration of this medical product with medicinal products that induce CYP3A may decrease nirmatrelvir and ritonavir plasma concentrations and reduce therapeutic effect.
Coadministration with medicinal product that inhibits CYP3A4 may increase nirmatrelvir and ritonavir plasma concentrations.
Effects of Paxlovid on other medicinal products
Medicinal products CYP3A4 substrates
This medical product (nirmatrelvir/ritonavir) is a strong inhibitor of CYP3A and increases plasma concentrations of medicinal products that are primarily metabolised by CYP3A. Thus, coadministration of nirmatrelvir/ritonavir with medicinal products highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated. Coadministration of other CYP3A4 substrates that may lead to potentially significant interaction should be considered only if the benefits outweigh the risks.
Medicinal products CYP2D6 substrates
Based on in vitro studies, ritonavir has a high affinity for several cytochrome P450 (CYP) isoforms and may inhibit oxidation with the following ranked order: CYP3A4 > CYP2D6. Coadministration with drug substrates of CYP2D6 may increase the CYP2D6 substrate concentration.
Medicinal products P-glycoprotein substrates
Interaction with P-glycoprotein (P-gp) is characterized by high affinity and inhibition of this transporter; caution should thus be exercised in case of concomitant treatment. Close drug monitoring for safety and efficacy should be performed, and dose reduction may be adjusted accordingly, or avoid concomitant use.
This medical product may induce glucuronidation and oxidation by CYP1A2, CYP2B6, CYP2C8, CYP2C9 and CYP2C19 thereby increasing the biotransformation of some medicinal products metabolised by these pathways and may result in decreased systemic exposure to such medicinal products, which could decrease or shorten their therapeutic effect.
Based on in vitro studies there is a potential for nirmatrelvir to inhibit MDR1 and OATP1B1 at clinically relevant concentrations.
See prescribing information for full details.

Pregnancy: There are limited data on the use in pregnant women to inform the drug-associated risk of adverse developmental outcomes; women of childbearing potential should avoid becoming pregnant during treatment and as a precautionary measure for 7 days after completing treatment.
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, and until one menstrual cycle after stopping treatment.
A large number of women exposed to ritonavir during pregnancy indicate no increase in the rate of birth defects compared to rates observed in population-based birth defect surveillance systems.
This medical product is not recommended during pregnancy and in women of childbearing potential not using contraception unless the clinical condition requires.
Lactation: Nirmatrelvir and ritonavir are excreted in breast milk. There are no available data on the effects of nirmatrelvir and ritonavir on the breast-fed
newborn/infant or on milk production. A risk to the newborn/infant cannot be excluded.
Breast-feeding should be discontinued during treatment and as a precautionary measure for 48 hours after completing treatment.

Treatment of overdose 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.

30 tablets. Each daily blister card contains 4 nirmatrelvir tablets and 2 ritonavir tablets for morning and evening dose.