Published: 1 December 2022

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Adverse drug reactions reported following use of oral COVID-19 therapeutics in New Zealand

Prescriber Update 43(4): 51–54
December 2022

This article provides an overview of suspected adverse drug reactions (ADRs) to nirmatrelvir + ritonavir (Paxlovid) and molnupiravir (Lagevrio) reported to the Centre for Adverse Reactions Monitoring (CARM).

Paxlovid and Lagevrio are oral antiviral treatments for COVID-19 infection, given provisional approval on 2 March 2022 and 14 April 2022, respectively. 

It is important to report suspected ADRs for these new medicines to CARM so that Medsafe and CARM can closely monitor their safety and identify new safety concerns. Reporting is easiest online.  

Paxlovid

As of 30 September 2022, CARM had received a total of 72 reports where Paxlovid was listed as the suspect or interacting medicine. Table 1 provides an overview of suspected ADRs reported following the use of Paxlovid.

Table 1: Overview of suspected adverse drug reactions following the use of Paxlovid (nirmatrelvir + ritonavir) reported to the Centre for Adverse Reactions Monitoring as of 30 September 2022 (list not exhaustive^a), and relevant data sheet text

Adverse drug reaction	Number of reports	What the Paxlovid data sheet saysb,c
Taste disturbances	17	Dysgeusia: reported as a common adverse event in clinical trials
Diarrhoea	14	Diarrhoea: reported as a common adverse event in clinical trials
Nausea	12	Nausea: identified as an adverse event during post-marketing use of Paxlovid
COVID-19 rebound effect	11	Post-treatment increases in SARS-CoV-2 nasal RNA levels (ie, viral RNA rebound) were observed on day 10 and/or day 14 in a subset of Paxlovid and placebo recipients in clinical trials, irrespective of COVID-19 symptoms.
Vomiting	9	Vomiting: reported as a common adverse event in clinical trials
Hypertension	3	Hypertension: reported as an uncommon adverse event in clinical trials
Jaundice	2	The warnings and precautions/hepatotoxicity section states that jaundice has occurred in patients receiving ritonavir. Caution should be exercised in patients with pre-existing liver diseases, liver enzyme abnormalities or hepatitis.

Notes:

1. Reports can include more than one suspected ADR. Not all reported ADRs are shown in the table.
2. Pfizer New Zealand Limited. 2022. Paxlovid New Zealand Data Sheet 15 September 2022. URL: medsafe.govt.nz/profs/Datasheet/p/paxlovidtab.pdf (accessed 18 October 2022).
3. Frequencies are defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); not known (frequency cannot be estimated from the available data).

Potential drug-drug interactions with Paxlovid

Paxlovid is a cytochrome P450 3A (CYP3A) inhibitor and may increase plasma concentrations of medicines primarily metabolised by this enzyme.¹ Patients taking Paxlovid may be more susceptible to ADRs from their usual medicines if potential drug-drug interactions are not appropriately managed. To minimise the risk of drug-drug interactions:

• refer to the data sheet and other available resources to screen and manage these interactions before prescribing and dispensing Paxlovid
• take an up-to-date medication history, including regular prescription medicines, medicines taken as needed, over-the-counter (OTC) medicines and any herbal products
• advise patients taking Paxlovid to check with their healthcare professional before starting any new medicines (prescription or OTC) and herbal products.

Table 2 lists some medicines and herbal products contraindicated for concomitant use with Paxlovid.

Table 2: Medicines and herbal products that are contraindicated for concomitant use with Paxlovid* (nirmatrelvir + ritonavir)

Interactions that result in an increase or decrease in concentrations of concomitant medicine and are associated with serious and/or life-threatening reactions
Medicinal product class	Medicinal products within the class
Antianginal	Ranolazine
Antiarrhythmics	Amiodarone, flecainide, propafenone
Antibiotic	Fusidic acid
Anticancer	Neratinib, venetoclax
Anti-gout	Colchicine
Antipsychotics	Clozapine
Ergot derivatives	Ergometrine
HMG-CoA reductase inhibitors	Simvastatin
Opioid analgesic	Pethidine
PDE5 inhibitor	Avanafil, sildenafil, vardenafil, tadalafil
Sedative/hypnotics	Diazepam, triazolam
Interactions that result in a decrease in Paxlovid concentrations and are associated with loss of virologic response and possible resistance
Product class	Products within the class
Anticancer	Apalutamide
Anticonvulsant	Carbamazepine, phenobarbital, phenytoin
Antimycobacterials	Rifampicin
Herbal products	St. John’s Wort (Hypericum perforatum)

* Medicines listed in this table are a guide and are not considered a comprehensive list of all possible medicines that may be contraindicated with Paxlovid.
Source: Pfizer New Zealand Limited. 2022. Paxlovid New Zealand Data Sheet 15 September 2022. URL: medsafe.govt.nz/profs/Datasheet/p/paxlovidtab.pdf (accessed 18 October 2022).

Lagevrio

As of 30 September 2022, CARM had received a total of 11 reports where Lagevrio was listed as the suspect medicine. Table 3 provides an overview of suspected ADRs reported following the use of Lagevrio.

Table 3: Overview of suspected adverse drug reactions following the use of Lagevrio (molnupiravir) reported to the Centre for Adverse Reactions Monitoring as of 30 September 2022 (list not exhaustive^a), and relevant data sheet text 

Adverse drug reaction	Number of reports	What the Lagevrio data sheet saysb
Skin reactions	6	Erythema, rash and urticaria: identified as adverse reactions during post-marketing use of Lagevrio
Nausea	2	Nausea: reported in 1% of participants taking Lagevrio and placebo in clinical trials
Vomiting	2	Vomiting: reported in 1% of participants taking Lagevrio and placebo in clinical trials
Diarrhoea	2	Diarrhoea: reported in 2% of participants taking Lagevrio and placebo in clinical trials

Notes:

1. Reports can include more than one suspected ADR. Not all reported ADRs are shown in the table.
2. Merck Sharp & Dohme (New Zealand) Limited. 2022. Lagevrio New Zealand Data Sheet 14 April 2022. URL: medsafe.govt.nz/profs/datasheet/l/lagevirocap.pdf (accessed 18 October 2022).

More information

• How Medsafe monitors the safety of medicines
• See the medicine’s data sheet and Consumer Medicine Information for the known side effects
• Search the Suspected Medicine Adverse Reaction Search (SMARS) database for reports of suspected adverse drug reactions to medicines
• Ministry of Health: COVID-19: Advice for all health professionals

Reference

1. Pfizer New Zealand Limited. 2022. Paxlovid New Zealand Data Sheet. 15 September 2022. URL: medsafe.govt.nz/profs/Datasheet/p/paxlovidtab.pdf (accessed 18 October 2022).