nirmatrelvir + ritonavir: clinical use

Prescribing considerations

• Confirm the licensed clinical context and assess renal and hepatic function before prescribing.
• Obtain a complete history of prescribed, pharmacy, herbal and recreational substances and check the current product-specific interaction tables.
• Renal impairment changes the required pack instructions; ensure the patient understands exactly which supplied tablets are required.
• Use particular caution with pre-existing liver disease, liver enzyme abnormalities or hepatitis.
• Consider the potential for HIV-1 protease-inhibitor resistance in uncontrolled or undiagnosed HIV infection.

Contraindications and cautions

• Clinically significant hypersensitivity to nirmatrelvir, ritonavir or an excipient.
• Severe hepatic impairment.
• Medicines highly dependent on CYP3A clearance where increased exposure can cause serious or life-threatening harm.
• Potent CYP3A inducers that may substantially reduce antiviral exposure and cause loss of response or resistance.

Monitoring

• Renal and hepatic function as clinically appropriate.
• Toxicity or reduced effectiveness of interacting medicines during and after treatment where relevant.
• Blood concentrations of calcineurin or mTOR inhibitors if specialist-led coadministration is unavoidable.
• Signs of hypersensitivity, serious skin reactions or hepatotoxicity.
• Thyroid function when clinically relevant in people taking levothyroxine.

Clinical pharmacology

Nirmatrelvir inhibits the SARS-CoV-2 main protease. Ritonavir inhibits CYP3A metabolism of nirmatrelvir and acts as a pharmacokinetic enhancer; it also creates extensive interaction potential through effects on CYP enzymes and transporters.

Formulation and product differences

• The product contains separate co-packaged tablets: pink, oval nirmatrelvir tablets and white to off-white, capsule-shaped ritonavir tablets.
• The nirmatrelvir tablets contain lactose.
• Pack contents may exceed what is required for people with impaired renal function, making clear individualised dispensing instructions important.

Tablet

Route: Oral

Strengths: 150 mg + 100 mg