RINVOQ

Clinical safety rating: caution

Comprehensive clinical and safety monograph for RINVOQ (RINVOQ).

How it works

Janus kinase (JAK) inhibitor; selectively inhibits JAK1 and JAK2, modulating the JAK-STAT signaling pathway involved in cytokine-mediated inflammation and immune responses.

What the body does with it

Metabolism	Primarily metabolized by cytochrome P450 (CYP) 3A4; minor contribution from CYP2D6.
Excretion	UpToDate: 24% renal (as unchanged drug), 52% fecal (as metabolites); Clinical Pharmacology: 24% renal (unchanged), 52% fecal (metabolites), <1% biliary
Half-life	Terminal elimination half-life: 6.5–8.9 hours (mean ~7 hours) in healthy subjects; in patients with rheumatoid arthritis, similar half-life supports twice-daily dosing
Protein binding	~52% bound, primarily to albumin and α1-acid glycoprotein
Volume of Distribution	Volume of distribution: 97–101 L (approx 1.2–1.5 L/kg indicating extensive extravascular distribution); suggests distribution into tissues
Bioavailability	Oral bioavailability: ~75% (with high-fat meal increases exposure by 20–25%, clinical effect minimal; take with or without food)
Onset of Action	Oral: clinical improvement observed within 1–2 weeks for rheumatoid arthritis; for ulcerative colitis, response seen as early as 2 weeks
Duration of Action	Sustained response with continued twice-daily dosing; loss of effect may occur within weeks of discontinuation; not intended for intermittent use

Classification & Brands

Dosing & administration

15 mg orally once daily, with or without food.

Dosage form	TABLET, EXTENDED RELEASE
Renal impairment	No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min). Not recommended in severe renal impairment (eGFR <30 mL/min).
Liver impairment	No dose adjustment in mild hepatic impairment (Child-Pugh A). Not recommended in moderate or severe hepatic impairment (Child-Pugh B or C).
Pediatric use	Approved for pediatric patients 12 years and older with polyarticular juvenile idiopathic arthritis or psoriatic arthritis: 15 mg orally once daily. For atopic dermatitis: pediatric patients 12-17 years, 15 mg orally once daily.
Geriatric use	No specific dose adjustment required; however, due to higher risk of infections and thrombotic events in elderly patients, use with caution. No pharmacokinetic differences observed in patients over 65 years.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for RINVOQ (RINVOQ).

Breastfeeding	No data on presence in human milk; upadacitinib is detected in rat milk. M/P ratio unknown. Breastfeeding is not recommended during therapy and for 6 days after last dose.
Teratogenic Risk	Upadacitinib is an immunomodulator; animal studies show fetal toxicity including skeletal malformations at exposures below human exposure. In humans, limited data; use is contraindicated during pregnancy. Increased risk of congenital malformations cannot be excluded, particularly in first trimester.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Serious infections: increased risk of bacterial, mycobacterial, invasive fungal, viral, or other opportunistic infections, leading to hospitalization or death. Malignancies: lymphoma and other malignancies reported. Thrombosis: deep vein thrombosis, pulmonary embolism, and arterial thrombosis. All-cause mortality: higher rate in RA patients ≥50 years with at least one cardiovascular risk factor.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to upadacitinib or excipients; active serious infections, including localized infections; active TB; severe hepatic impairment (Child-Pugh C).

Clinical Precautions

Precautions

Serious infections; tuberculosis (screen and treat prior to therapy); viral reactivation (herpes zoster, HBV, HCV); thrombosis; malignancy; major adverse cardiovascular events (MACE); gastrointestinal perforation; anemia, leukopenia, neutropenia, lymphopenia; lipid elevations; elevated liver enzymes; vaccination avoidance (live vaccines); hypersensitivity reactions.

Clinical Tips & Counseling

Drug interactions

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RINVOQ

Clinical safety rating: caution

Comprehensive clinical and safety monograph for RINVOQ (RINVOQ).

How it works

Janus kinase (JAK) inhibitor; selectively inhibits JAK1 and JAK2, modulating the JAK-STAT signaling pathway involved in cytokine-mediated inflammation and immune responses.

What the body does with it

Metabolism	Primarily metabolized by cytochrome P450 (CYP) 3A4; minor contribution from CYP2D6.
Excretion	UpToDate: 24% renal (as unchanged drug), 52% fecal (as metabolites); Clinical Pharmacology: 24% renal (unchanged), 52% fecal (metabolites), <1% biliary
Half-life	Terminal elimination half-life: 6.5–8.9 hours (mean ~7 hours) in healthy subjects; in patients with rheumatoid arthritis, similar half-life supports twice-daily dosing
Protein binding	~52% bound, primarily to albumin and α1-acid glycoprotein
Volume of Distribution	Volume of distribution: 97–101 L (approx 1.2–1.5 L/kg indicating extensive extravascular distribution); suggests distribution into tissues
Bioavailability	Oral bioavailability: ~75% (with high-fat meal increases exposure by 20–25%, clinical effect minimal; take with or without food)
Onset of Action	Oral: clinical improvement observed within 1–2 weeks for rheumatoid arthritis; for ulcerative colitis, response seen as early as 2 weeks
Duration of Action	Sustained response with continued twice-daily dosing; loss of effect may occur within weeks of discontinuation; not intended for intermittent use

Classification & Brands

Dosing & administration

15 mg orally once daily, with or without food.

Dosage form	TABLET, EXTENDED RELEASE
Renal impairment	No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min). Not recommended in severe renal impairment (eGFR <30 mL/min).
Liver impairment	No dose adjustment in mild hepatic impairment (Child-Pugh A). Not recommended in moderate or severe hepatic impairment (Child-Pugh B or C).
Pediatric use	Approved for pediatric patients 12 years and older with polyarticular juvenile idiopathic arthritis or psoriatic arthritis: 15 mg orally once daily. For atopic dermatitis: pediatric patients 12-17 years, 15 mg orally once daily.
Geriatric use	No specific dose adjustment required; however, due to higher risk of infections and thrombotic events in elderly patients, use with caution. No pharmacokinetic differences observed in patients over 65 years.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for RINVOQ (RINVOQ).

Breastfeeding	No data on presence in human milk; upadacitinib is detected in rat milk. M/P ratio unknown. Breastfeeding is not recommended during therapy and for 6 days after last dose.
Teratogenic Risk	Upadacitinib is an immunomodulator; animal studies show fetal toxicity including skeletal malformations at exposures below human exposure. In humans, limited data; use is contraindicated during pregnancy. Increased risk of congenital malformations cannot be excluded, particularly in first trimester.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to upadacitinib or excipients; active serious infections, including localized infections; active TB; severe hepatic impairment (Child-Pugh C).