Upadacitinib

Oral
Rheumatoid arthritis

Severe (Child-Pugh class C): Contraindicated.

May be taken with or without food. Swallow whole, do not split/crush/chew.

Active TB; active serious infection, including localised infections. Severe hepatic impairment. Pregnancy and lactation. Concomitant administration with live vaccines.

Patient with risk factors for gastrointestinal perforation (e.g. history of diverticulitis, receiving NSAIDs); known malignancy; risk factors for CV disorders (e.g. hypertension, hyperlipidaemia); chronic or recurrent infection, history of serious or an opportunistic infection, exposure to TB, travel history or resided in areas of endemic TB or endemic mycoses; underlying conditions predisposing to infection; risk factors for DVT or pulmonary embolism (e.g. personal history, obesity, undergoing major surgery, prolonged immobilisation). Consider anti-TB treatment before starting upadacitinib in patients with previously untreated latent TB or those at risk of TB infection. Prior to therapy initiation, patients must receive all recommended vaccinations (including prophylactic zoster vaccine) according to current immunisation guidelines. Not recommended to be used in combination with potent immunosuppressants (e.g. azathioprine, ciclosporin), other JAK inhibitors or biologic DMARDs. Severe renal impairment.

Significant: Gastrointestinal perforation, haematologic abnormalities (e.g. lymphopenia, anaemia, neutropenia), reactivation of viral infection (e.g. herpes zoster, hepatitis B), malignancies (e.g. lymphoma, non-melanoma skin cancer), elevated hepatic transaminase (e.g. AST/ALT), increased lipid parameters (e.g. total cholesterol, LDL, HDL).
Gastrointestinal disorders: Nausea.
General disorders and administration site conditions: Pyrexia.
Infections and infestations: Upper respiratory tract infection.
Investigations: Increased blood creatine phosphokinase, increased weight.
Respiratory, thoracic and mediastinal disorders: Cough.
Potentially Fatal: Serious infections (e.g. bacterial meningitis, cryptococcosis, pneumocytosis, cellulitis, multidermatomal herpes zoster, pulmonary or extrapulmonary TB, oral/oesophageal candidiasis); thrombosis (e.g. DVT, pulmonary embolism, arterial thrombosis).

Before therapy initiation, confirm pregnancy status in women of reproductive potential. Obtain lymphocyte count, neutrophil count, CBC, and LFT at baseline and periodically thereafter. Monitor lipid profile 12 weeks after starting the treatment. Evaluate for TB or latent TB infection prior to and during therapy. Screen for viral hepatitis and check for reactivation before initiation and during treatment. Perform periodic skin exam in patients at increased risk for skin cancer. Assess for signs and symptoms of infection, TB, and thrombosis during and after therapy.

Additive immunosuppression with potent immunosuppressants (e.g. azathioprine, ciclosporin, tacrolimus), biologic DMARDs, or other JAK inhibitors. Increased exposure with strong CYP3A4 inhibitors (e.g ketoconazole, clarithromycin). Decreased exposure resulting in reduced therapeutic effect with strong CYP3A4 inducers (e.g phenytoin, rifampicin).
Potentially Fatal: May enhance the toxic effects of live vaccines.

Description:
Mechanism of Action: Upadacitinib is a selective and reversible inhibitor of Janus kinase (JAK) enzymes (preferentially JAK1 or JAK1/3), which are intracellular enzymes involved in the stimulation of haematopoiesis and immune cell function through a signalling pathway. Inhibition of JAK leads to the prevention of phosphorylation and activation of signal transducers and activators transcription (STATs) which modulate intracellular activity and gene expression.
Pharmacokinetics:
Absorption: Time to peak plasma concentration: 2-4 hours.
Distribution: Plasma protein binding: 52%.
Metabolism: Metabolised in the liver mainly by CYP3A4 isoenzyme, and to a minor extent by CYP2D6.
Excretion: Via urine (24% as unchanged drug); faeces (38% as unchanged drug). Terminal elimination half-life: 8-14 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 58557659, Upadacitinib. https://pubchem.ncbi.nlm.nih.gov/compound/Upadacitinib. Accessed July 26, 2021.

Store below 30°C. Protect from moisture.

Disease-Modifying Anti-Rheumatic Drugs (DMARDs) / Immunosuppressants

L04AF03 - upadacitinib ; Belongs to the class of Janus-associated kinase (JAK) inhibitors. Used as immunosuppressants.

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