Upadacitinib


Generic Medicine Info
Indications and Dosage
Oral
Rheumatoid arthritis
Adult: Moderate to severe active cases in patients who have an inadequate response or are intolerant to ≥1 disease-modifying antirheumatic drugs (DMARDs): As monotherapy or in combination with methotrexate: 15 mg once daily. Do not initiate therapy in patient with absolute lymphocyte count (ALC) <500 cells/mm3, absolute neutrophil count (ANC) <1,000 cells/mm3, or Hb levels <8 g/dL. Dosing interruption may be required according to individual safety and tolerability (refer to detailed product guideline).
Hepatic Impairment
Severe (Child-Pugh class C): Contraindicated.
Administration
May be taken with or without food. Swallow whole, do not split/crush/chew.
Contraindications
Active TB; active serious infection, including localised infections. Severe hepatic impairment. Pregnancy and lactation. Concomitant administration with live vaccines.
Special Precautions
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.
Adverse Reactions
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).
Monitoring Parameters
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.
Drug Interactions
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.
Action
Description: 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.
Chemical Structure

Chemical Structure Image
Upadacitinib

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.

Storage
Store below 30°C. Protect from moisture.
ATC Classification
L04AA44 - upadacitinib ; Belongs to the class of selective immunosuppressive agents. Used to induce immunosuppression.
References
AbbVie Limited. Rinvoq 15 mg Modified Release Tablets data sheet 14 January 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 09/07/2021.

Anon. Upadacitinib. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 21/07/2021.

Anon. Upadacitinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/07/2021.

Joint Formulary Committee. Upadacitinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/07/2021.

Rinvoq 15 mg Extended-Release Film-Coated Tablets (AbbVie Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 09/07/2021.

Rinvoq 15 mg Prolonged-Release Tablets (AbbVie Ltd.). MHRA. https://products.mhra.gov.uk. Accessed 06/07/2021.

Rinvoq Tablet, Extended Release (AbbVie Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/07/2021.

Disclaimer: This information is independently developed by MIMS based on Upadacitinib from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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