Coltinib 15-MG Tablet

Upadacitinib is a Janus kinase (JAK) inhibitor. JAKs are intracellular enzymes that transmit signals arising from cytokine or growth factor- receptor interactions on the cellular membrane to influence cellular processes of hematopoiesis and immune cell function. Within the signaling pathway, JAKs phosphorylate and activate signal. Transducers and Activators of Transcription(STATs) which modulate intracellular activity including gene expression. Upadacitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs.

Rheumatoid Arthritis: 15 mg once daily.

Psoriatic Arthritis:

• Adults 18 Years of Age and Older: 15 mg once daily.

Atopic Dermatitis:

• 12 kg-65 kg (Weighing at least 40 kg): Initiate with 15 mg once daily. If an adequate response is not achieved, consider increasing the dosage to 30 mg once daily. Discontinue if an adequate response is not achieved with the 30 mg dose.
• Adults 65 Years of Age and Older: 15 mg once daily.

Ulcerative Colitis (Adult Patients):

• Induction: 45 mg once daily for 8 weeks.
• Maintenance: 15 mg once daily. A dosage of 30 mg once daily may be considered for patients with refractory, severe or extensive disease. Discontinue if an adequate therapeutic response is not achieved with the 30 mg dosage.

Crohn’s Disease (Adult Patients)

• Induction: 45 mg once daily for 12 weeks.
• Maintenance: 15 mg once daily. A dosage of 30 mg once daily may be considered for patients with refractory, severe or extensive disease. Discontinue if an adequate therapeutic response is not achieved with the 30 mg dosage.

Ankylosing Spondylitis: 15 mg once daily.

Non-radiographic Axial Spondyloarthritis: 15 mg once daily.

Polyarticular Juvenile Idiopathic Arthritis: (30 kg and greater): 15 mg once daily.

Strong CYP3A4 Inhibitors: Coltinib exposure is increased when co-administered with strong CYP3A4 inhibitors (such as ketoconazole). Coltinib should be used with caution in patients receiving chronic treatment with strong CYP3A4 inhibitors.

Strong CYP3A4 Inducers: Coltinib exposure is decreased when co-administered with strong CYP3A4 inducers (such as rifampin), which may lead to reduced therapeutic effect of Coltinib. Coadministration of Coltinib with strong CYP3A4 inducers is not recommended.

Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and nonradiographic axial spondyloarthritis: Adverse reactions (≥1%) were: upper respiratory tract infections, herpes zoster, herpes simplex, bronchitis, nausea, cough, pyrexia, acne, and headache.

Atopic Dermatitis: Adverse reactions (≥1%) are: upper respiratory tract infections, acne, herpes simplex, headache, blood creatine phosphokinase increased, cough, hypersensitivity, folliculitis, nausea, abdominal pain, pyrexia, increased weight, herpes zoster, influenza, fatigue, neutropenia, myalgia, and influenza like illness.

Ulcerative Colitis: Adverse reactions (≥5%) reported during induction or maintenance are: upper respiratory tract infections, increased blood creatine phosphokinase, acne, neutropenia, elevated liver enzymes, and rash.

Crohn’s Disease: Adverse reactions (≥5%) reported during induction or maintenance are: upper respiratory tract infections, anemia, pyrexia, acne, herpes zoster, and headache.

The limited human data on the use of Upadacitinib in pregnant women are not sufficient to evaluate a drug-associated risk for major birth defects or miscarriage. Based on animal studies, upadacitinib has the potential to adversely affect a developing fetus. Advise not to breastfeed.

Serious Infections: Avoid use of Coltinib in patients with active, serious infection, including localized infections.
Malignancy: Consider the risks and benefits of Coltinib treatment prior to initiating therapy in patients with a known malignancy.
Thrombosis: Consider the risks and benefits prior to treating patients who may be at increased risk of thrombosis. Promptly evaluate patients with symptoms of thrombosis and treat appropriately.
Gastrointestinal Perforations: Use with caution in patients who may be at increased risk.
Laboratory Monitoring: Recommended due to potential changes in lymphocytes, neutrophils, hemoglobin, liver enzymes and lipids.
Embryo-Fetal Toxicity: Coltinib may cause fetal harm based on animal studies. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.
Vaccinations: Avoid use of Coltinib with live vaccines.

Pediatric Use: No data available for pediatric patients under 2 years.

Hepatic Impairment: Coltinib is not recommended in patients with severe hepatic impairment.

Renal Impairment: For Coltinib, no dosage adjustment is needed for rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, or polyarticular juvenile idiopathic arthritis patients with mild to severe renal impairment. For atopic dermatitis, the maximum dose is 15 mg once daily with severe renal impairment. For ulcerative colitis or Crohn’s disease with severe renal impairment, the recommended dose is 30 mg once daily for induction and 15 mg once daily for maintenance. Coltinib is not recommended in end-stage renal disease for atopic dermatitis, ulcerative colitis, or Crohn’s disease.

Coltinib was administered in clinical trials up to doses equivalent in daily AUC to 60 mg extended-release once daily. Adverse events were comparable to those seen at lower doses and no specific toxicities were identified. Approximately 90% of Coltinib in the systemic circulation is eliminated within 24 hours of dosing (within the range of doses evaluated in clinical studies). In case of an overdose, it is recommended that the patient be monitored for signs and symptoms of adverse reactions. Patients who develop adverse reactions should receive appropriate treatment.

Drugs used for Rheumatoid Arthritis

Do not store above 25°C. Protect from light. Keep out of reach of children.