23/19. Upadacitinb- (RINVOQ)- @- (Aug-2019- Anti-rheumatic drug
Drug Interaction:
DRUG INTERACTIONS
Summary
• RINVOQ should be used with caution in patients receiving chronic
treatment with strong CYP3A4 inhibitors (e.g., ketoconazole).
• Coadministration of RINVOQ with strong CYP3A4 inducers (e.g.,
rifampin) is not recommended.
Details
1. Strong CYP3A4 Inhibitors
Upadacitinib exposure is increased when co-administered with strong CYP3A4 inhibitors (such as ketoconazole)
RINVOQ should be used with caution in patients receiving chronic treatment with strong CYP3A4 inhibitors.
2 Strong CYP3A4 Inducers
Upadacitinib exposure is decreased when co-administered with strong CYP3A4 inducers (such as rifampin), which may lead to reduced therapeutic effect of RINVOQ
Coadministration of RINVOQ with strong CYP3A4 inducers is not recommended.
Indication:
BRIEF SUMMARY
UPADACITINB -(Aug 2019)
Indn- To treat adult with moderately to severely active rheumatoid arthiritis
Comp- 15mg tablets • The recommended dose of RINVOQ is 15 mg once daily
ADR- Adverse reactions (greater than or equal to 1%) are: upper respiratory tract
infections, nausea, cough, and pyrexia.
CI- • None
WARNINGS-
• Serious Infections: Avoid use in patients with active, serious infection, including localized infections.
• Malignancy: Consider the risks and benefits of treatment prior to
initiating therapy in patients with a known malignancy.
Pat Inform-
Serious Infections
Inform patients that they may be more likely to develop infections when taking RINVOQ.
Instruct patients to contact their healthcare provider immediately during treatment if they
develop any signs or symptoms of an infection
Advise patients that the risk of herpe
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U.S. FDA APPROVED DRUGS DURING 2019
Sr.No.23
Name of the Drug- RINVOQ
Active Ingredient - Upadactinib
Pharmacological Classification-
To treat adult with moderately to severely active rheumatoid arthiritis
Date of Approval - 8/16/2019
(Ref- FDA approved List 2019 )
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
RINVOQ safely and effectively. See full prescribing information for RINVOQ. RINVOQ™ (upadacitinib) extended-release tablets, for oral use
Initial U.S. Approval: 2019
WARNING: SERIOUS INFECTIONS, MALIGNANCY, AND THROMBOSIS
See full prescribing information for complete boxed warning.
• Serious infections leading to hospitalization or death, including tuberculosis and bacterial, invasive fungal, viral, and other opportunistic infections, have occurred in patients receiving RINVOQ.
• If a serious infection develops, interrupt RINVOQ until the infection is controlled.
• Prior to starting RINVOQ, perform a test for latent tuberculosis; if it is positive, start treatment for tuberculosis prior to starting RINVOQ.
• Monitor all patients for active tuberculosis during treatment, even if the initial latent tuberculosis test is negative.
• Lymphoma and other malignancies have been observed in patients treated with RINVOQ.
• Thrombosis, including deep vein thrombosis, pulmonary embolism, and arterial thrombosis, have occurred in patients treated with Janus kinase inhibitors used to treat inflammatory conditions.
INDICATIONS AND USAGE
RINVOQ is a Janus kinase (JAK) inhibitor indicated for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate.
Limitation of Use: Use of RINVOQ in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.
Adverse Reaction:
ADVERSE REACTIONS
Adverse reactions (greater than or equal to 1%) are: upper respiratory tract
infections, nausea, cough, and pyrexia.
Contra-Indications:
CONTRAINDICATIONS
• None
WARNINGS AND PRECAUTIONS
• Serious Infections: Avoid use of RINVOQ in patients with active, serious
infection, including localized infections.
• Malignancy: Consider the risks and benefits of RINVOQ 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: RINVOQ 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 RINVOQ with live vaccines.
Dosages/ Overdosage Etc:
WARNING: SERIOUS INFECTIONS, MALIGNANCY, AND THROMBOSIS
See full prescribing information for complete boxed warning.
• Serious infections leading to hospitalization or death, including tuberculosis and bacterial, invasive fungal, viral, and other opportunistic infections, have occurred in patients receiving RINVOQ.
• If a serious infection develops, interrupt RINVOQ until the infection is controlled.
• Prior to starting RINVOQ, perform a test for latent tuberculosis; if it is positive, start treatment for tuberculosis prior to starting RINVOQ.
• Monitor all patients for active tuberculosis during treatment, even if the initial latent tuberculosis test is negative.
• Lymphoma and other malignancies have been observed in patients treated with RINVOQ.
• Thrombosis, including deep vein thrombosis, pulmonary embolism, and arterial thrombosis, have occurred in patients treated with Janus kinase inhibitors used to treat inflammatory conditions.
INDICATIONS AND USAGE
RINVOQ is a Janus kinase (JAK) inhibitor indicated for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate.
Limitation of Use: Use of RINVOQ in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.
DOSAGE AND ADMINISTRATION
• The recommended dose of RINVOQ is 15 mg once daily.
• RINVOQ may be used as monotherapy or in combination with methotrexate or other nonbiologic DMARDs.
• Avoid initiation or interrupt RINVOQ if absolute lymphocyte count is less than 500 cells/mm3 , absolute neutrophil count is less than 1000 cells/mm3 , or hemoglobin level is less than 8 g/dL. ended-release tablets: 15 mg
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Serious Infections
Inform patients that they may be more likely to develop infections when taking RINVOQ.
Instruct patients to contact their healthcare provider immediately during treatment if they
develop any signs or symptoms of an infection
Advise patients that the risk of herpes zoster is increased in patients taking RINVOQ and in some cases can be serious
Malignancies
Inform patients that RINVOQ may increase their risk of certain cancers.
Instruct patients to inform their healthcare provider if they have ever had any type of cancer
Thrombosis
Advise patients that events of DVT and PE have been reported in clinical studies with RINVOQ.
Instruct patients to tell their healthcare provider if they develop any signs or symptoms of a DVT or PE
Laboratory Abnormalities
Inform patients that RINVOQ may affect certain lab tests, and that blood tests are required before and during RINVOQ treatment
Pregnancy
Advise pregnant women and females of reproductive potential that exposure to RINVOQ during pregnancy may result in fetal harm. Advise females to inform their healthcare provider of a known or suspected pregnancy
Advise females of reproductive potential that effective contraception should
be used during treatment and for 4 weeks following the final dose of upadacitinib
Lactation
Advise women not to breastfeed during treatment with RINVOQ
Administration
Advise patients not to chew, crush, or split RINVOQ tablets
Manufactured by: AbbVie Ireland NL B.V., Sligo, Ireland
Packed and Distributed by: AbbVie Inc., North Chicago, IL 60064
RINVOQ is a trademark of AbbVie Biotechnology Ltd.
©2019 AbbVie Inc.
03-B725 August 2019
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Upadacitinib is a Janus kinase (JAK) inhibitor. JAKs are intracellular enzymes which transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoiesis and immune cell function.
2. Pharmacodynamics
Inhibition of IL-6 induced STAT3 and IL-7 induced STAT5 phosphorylation
In healthy volunteers, the administration of upadacitinib (immediate release formulation)
resulted in a dose- and concentration-dependent inhibition of IL-6 (JAK1/JAK2) - induced STAT3 and IL-7 (JAK1/JAK3)-induced STAT5 phosphorylation in whole blood.
The maximal inhibition was observed 1 hour after dosing which returned to near baseline by the end of dosing interval.
3 Pharmacokinetics
Upadacitinib plasma exposures are proportional to dose over the therapeutic dose range.
Steadystate plasma concentrations are achieved within 4 days with minimal accumulation after multiple once-daily administrations.
Absorption
Following oral administration of upadacitinib extended-release formulation, upadacitinib is absorbed with a median Tmax of 2 to 4 hours.
Coadministration of upadacitinib with a high-fat/ high-calorie meal had no clinically relevant effect on upadacitinib exposures (increased AUCinf by 29% and Cmax by 39%).
Distribution
Upadacitinib is 52% bound to plasma proteins. Upadacitinib partitions similarly between plasma and blood cellular components with a blood to plasma ratio of 1.0.
Metabolism
Upadacitinib metabolism is mediated by mainly CYP3A4 with a potential minor contribution from CYP2D6. The pharmacologic activity of upadacitinib is attributed to the parent molecule.
Elimination
Following single dose administration of [14C]upadacitinib immediate-release solution,
upadacitinib was eliminated predominantly as the unchanged parent substance in urine (24%) and feces (38%).
Specific Populations
Body Weight, Gender, Race, and AgeBody weight, gender, race, ethnicity, and age did not have a clinically meaningful effect on upadacitinib exposure
Renal Impairment
Renal impairment has no clinically relevant effect on upadacitinib exposure.
Hepatic Impairment
Mild (Child-Pugh A) and moderate (Child-Pugh B) hepatic impairment has no clinically relevant effect on upadacitinib exposure.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
The limited human data on use of RINVOQ in pregnant women are not sufficient to evaluate a drug-associated risk for major birth defects or miscarriage.
The estimated background risks of major birth defects and miscarriage for the indicated
population(s) are unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth
defects and miscarriages are 2-4% and 15-20%, respectively.
2. Lactation
Risk Summary
There are no data on the presence of upadacitinib in human milk, the effects on the breastfed infant, or the effects on milk production.
When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because of the potential for serious adverse reactions in the breastfed infant, advise patients that breastfeeding is not recommended during treatment with upadacitinib, and for 6 days (approximately 10 half-lives) after the last dose.
3 Females and Males of Reproductive Potential
Pregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to starting treatment with RINVOQ.
Contraception
Females
Based on animal studies, upadacitinib may cause embryo-fetal harm when administered to pregnant women.
Advise female patients of reproductive potential to use effective contraception during treatment with RINVOQ and for 4 weeks after the final dose.
4 Pediatric Use-
The safety and efficacy of RINVOQ in children and adolescents aged 0 to 18 years have not yet been established.
5. Geriatric Use-
Of the 4381 patients treated in the five Phase 3 clinical studies, a total of 906 rheumatoid arthritis patients were 65 years of age or older, including 146 patients 75 years and older. No differences in effectiveness were observed between these patients and younger patients; however, there was a higher rate of overall adverse events in the elderly.
6. Renal Impairment
No dose adjustment is required in patients with mild, moderate or severe renal impairment. The use of RINVOQ has not been studied in subjects with end stage renal disease ..
7. Hepatic Impairment
No dose adjustment is required in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment. RINVOQ is not recommended for use in patients with severe hepatic Reference ID: 4478363 impairment (Child Pugh C.
(12.3)].
10 OVERDOSAGE-
Upadacitinib 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 upadacitinib 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.
