Olumiant ® (baricitinib) tabletter

För fullständig produktresumé för Olumiant se FASS.

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Olumiant®▼ (baricitinib): Dosering hos patienter med nedsatt njurfunktion

Den rekommenderade dosen är 2 mg en gång dagligen till patienter med kreatininclearance mellan 30 och 60 ml/min. Baricitinib rekommenderas inte till patienter med kreatininclearance <30 ml/min

Information from the label

Baricitinib induced a mean increase in serum creatinine levels of 3.8 µmol/L after two weeks of treatment, as compared to placebo, which remained stable thereafter during up to 104 weeks of treatment. This may be due to inhibition of creatinine secretion by baricitinib in the renal tubules. Consequently, estimates of the glomerular filtration rate based on serum creatinine may be slightly reduced, without actual loss of renal function or the occurrence of renal adverse events.1

Renal Impairment in Rheumatoid Arthritis Clinical Trials

In phase 3 studies, patients with an eGFR ≥40 and <60 mL/min/1.73 m2

  • received BARI 2 mg once daily if assigned to either the 2 mg or 4 mg BARI treatment arms, and 

  • were analyzed in the BARI 4-mg group if randomized to the BARI 4 mg treatment arm.2

Patients were excluded from the phase 3 studies if they had an eGFR <40 mL/min/1.73m2 calculated based on the most recent available serum creatinine using the MDRD method.2

Renal Function Subgroups for Pharmacokinetic and Safety Analyses

Renal impairment subgroups were defined using the eGFR ranges from the National Kidney Foundation Clinical Practice Guidelines for Chronic Kidney Disease. Subgroups by baseline eGFR included

  • none or normal defined as eGFR ≥90 mL/min/1.73 m2

  • mild defined as eGFR ≥60 to <90 mL/min/1.73 m2

  • moderate defined as eGFR ≥30 to <60 mL/min/1.73 m2

  • severe defined as eGFR 15 to <30 mL/min/1.73 m2, and

  • ESRD defined as requiring hemodialysis.2,3

Safety in Renal Impairment

Subgroup analyses were performed in BARI-treated patients using the renal function subgroup of none (n=1552), mild (n=1446), and moderate (n=175) dysfunction. Compared to patients with no renal impairment, patients with mild or moderate renal impairment had higher numerical EAIRs of

  • TEAEs (none 49.7, mild 52.5, moderate 60.4)

  • SAEs (none 7.0, mild 9.6, moderate 18.0), and

  • TEAEs leading to permanent discontinuation (none 4.0, mild 5.2, moderate 8.8).2

Placebo-controlled analyses do not suggest any clinically meaningful differences between BARI and placebo by baseline renal function.2

Pharmacokinetics

Baricitinib Eliminated by Glomerular Filtration and Active Secretion

Renal elimination is the principle clearance mechanism for BARI through glomerular filtration and active secretion.2

In a clinical pharmacology study, approximately 75% of the administered dose was eliminated in the urine, while about 20% of the dose was eliminated in the feces. Baricitinib was excreted predominately as unchanged drug in urine (69%) and feces (15%).2

Baricitinib Exposure by Renal Function

Baricitinib exposure was evaluated in patients with mild, moderate, and severe renal impairment, including ESRD requiring hemodialysis, compared with healthy subjects with normal renal function.2

The dose-normalized geometric mean ratios of BARI exposure (AUC) relative to healthy subjects from each of the renally-impaired cohorts were

  • 1.41 for mild

  • 2.22 for moderate

  • 4.05 for severe

  • 3.18 for ESRD with hemodialysis predose, and

  • 2.41 for ESRD with hemodialysis postdose.2

The mean terminal half-life by subgroup was

  • 8.4 hours with normal renal function

  • 10 hours with mild renal impairment, and

  • 19 hours with severe renal impairment or ESRD.2

These results suggest that renal impairment significantly affects exposure to BARI, leading to increased exposure with decreasing renal function. Baricitinib does appear to be dialyzable.2

References

1. Olumiant [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

2. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

3. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2 suppl 1):S1-S266.

Glossary

AUC = area under the concentration-time curve

BARI = baricitinib

EAIR = exposure-adjusted incidence rate

ESRD = end-stage renal disease

eGFR = estimated glomerular filtration rate

MDRD = Modification of Diet in Renal Disease

SAE = serious adverse event

TEAE = treatment-emergent adverse event

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Datum fӧr senaste ӧversyn 2018 M09 26

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