Olumiant ® (baricitinib) tabletter

För fullständig produktresumé för Olumiant se FASS.

Denna information är endast avsedd för sjukvårdspersonal verksam i Sverige och som svar på din fråga. Informationen nedan är på engelska

Hur ska Olumiant® (baricitinib) Användas hos Patienter med Atopisk Dermatit och Nedsatt Njurfunktion?

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

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Baricitinib Label Information Related to Renal Impairment

Renal function was found to significantly affect baricitinib exposure.1

  • The mean ratios of AUC in patients with mild and moderate renal impairment to patients with normal renal function are 1.41 (90 % CI: 1.15-1.74) and 2.22 (90 % CI: 1.81-2.73), respectively.1
  • The mean ratios of Cmax in patients with mild and moderate renal impairment to patients with normal renal function are 1.16 (90 % CI: 0.92-1.45) and 1.46 (90 % CI: 1.17-1.83), respectively.1

In rheumatoid arthritis, 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.1

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

In atopic dermatitis, baricitinib was associated with a decrease in cystatin C (also used to estimate glomerular filtration rate) of 0.1 mg/L at week 4, with no further decrease noted up to week 16.1

Renal Impairment in Atopic Dermatitis Clinical Trials

Dose Adjustments for Renal Impairment

In the AD phase 3 studies with the highest dose of 4 mg, 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
  • received BARI 1 mg if assigned to the BARI 1 mg treatment arm.2

Patients were excluded from these phase 3 studies if they had an eGFR <40 mL/min/1.73m2.2

In the AD phase 3 studies with the highest dose of 2 mg (BREEZE-AD5 and BREEZE-AD6) patients with an eGFR <60 mL/min/1.73 mwere excluded from the studies.2

Estimated GFRs were calculated from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration Creatinine 2009 equation.2,3

Treatment Interruptions Due to Renal Impairment

In the AD phase 3 clinical trials, routine laboratory monitoring of serum creatinine to calculate eGFR was collected. Clinical trial criteria regarding study treatment interruption based on decreased eGFR is provided in Clinical Trial Criteria for Temporary Interruption and Resumption of Study Treatment Based on eGFR in AD Clinical Trials.2

Clinical Trial Criteria for Temporary Interruption and Resumption of Study Treatment Based on eGFRa in AD Clinical Trials

Atopic Dermatitis Clinical Trials

Study treatment was interrupted if

Study treatment was resumed when

BREEZE- AD1, BREEZE-AD2, BREEZE-AD3, BREEZE-AD4, and BREEZE-AD7


eGFR decreased to <40 mL/min/1.73 m2 in patients with a screening eGFR ≥60 mL/min/1.73 m2

eGFR increased to ≥50 mL/min/1.73 m2

eGFR decreased to <30 mL/min/1.73 m2 in patients with a screening eGFR ≥40 to <60 mL/min/1.73 m2

eGFR increased to ≥40 mL/min/1.73 m2

BREEZE-AD5 and BREEZ-AD6

eGFR decreased to <50 mL/min/1.73 m2

eGFR increased to ≥60 mL/min/1.73 m2

Abbreviations: AD = atopic dermatitis; eGFR = estimated glomerular filtration rate.

aBased on serum creatinine.

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

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

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

3Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604-612. https://doi.org/10.7326/0003-4819-150-9-200905050-00006

Glossary

AD = atopic dermatitis

AUC = area under the concentration-time curve

BARI = baricitinib

ESRD = end-stage renal disease

eGFR = estimated glomerular filtration rate

Datum fӧr senaste ӧversyn February 11, 2020


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