Peringatan Keamanan

LD50 information for voclosporin is not readily available.

Accidental overdose with voclosporin has been reported with; symptoms of an overdose may include headache, nausea and vomiting, infections, tachycardia, urticaria, lethargy, and tremor. An increase in blood urea nitrogen, serum creatinine, and alanine aminotransferase levels is also possible. There is no known antidote to an overdose with voclosporin. If an overdose occurs, supportive and symptomatic treatment should be initiated, in addition to discontinuation of voclosporin. Assessment of blood urea nitrogen, serum creatinine, eGFR and alanine aminotransferase levels is recommended. Prescribing information suggests contacting a poison center or medical toxicologist for the management of an overdose with voclosporin.^L31218

Voclosporin

DB11693

small molecule approved investigational

Deskripsi

Lupus nephritis (LN) is a type of glomerulonephritis occurring in patients with systemic lupus erythematosus (SLE). LN is a significant cause of renal failure, morbidity, and death in patients with SLE. Within 10 years of being diagnosed with SLE, 5-20% of those suffering from LN develop end-stage kidney disease, a fatal condition. Early and accurate intervention for LN is important in improving clinical outcomes.^A227683

Voclosporin, marketed as Lupkynis, is a calcineurin-inhibitor immunosuppressant for the treatment of LN.^L31218 This cyclosporine A analog was approved by the FDA on January 22, 2021 following promising results in clinical trials. Early intervention with voclosporin coupled with a kidney response is believed to prevent irreversible damage to the kidney and lead to better long-term clinical outcomes for patients with LN.^L31208 Voclosporin has demonstrated a more stable pharmacokinetic and pharmacodynamic relationship than cyclosporine, a higher potency than cyclosporine, and an improved metabolic profile when compared to older calcineurin inhibitors.^L31253

In July 2022, the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended voclosporin be granted marketing authorization for use in combination with mycophenolate mofetil for the treatment of adult patients with active lupus nephritis.^L43080

Struktur Molekul 2D

Berat 1214.646

Wujud solid

Peta Jejaring Molekuler

Obat Target Gen Interaksi Enzim Transporter Carrier

Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

1. Pendahuluan & Konsep

Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).

2. Sumber Data (Validasi)

Data Obat: Diekstraksi dari elemen drugbank-id dan name pada skema XML DrugBank.
Target Protein: Diambil dari elemen targets/target yang memuat polipeptida sasaran.
Genetik: Disinkronisasi dari sub-elemen gene-name dan varian snp-effects.
Genetik: Jumlah titik node dibatasi pada maksimal 10 (Slice=10) interaksi untuk menghindari tumpukan data.

3. Algoritma Visualisasi

Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.

4. Legenda Visual

Obat Utama (Pusat Analisis)

Target Protein (Mekanisme)

Gen (Faktor Genetik)

Metode ini mendukung analisis Precision Medicine dan evaluasi risiko Drug-Drug Interaction (DDI).

Profil Farmakokinetik

Waktu Paruh (Half-Life) The average terminal half-life of voclosporin is about 30 hours (24.9 to 36.5 hours).[L31218]

Volume Distribusi The apparent volume of distribution of voclosporin is 2,154 L. Voclosporin distributes extensively into red blood cells; distribution between whole blood and plasma is dependent on concentration and temperature.[L31218]

Klirens (Clearance) The mean apparent steady-state clearance of voclosporin is 63.6 L/h.[L31218] Hepatic and renal impairment significantly reduce the clearance of voclosporin.[A227708]

Absorpsi

When administered on an empty stomach, the median Tmax of voclosporin is 1.5 hours, but can range from 1-4 hours.^L31218 The AUC is estimated at 7693.6 ng/mL*h and the Cmax is estimated at 955.5 ng/mL.^A227678

Metabolisme

Voclosporin is mainly metabolized by the CYP3A4 hepatic cytochrome enzyme. Pharmacologic activity is mainly attributed to the parent molecule. A major metabolite has been detected in human whole blood, representing 16.7% of total exposure; this metabolite is about 8-fold less potent than the parent drug, voclosporin.L31218,L31228

Rute Eliminasi

Voclosporin is eliminated in the urine and feces, with about 88% detected in the feces and about 2% detected in the urine.^L31228

Interaksi Makanan

2 Data

1. Avoid grapefruit products. Avoid food or drink containing grapefruit when taking voclosporin, as it may decrease metabolism and increase exposure to this drug.
2. Take on an empty stomach. Take on an empty stomach, either 1 hour before or 2 hours after a meal and as close to 12 hours between doses as possible.

Interaksi Obat

636 Data

Denosumab	The risk or severity of adverse effects can be increased when Denosumab is combined with Voclosporin.
Etanercept	The risk or severity of adverse effects can be increased when Etanercept is combined with Voclosporin.
Peginterferon alfa-2a	The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Voclosporin.
Interferon alfa-n1	The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Voclosporin.
Interferon alfa-n3	The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Voclosporin.
Peginterferon alfa-2b	The risk or severity of adverse effects can be increased when Peginterferon alfa-2b is combined with Voclosporin.
Anakinra	The risk or severity of adverse effects can be increased when Anakinra is combined with Voclosporin.
Interferon gamma-1b	The risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Voclosporin.
Interferon alfa-2a	The risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Voclosporin.
Aldesleukin	The risk or severity of adverse effects can be increased when Aldesleukin is combined with Voclosporin.
Adalimumab	The risk or severity of adverse effects can be increased when Adalimumab is combined with Voclosporin.
Gemtuzumab ozogamicin	The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Voclosporin.
Pegaspargase	The risk or severity of adverse effects can be increased when Pegaspargase is combined with Voclosporin.
Infliximab	The risk or severity of adverse effects can be increased when Infliximab is combined with Voclosporin.
Interferon beta-1b	The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Voclosporin.
Interferon alfacon-1	The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Voclosporin.
Rituximab	The risk or severity of adverse effects can be increased when Rituximab is combined with Voclosporin.
Basiliximab	The risk or severity of adverse effects can be increased when Basiliximab is combined with Voclosporin.
Muromonab	The risk or severity of adverse effects can be increased when Muromonab is combined with Voclosporin.
Ibritumomab tiuxetan	The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Voclosporin.
Tositumomab	The risk or severity of adverse effects can be increased when Tositumomab is combined with Voclosporin.
Alemtuzumab	The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Voclosporin.
Alefacept	The risk or severity of adverse effects can be increased when Alefacept is combined with Voclosporin.
Efalizumab	The risk or severity of adverse effects can be increased when Efalizumab is combined with Voclosporin.
Antithymocyte immunoglobulin (rabbit)	The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Voclosporin.
Interferon alfa-2b	The risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Voclosporin.
Daclizumab	The risk or severity of adverse effects can be increased when Daclizumab is combined with Voclosporin.
Phenylalanine	The risk or severity of adverse effects can be increased when Phenylalanine is combined with Voclosporin.
Flunisolide	The risk or severity of adverse effects can be increased when Flunisolide is combined with Voclosporin.
Cladribine	Voclosporin may increase the immunosuppressive activities of Cladribine.
Carmustine	The risk or severity of adverse effects can be increased when Carmustine is combined with Voclosporin.
Amsacrine	The risk or severity of adverse effects can be increased when Amsacrine is combined with Voclosporin.
Bleomycin	The risk or severity of adverse effects can be increased when Bleomycin is combined with Voclosporin.
Chlorambucil	The risk or severity of adverse effects can be increased when Chlorambucil is combined with Voclosporin.
Raltitrexed	The risk or severity of adverse effects can be increased when Raltitrexed is combined with Voclosporin.
Mitomycin	The risk or severity of adverse effects can be increased when Mitomycin is combined with Voclosporin.
Vindesine	The risk or severity of adverse effects can be increased when Vindesine is combined with Voclosporin.
Floxuridine	The risk or severity of adverse effects can be increased when Floxuridine is combined with Voclosporin.
Indomethacin	The risk or severity of adverse effects can be increased when Indomethacin is combined with Voclosporin.
Tioguanine	The risk or severity of adverse effects can be increased when Tioguanine is combined with Voclosporin.
Vinorelbine	The risk or severity of adverse effects can be increased when Vinorelbine is combined with Voclosporin.
Dexrazoxane	The risk or severity of adverse effects can be increased when Dexrazoxane is combined with Voclosporin.
Beclomethasone dipropionate	The risk or severity of adverse effects can be increased when Beclomethasone dipropionate is combined with Voclosporin.
Sorafenib	The risk or severity of adverse effects can be increased when Sorafenib is combined with Voclosporin.
Streptozocin	The risk or severity of adverse effects can be increased when Streptozocin is combined with Voclosporin.
Trifluridine	The risk or severity of adverse effects can be increased when Trifluridine is combined with Voclosporin.
Betamethasone	The risk or severity of adverse effects can be increased when Betamethasone is combined with Voclosporin.
Teniposide	The risk or severity of adverse effects can be increased when Teniposide is combined with Voclosporin.
Epirubicin	The risk or severity of adverse effects can be increased when Epirubicin is combined with Voclosporin.
Chloramphenicol	The risk or severity of adverse effects can be increased when Chloramphenicol is combined with Voclosporin.
Lenalidomide	The risk or severity of adverse effects can be increased when Lenalidomide is combined with Voclosporin.
Altretamine	The risk or severity of adverse effects can be increased when Altretamine is combined with Voclosporin.
Zidovudine	The risk or severity of adverse effects can be increased when Zidovudine is combined with Voclosporin.
Cisplatin	The risk or severity of adverse effects can be increased when Cisplatin is combined with Voclosporin.
Oxaliplatin	The risk or severity of adverse effects can be increased when Oxaliplatin is combined with Voclosporin.
Cyclophosphamide	The risk or severity of adverse effects can be increased when Cyclophosphamide is combined with Voclosporin.
Fluorouracil	The risk or severity of adverse effects can be increased when Fluorouracil is combined with Voclosporin.
Propylthiouracil	The risk or severity of adverse effects can be increased when Propylthiouracil is combined with Voclosporin.
Pentostatin	The risk or severity of adverse effects can be increased when Pentostatin is combined with Voclosporin.
Methotrexate	The risk or severity of adverse effects can be increased when Methotrexate is combined with Voclosporin.
Fluticasone propionate	The risk or severity of adverse effects can be increased when Fluticasone propionate is combined with Voclosporin.
Fluocinolone acetonide	The risk or severity of adverse effects can be increased when Fluocinolone acetonide is combined with Voclosporin.
Linezolid	The risk or severity of adverse effects can be increased when Linezolid is combined with Voclosporin.
Imatinib	The risk or severity of adverse effects can be increased when Imatinib is combined with Voclosporin.
Triamcinolone	The risk or severity of adverse effects can be increased when Triamcinolone is combined with Voclosporin.
Clofarabine	The risk or severity of adverse effects can be increased when Clofarabine is combined with Voclosporin.
Prednisone	The risk or severity of adverse effects can be increased when Prednisone is combined with Voclosporin.
Pemetrexed	The risk or severity of adverse effects can be increased when Pemetrexed is combined with Voclosporin.
Fludrocortisone	The risk or severity of adverse effects can be increased when Fludrocortisone is combined with Voclosporin.
Mycophenolate mofetil	The risk or severity of adverse effects can be increased when Mycophenolate mofetil is combined with Voclosporin.
Daunorubicin	The risk or severity of adverse effects can be increased when Daunorubicin is combined with Voclosporin.
Irinotecan	The risk or severity of adverse effects can be increased when Irinotecan is combined with Voclosporin.
Sulfasalazine	The risk or severity of adverse effects can be increased when Sulfasalazine is combined with Voclosporin.
Dacarbazine	The risk or severity of adverse effects can be increased when Dacarbazine is combined with Voclosporin.
Temozolomide	The risk or severity of adverse effects can be increased when Temozolomide is combined with Voclosporin.
Penicillamine	The risk or severity of adverse effects can be increased when Penicillamine is combined with Voclosporin.
Prednisolone	The risk or severity of adverse effects can be increased when Prednisolone is combined with Voclosporin.
Mechlorethamine	The risk or severity of adverse effects can be increased when Mechlorethamine is combined with Voclosporin.
Azacitidine	The risk or severity of adverse effects can be increased when Azacitidine is combined with Voclosporin.
Carboplatin	The risk or severity of adverse effects can be increased when Carboplatin is combined with Voclosporin.
Methylprednisolone	The risk or severity of adverse effects can be increased when Methylprednisolone is combined with Voclosporin.
Cytarabine	The risk or severity of adverse effects can be increased when Cytarabine is combined with Voclosporin.
Azathioprine	The risk or severity of adverse effects can be increased when Azathioprine is combined with Voclosporin.
Hydroxyurea	The risk or severity of adverse effects can be increased when Hydroxyurea is combined with Voclosporin.
Busulfan	The risk or severity of adverse effects can be increased when Busulfan is combined with Voclosporin.
Mycophenolic acid	The risk or severity of adverse effects can be increased when Mycophenolic acid is combined with Voclosporin.
Mercaptopurine	The risk or severity of adverse effects can be increased when Mercaptopurine is combined with Voclosporin.
Thalidomide	The risk or severity of adverse effects can be increased when Thalidomide is combined with Voclosporin.
Melphalan	The risk or severity of adverse effects can be increased when Melphalan is combined with Voclosporin.
Fludarabine	The risk or severity of adverse effects can be increased when Fludarabine is combined with Voclosporin.
Flucytosine	The risk or severity of adverse effects can be increased when Flucytosine is combined with Voclosporin.
Capecitabine	The risk or severity of adverse effects can be increased when Capecitabine is combined with Voclosporin.
Trilostane	The risk or severity of adverse effects can be increased when Trilostane is combined with Voclosporin.
Procarbazine	The risk or severity of adverse effects can be increased when Procarbazine is combined with Voclosporin.
Arsenic trioxide	The risk or severity of adverse effects can be increased when Arsenic trioxide is combined with Voclosporin.
Idarubicin	The risk or severity of adverse effects can be increased when Idarubicin is combined with Voclosporin.
Ifosfamide	The risk or severity of adverse effects can be increased when Ifosfamide is combined with Voclosporin.
Estramustine	The risk or severity of adverse effects can be increased when Estramustine is combined with Voclosporin.
Mitoxantrone	The risk or severity of adverse effects can be increased when Mitoxantrone is combined with Voclosporin.
Lomustine	The risk or severity of adverse effects can be increased when Lomustine is combined with Voclosporin.

Target Protein

Guided entry of tail-anchored proteins factor CAMLG CAMLG

Protein phosphatase 3 catalytic subunit alpha PPP3CA

Calcineurin subunit B type 1 PPP3R1

Calcineurin subunit B type 2 PPP3R2

Referensi & Sumber

Artikel (PubMed)

PMID: 32669879
Li Y, Palmisano M, Sun D, Zhou S: Pharmacokinetic Disposition Difference Between Cyclosporine and Voclosporin Drives Their Distinct Efficacy and Safety Profiles in Clinical Studies. Clin Pharmacol. 2020 Jul 1;12:83-96. doi: 10.2147/CPAA.S255789. eCollection 2020.
PMID: 31974366
Anders HJ, Saxena R, Zhao MH, Parodis I, Salmon JE, Mohan C: Lupus nephritis. Nat Rev Dis Primers. 2020 Jan 23;6(1):7. doi: 10.1038/s41572-019-0141-9.
PMID: 23700374
Schultz C: Voclosporin as a treatment for noninfectious uveitis. Ophthalmol Eye Dis. 2013 May 5;5:5-10. doi: 10.4137/OED.S7995. Print 2013.
PMID: 23996158
Ling SY, Huizinga RB, Mayo PR, Freitag DG, Aspeslet LJ, Foster RT: Pharmacokinetics of voclosporin in renal impairment and hepatic impairment. J Clin Pharmacol. 2013 Dec;53(12):1303-12. doi: 10.1002/jcph.166. Epub 2013 Oct 8.

Link

Contoh Produk & Brand

Produk: 3 • International brands: 1

Produk

Lupkynis

Capsule • 7.9 mg/1 • Oral • US • Approved
Lupkynis

Capsule • 7.9 mg • Oral • EU • Approved
Lupkynis

Capsule • 7.9 mg • Oral • EU • Approved

International Brands

Lupkynis — Aurinia Pharmaceuticals Inc.

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.