Sodium Phenylacetate and Sodium Benzoate
Kelas obat: Agen Antineoplastik
Panganggone Sodium Phenylacetate and Sodium Benzoate
Hiperamonemia akut
Terapi tambahan kanggo perawatan hiperamonemia akut lan encephalopathy sing gegandhengan ing pasien karo kelainan siklus urea (contone, kekurangan carbamyl phosphate synthetase [CPS], ornithine transcarbamylase [OTC], argininosuccinate synthetase [ ASS], utawa argininosuccinate lyase [ASL]); ditunjuk minangka obat yatim piatu dening FDA kanggo panggunaan iki.
Nambani episode hiperammonemia gejala akut minangka darurat sing ngancam nyawa; panggunaan cepet kabeh terapi sing dibutuhake (contone, dialisis [luwih disenengi hemodialisis], suplemen kalori, watesan protein) kanggo nyuda konsentrasi amonia penting.
Hemodialisis minangka terapi sing disenengi kanggo koma hiperammonemik neonatal akut, episode encephalopathy hiperammonemik sing moderat nganti abot, lan episode hiperamonemia sing gagal nanggapi kursus awal terapi sodium phenylacetate lan sodium benzoate. Ing pasien kasebut, administrasi natrium phenylacetate lan natrium benzoat mbantu nyegah reakumulasi amonia kanthi nambah ekskresi nitrogen sampah.
Terapi bebarengan karo IV arginin hidroklorida dibutuhake ing pasien kanthi kekurangan CPS, OTC, ASS, utawa ASL; Nanging, IV arginin hidroklorida wis contraindicated ing patients karo kurang arginase. Nunggu diagnosis spesifik, uga menehi IV arginin hidroklorida kanggo bayi hyperammonemic sing diduga kelainan siklus urea.
Yen dicurigai kelainan siklus urea adhedhasar riwayat kulawarga, dokumen hiperamonemia sadurunge menehi sodium phenylacetate lan sodium benzoate.
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Carane nggunakake Sodium Phenylacetate and Sodium Benzoate
Umum
Administrasi
IV Administrasi
Kanggo solusi lan obat informasi kompatibilitas, deleng Kompatibilitas ing Stabilitas.
Administrasi kanthi infus IV mung liwat jalur vena pusat; administrasi liwat saluran periferal bisa nyebabake kobong.
Botol mung kanggo panggunaan siji.
PengenceranKudu diencerake ing injeksi dextrose 10% sadurunge administrasi.
Tansah gunakake panyaring jarum suntik steril Millex Durapore GV 33-mm (0,22 µm) sing diwenehake dening pabrikan nalika ngencerake injeksi natrium phenylacetate lan natrium benzoat tanpa preduli manawa partikel partikel katon ing vial. Partikulat wis dilaporake nanging bisa uga ora gampang diamati nalika mriksa visual; mbusak partikel iki dening Filter iki wis dikonfirmasi. (Deleng Deteksi Materi Partikulat ing Preparasi Komersial miturut Ati-ati.)
Siapkan infus IV ing wadhah kaca utawa PVC.
Temtokake volume diluent adhedhasar bobot pasien (neonatus, bayi, lan bocah sing bobote ≤20 kg) utawa BSA (bocah sing bobote > 20 kg, remaja, lan wong diwasa). Dilute saben loading utawa pangopènan dosis konsentrasi injeksi ing ≥25 mL/kg bobot awak saka 10% injeksi dextrose.
Rate of AdministrationAdministrasi loading dose liwat 90-120 menit.
Administrasi dosis pangopènan luwih saka 24 jam.
Dosis
Kasedhiya minangka sodium phenylacetate lan sodium benzoate; dosis sing dituduhake ing syarat-syarat uyah.
Dosis dhasar ing neonates, bayi, lan bocah-bocah sing bobote ≤20 kg ing bobot awak; dosis dhasar ing pasien pediatrik sing bobote> 20 kg lan ing wong diwasa ing area permukaan awak.
Pasien Pediatrik
Hiperamonemia Akut IVPasien Pediatrik sing bobote ≤20 kg: Loading dosis 250 mg/kg sodium phenylacetate ing kombinasi tetep karo 250 mg/kg sodium benzoate infused liwat 90-120 menit. Dosis pangopènan 250 mg / kg natrium phenylacetate lan 250 mg / kg natrium benzoat sing diinfus sajrone 24 jam.
Pasien pediatrik sing bobote > 20 kg: Loading dosis 5,5 g/m2 sodium phenylacetate lan 5,5 g/m2 sodium benzoate infused liwat 90-120 menit. Dosis pangopènan 5,5 g / m2 natrium phenylacetate lan 5,5 g / m2 natrium benzoat infus sajrone 24 jam.
Terusake infus pangopènan nganti konsentrasi amonia plasma sing munggah pangkat mudhun menyang tingkat normal utawa nganti pasien bisa ngidinke nutrisi lisan lan terapi obat.
Baleni Loading Dosis IVProdusen negara ora mbaleni loading dosis; Nanging, sawetara ahli nyatakake yen dosis loading baleni sajrone 24 jam kudu dianggep mung ing neonatus kanthi kelainan abot lan / utawa sing nampa dialisis; papan loading dosis ≥6 jam saben. (Deleng Pemantauan Laboratorium lan uga deleng Repeat Loading Dosis ing Ati-ati.)
Dewasa
Hiperamonemia akut IVDosis loading: 5,5 g/m2 sodium phenylacetate lan 5,5 g/m2 sodium benzoate infused over 90-120 menit. Produsen nyatakake ora mbaleni dosis loading.
Dosis pangopènan: 5,5 g/m2 sodium phenylacetate lan 5,5 g/m2 sodium benzoate infused liwat 24 jam.
Terusake infus pangopènan nganti konsentrasi amonia plasma sing munggah pangkat mudhun menyang tingkat normal utawa nganti pasien bisa ngidinke nutrisi lisan lan terapi obat.
Populasi Khusus
Ora ana rekomendasi dosis populasi khusus ing wektu iki. (Deleng Gangguan Hepatik lan Deleng Gangguan Renal ing Ati-ati lan uga deleng Populasi Khusus ing Farmakokinetik.)
Pènget
Kontraindikasi
Pènget/PanandhapPènget
Perawatan Darurat Hiperamonemia
Risiko karusakan otak kanthi cepet utawa mati yen hiperammonemia gejala akut ora bisa dikontrol; nambani minangka darurat sing ngancam nyawa. Panggunaan cepet kabeh terapi kanggo nyuda konsentrasi amonia serum (contone, dialisis [luwih disenengi hemodialisis]) penting. (Deleng Hiperamonemia Akut ing Panggunaan.)
Atur hiperamonemia amarga kesalahan metabolis bawaan ing koordinasi karo personel medis sing kenal karo kondisi kasebut; biasane mbutuhake fasilitas kesehatan sing bisa nyedhiyakake perawatan multidisiplin (contone, hemodialisis, manajemen nutrisi, dhukungan medis).
Pemantauan LaboratoriumNgawasi kanthi rapet konsentrasi amonia plasma, status neurologis, tes laboratorium, lan respon klinis sajrone perawatan.
Monitor konsentrasi elektrolit serum; njaga ing kisaran normal.
Kehilangan kalium ing urin tambah kanthi ekskresi anion sing ora bisa diserap phenylacetylglutamine lan hippurate; kanthi ati-ati ngawasi konsentrasi kalium plasma lan menehi terapi pengganti, yen perlu.
Tindakake profil kimia getih lan evaluasi pH getih lan gas getih (contone, pCO2) kanggo mriksa keracunan kaya salisilat. (Waca Salicylate-like Toxicity ing Cautions.)
Klompok Konferensi Gangguan Siklus Urea lan sawetara ahli nyaranake ngawasi konsentrasi plasma obat-obatan pemulung amonia (contone, natrium phenylacetate lan natrium benzoat) kanggo nyegah keracunan. Timbang risiko overdosis nglawan keuntungan potensial saka mbaleni dosis loading yen ora ana fasilitas kanggo ngawasi konsentrasi obat. (Deleng Repeat Loading Dosis ing Dosis lan Administrasi lan uga deleng Repeat Loading Dosis ing Cautions.)
Kemungkinan Kesalahan ResepPara ahli nyaranake mriksa kaping pindho akurasi pesenan resep kanggo nyegah kemungkinan overdosis.
Deteksi saka Materi Partikulat ing Preparasi KomersialMateri partikel wis dideteksi ing injeksi natrium fenilasetat lan natrium benzoat. Partikulat bisa uga ora gampang diamati nalika mriksa visual. Amarga partikel kasebut bisa mengaruhi safety injeksi, gunakake panyaring jarum suntik steril Millex Durapore GV 33-mm (0,22 µm) sing diwenehake dening pabrikan nalika ngencerake injeksi (pirsani Pengenceran ing Dosis lan Administrasi). Mbusak partikel kasebut kanthi panyaring iki wis dikonfirmasi.
Lapokake masalah kualitas utawa efek sing dicurigai ala menyang pabrikan (800-900-6389) utawa program FDA MedWatch.
Kanggo informasi tambahan, deleng [Web] utawa [Web].
EkstravasasiAja menehi injeksi konsentrat undiluted; mung ngatur liwat garis tengah. Administrasi vena perifer bisa nyebabake kobong.
Extravasation menyang jaringan perivenous bisa nyebabake nekrosis kulit. Kanthi ati-ati ngawasi situs infus sajrone infus. Yen dicurigai ekstravasasi, mandhegake infus lan nerusake menyang situs liyane, yen perlu. Perawatan kanggo ekstravasasi bisa uga kalebu aspirasi sisa obat saka kateter, elevasi anggota awak, lan pendinginan intermiten kanthi bungkus kadhemen.
Isi SodiumSaben g sodium phenylacetate nyedhiyakake 6,3 mEq (145 mg) sodium, lan saben g sodium benzoate nyedhiyakake 7 mEq (160 mg) sodium; saben mL konsentrasi injeksi sing dilabeli ngemot 100 mg saben sodium phenylacetate lan sodium benzoate nyedhiyakake 1,33 mEq (30,5 mg) sodium.
Coba isi sodium lan gunakake kanthi ati-ati, yen kabeh, ing pasien CHF, gangguan ginjel abot, utawa retensi sodium kanthi edema. Yen efek saleh sing ana gandhengane karo tambah konsentrasi sodium, mandhegake obat kasebut, evaluasi kanthi cepet pasien, lan njupuk langkah-langkah sing cocog.
Toksisitas kaya salisilatSacara struktur padha karo salisilat; kamungkinan efek saleh (umpamane, hiperventilasi, asidosis metabolik) biasane ana gandhengane karo keracunan salisilat akut. (Deleng Pengawasan Laboratorium ing Cautions.)
Toksisitas Utama
NeurotoxicityEfek neurotoksik sing ala (contone, ngantuk, lemes, pusing, sirah, dysgeusia, hypoacusis, disorientasi, gangguan memori, exacerbation neuropati sing ana) sing dilapurake ing pasien kanker sing nampa fenilasetat IV. Onset akut (utamane entheng) dumadi nalika wiwitan terapi; bisa dibalèkaké nalika mandheg saka tamba.
Pancegahan Umum
Baleni Loading DosisProdusen nyatakake yen, amarga konsentrasi plasma phenylacetate saya suwe, aja mbaleni dosis loading. Nanging, sawetara ahli nyatakake yen dosis loading baleni sajrone 24 jam kudu dianggep mung ing neonatus kanthi kelainan abot lan / utawa sing nampa dialisis; dosis loading papan paling sethithik 6 jam. (Deleng Repeat Loading Dosis ing Dosis lan Administrasi lan deleng Laboratory Monitoring ing Cautions.)
HiperbilirubinemiaRisiko hiperbilirubinemia ora langsung. Gunakake kanthi ati-ati ing neonatus kanthi hiperbilirubinemia. Ing bayi sing beresiko, nyuda konsentrasi bilirubin serum menyang kisaran normal sadurunge miwiti terapi karo sodium phenylacetate lan sodium benzoate.
DialisisProdusen nyatakake obat kasebut minangka pelengkap karo dialisis (contone, hemodialisis standar, dialisis peritoneal, hemofiltrasi arteriovenous).
Populasi Spesifik
KandhutanKategori C.
LaktasiOra dingerteni manawa natrium phenylacetate utawa natrium benzoat utawa metabolit konjugasi kasebut disebarake menyang susu. Gunakake kanthi ati-ati ing wanita sing nyusoni.
Panggunaan PediatrikEfikasi ditetepake kanggo perawatan hiperamonemia ing pasien bocah umur 0-16 taun, kalebu neonatus (umur 0-30 dina) lan bayi (31 dina-2). taun).
Gunakake kanthi ati-ati ing neonatus kanthi hiperbilirubinemia. (Deleng Hiperbilirubinemia ing Cautions.)
Gangguan HepatikGunakake kanthi ati-ati ing pasien sing duwe gangguan hepatik. (Deleng Metabolisme ing Farmakokinetik.)
Gagal GinjalGunakake kanthi ati-ati lan ngawasi pasien kanthi gagal ginjal. (Deleng Eliminasi miturut Farmakokinetik.)
Efek Umum sing Sabar
Muntah, hiperglikemia, hipokalemia, kejang, gangguan mental.
Apa obatan liyane bakal mengaruhi Sodium Phenylacetate and Sodium Benzoate
Ora ana studi interaksi obat resmi nganti saiki.
Obat Spesifik
Obat
Interaksi
Agen anti-infèksi (contone, penisilin)
Sawetara agen anti-infèksi bisa saingan karo phenylacetylglutamine lan hippurate kanggo sekresi tubular ginjal sing aktif, sing mengaruhi disposisi obat
Kortikosteroid
Kortikosteroid bisa nambah konsentrasi amonia plasma. kanthi nyebabake katabolisme protein
Probenecid
Probenecid nyegah transportasi senyawa organik saka ginjel (kalebu asam aminohippuric)
Probenecid bisa mengaruhi ekskresi phenylacetylglutamine lan hippurate dening ginjel
Asam valproat
Asam valproat bisa nyebabake hiperamonemia liwat inhibisi N-asetilglutamat, faktor ko-faktor sintetase karbamil fosfat
Panganggone bebarengan bisa nyebabake gangguan siklus urea lan antagonisme amonia plasma. - ngedhunake efek saka amonia detoxicant
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