Methotrexate Nono Gbesiagbe Le Vodada Me: Nusita Kwasiɖa sia Kwasiɖa ƒe Atikekui Nono Gbesiagbe Nye Atikewɔwɔ Kpata¶

Methotrexate (Trexall, Rheumatrex, Otrexup, Rasuvo, Metoject) nye atike siwo woŋlɔna wu le xexeame be woatrɔ dɔlélewo na ƒunukpeƒetetedɔ, ƒunukpeƒetetedɔ, ƒunukpeƒetetedɔ, lupus, kple Crohn ƒe dɔléle dometɔ ɖeka. To vovo na atikekui bubu ɖesiaɖe kloe si le dɔnɔ ƒe atikedzraɖoƒe la, methotrexate (7.5 mg to 25 mg, si woxɔna zi geɖe be etɔ̃ va ɖo ewo 2.5 mg yellow tablets) woŋlɔ ɖi be woano ZI KPEKPE LE KWASIÐA ME le ŋkeke ɖeka si wotia dzi. Eyata methotrexate ƒe agbɔsɔsɔ si wozãna zi ɖeka kwasiɖa sia kwasiɖa le vo me gbesiagbe - le atikewɔmɔnu ƒe dzesi si tɔtɔa ame, kɔdzi yiyi ƒe dzadzraɖo ƒe vodada, dɔnɔdzikpɔla si yɔ ŋkeke 7 ƒe atikekuiɖaka me vodadatɔe, alo susu ƒe dɔwɔwɔ ƒe ɖiɖi vie ta - nye nusi dzi Atikewɔwɔ ƒe Dɔwɔna Siwo Le Dedie ƒe Dɔwɔƒe (ISMP), Xexeame ƒe Lãmesẽ Habɔbɔ (WHO), kple... United States ƒe FDA be enye atikewo zazã ƒe vodada siwo bɔ wu eye wowua ame wu le ame tsitsiwo me be "wole ŋudzɔ vevie" la dometɔ ɖeka. Nusi to vovo na emae nye be methotrexate tab siwo wonona zi ɖeka ƒe agbɔsɔsɔ gã ɖeka mimi (abe ɖevi alo ame tsitsi si mi blaeve ene 2.5 mg atikekuiwo katã zi ɖeka) ƒã hafi wòhea aɖi sesẽ vɛ elabena amegbetɔ ƒe dɔgbo ƒe folate transporter si yɔ fũu (PCFT) ate ŋu axɔ agbɔsɔsɔ sue aɖe ko le ɣeyiɣi ɖeka me eye ayiku siwo le lãmesẽ me ɖea susɔea doa goe le gaƒoƒo ʋɛ aɖewo ko me. To vovo kura na ema la, xɔ gɔ̃ hã 5 mg to 15 mg methotrexate gbesiagbe hena ŋkeke 4 va ɖo 7+ tsiã ɖe enu léa atikewo zazã atraɖii, gaƒoƒo bliboa katã me ɖe asi le lãmenugbagbeviwo ƒe mama ƒe tsatsam ɖesiaɖe me, léa methotrexate polyglutamates ɖe lãmenugbagbeviwo me eye wòhea catastrophic bone marrow aplasia (pancytopenia kple agranulocytosis), necrotic oral and gastrointestinal ulceration vɛ (mucositis), ayiku ƒe abi kpata, aklã me aɖi, kple neutropenic septic shock si wua ame. Nusi gavloe wue nye be, Folic Acid (Vitamin B9) si woƒlena le atikedzraƒe dzro ko MATEŊU atrɔ methotrexate ƒe aɖi o elabena methotrexate xe mɔ na enzyme si hiã be wòana folic acid (dihydrofolate reductase, DHFR) nawɔ dɔ la keŋkeŋ; agbetsitsi bia be woado Folinic Acid (Leucovorin / Calcium Folinate) alo Levoleucovorin si wowɔ do ŋgɔ le kɔdzi enumake, sodium bicarbonate si wodona ɖe ʋuka me ƒe alkalinization si me wowɔa adã le, eye ne ayiku ƒe dɔmawɔmawɔ nyuie la, Glucarpidase (Voraxaze) si wogbugbɔ ƒo ƒui.

Ne wò alo wò lɔlɔ̃tɔ aɖe mieno methotrexate-tikewo kwasiɖa sia kwasiɖa le vo me ŋkeke 3 alo esi wu nenema ɖe wo nɔewo yome (alo mieno kwasiɖa sia kwasiɖa ƒe agbɔsɔsɔ evelia kaba akpa), alo ne ame aɖe si le methotrexate zãm la xɔ nu me abi si le veve sem, eƒe ŋɔti me abi, dzoxɔxɔ, abi, alo aɖuɖɔ yibɔ la, ƒo ka na wò nutoa me xexlẽdzesi kpata (911 le United States kple Canada, 112 le Europa Dukɔwo ƒe Habɔbɔ bliboa me, 999 le United Kingdom) to míaƒe xexlẽdzesi siwo wozãna kpata directory alo Poison Control enumake, eye nàto eme sepsis kple septic shock ƒe ʋuʋu, . 5-fluorouracil kple capecitabine ƒe atikewo zazã wògbɔ eme, kple aɖi si wotsɔna naa kpekpeɖeŋu gbãtɔ.

Wɔ esia fifia¶

1. DZUDZƆ Methotrexate ƒe agbɔsɔsɔ bubuwo katã zazã EYE dzudzɔ NSAID kple PPIwo katã enumake: Mègano methotrexate ƒe atikekui alo atike bubu o. Le ɣeyiɣi ma ke me la, lé atike siwo me steroid mele o siwo tsia dzodzodzoetsitsi nu (NSAIDs: ibuprofen, naproxen, meloxicam, celecoxib, aspirin), proton pump inhibitors (PPIs: omeprazole, pantoprazole), kple trimethoprim-sulfamethoxazole (Bactrim / Septra), siwo katã xea mɔ na ayikuwo enumake la ɖe asi enumake methotrexate si dona le lãme na ame eye wònaa amewuwu gagblẽna ɖe edzi kabakaba.
2. Yi Dɔwɔƒe si Kpɔa Nudzɔdzɔ Kpatawo Gbɔ alo nàƒo ka na Aɖi Dzɔdzɔmenuwo enumake ne wozã methotrexate gbesiagbe hena ŋkeke 3 alo esi wu nenema tsiã ɖe enu - NE AMEA SE LE EME BE YENYE 100% VO DODO: Mègalala gbeɖe be dzesiwo nadze o. Le methotrexate zazã gbesiagbe ŋkeke 3 va ɖo 5+ megbe la, ƒumeŋuɖui ƒe lãmenugbagbeviwo kple dɔgbo ƒe lãkusiwo le kukum le ɖoɖoezizi me xoxo, togbɔ be ŋkeke gbãtɔ ƒe ʋu ƒe xexlẽme (CBC) kple serum methotrexate ƒe agbɔsɔsɔ ate ŋu adze abe ɖe wòle sue le mɔ si blea ame nu alo "womate ŋu ade dzesii o" hã. Folinic Acid (Leucovorin) dze egɔme kaba hafi nu me abi kple neutropenia dzena xɔa ame ƒe agbe.
3. Mègatsɔ Folic Acid (Vitamin B9) si womeƒlena o ɖɔ li Folinic Acid (Leucovorin) si woŋlɔ na wò gbeɖe o: Nono atike ʋɛ aɖewo siwo wozãna ɖaa 1 mg folic acid tablets tso atikedzraƒe MAWƆ dɔ o eye MAkpɔ tawò o. Folic acid mewɔa dɔ le lãmenugbagbeviwo me o vaseɖe esime enzyme dihydrofolate reductase (DHFR) - enzyme si tututu methotrexate tu la trɔe. Dɔnɔa hiã Folinic Acid (Leucovorin / Calcium Folinate / . 5-formyltetrahydrofolate) alo Levoleucovorin, si toa DHFR enzyme si woxe mɔ na la ŋu keŋkeŋ be wòagadze DNA ƒe wɔwɔ gɔme ake.
4. Dzro nu me, nuyiwo, kple aɖuwo me kpɔ be "Herald Ulcers" (Oral Stomatitis / Mucositis) gbãtɔwo hã le eme: Elabena lãmenugbagbevi siwo le nu kple ŋɔti me la ma ŋkeke 3 va ɖo 5 ɖesiaɖe, bibibi si me vevesese le, dzobibi, kpe ɣi/ɣi, alo abi siwo me goglo o le ŋgonu, nuyi, aɖe, alo aɖuwo me lae nye #1 dɔdaƒe ƒe nuxlɔ̃amedzesi gbãtɔ be methotrexate le ƒumeŋuɖui kple dɔgbo ƒe dɔwɔwɔ gblẽm vevie (mucositis doa ŋgɔ na ƒumeŋuɖui ƒe dɔmawɔmawɔ nyuie gaƒoƒo 24 va ɖo 72).
5. Lé ŋku ɖe amea ƒe dzoxɔxɔ ŋu eye nàda asrã ɖesiaɖe (>= 38.0 C / 100.4 F) abe Neutropenic Sepsis si ate ŋu ade eƒe agbe afɔku me: Le dɔnɔ si no methotrexate gbesiagbe (alo amesi ƒe ayiku ƒe dɔwɔwɔ ɖiɖi esime wònɔ methotrexate zãm kwasiɖa sia kwasiɖa) gome la, dzoxɔxɔ, vuvɔ, ŋɔti me veve, kɔdzidɔ, alo tɔtɔ fia febrile neutropenia (zero infection-fighting neutrophil white blood cells) eye wòhiã be woawɔ dɔ kpata dɔlékuiwutike siwo ƒe dɔwɔwɔ keke ta de ʋuka me le aɖabaƒoƒo 60 me.
6. Xlɔ̃ nu atikewɔla si le xɔ si me wowɔa dɔ kpata le: Mègaɖo ŋu ɖe Serum Methotrexate ƒe agbɔsɔsɔ si le ʋu me "si bɔbɔ alo esi mesɔ o" ɖeka ko ŋu le gbesiagbe agbɔsɔsɔ si gbɔ eme si nɔa anyi didi me o: Kɔdzi ƒe nomograms for serum methotrexate levels (> 10 micromol/L at 24h) wowɔ koŋ na gaƒoƒo 24 ƒe kansadɔlékuiwo dodo ɖe lãme na ame ƒe agbɔsɔsɔ gã si wozãna le ʋuka me. Le dɔnɔ aɖe si xɔ 10 mg ne wonoe gbesiagbe hena ŋkeke 7 la, serum methotrexate ƒe agbɔsɔsɔ ate ŋu axlẽ < 0.05 micromol/L esime wowua ame lãmenugbagbeviwo me methotrexate polyglutamates (MTX-PGs) wotu ɖe ƒumeŋuɖui kple dɔgbo ƒe lãmenugbagbeviwo me si hea pancytopenia si wua ame vɛ. Ele be woatsɔ Leucovorin ada gbe sia gbe agbɔsɔsɔ si gbɔ eme si nɔa anyi didi la vevie le ŋutinya kple dɔdaƒe/dɔdaƒe ƒe nusiwo wokpɔ nu eɖanye aleke kee methotrexate ƒe agbɔsɔsɔ le ʋumenugbagbeviɣi me le sue o.

Nyametsotsoti: Triaging acute single ingestion vs. subacute gbesiagbe dosing error vs. ayiku ƒe dɔmawɔmawɔ nyuie ƒe aɖi¶

flowchart TD
    Start["Wosusu be Methotrexate (MTX) ƒe agbɔsɔsɔme si gbɔ eme, Vodada le atike ƒe agbɔsɔsɔme zazã me, alo aɖi si le eme"] --> ClassifyType{"Dɔdamɔnu Kae Dzɔ?"}

    ClassifyType -->|Pattern 1: Chronic / Subacute Daily Dosing Error (Weekly Dose Taken Daily for >= 3 Days) OR Weekly Dose + Acute Kidney Injury / Bactrim Interaction| ChronicDanger["AFƆKU GÃTƆ: Lãmenugbagbeviwo ƒe Tsitrenɔnɔ ƒe Afɔɖeɖe Atraɖii Mɔ̃a Lãmenugbagbeviwo Me Methotrexate Polyglutamates (MTX-PGs) Le Ƒumeŋuɖui & Dɔgbo ƒe Crypts Me (De dzesii: Serum MTX Level Ate Ŋu Adze Le bɔbɔe/Esɔ)"]

    ClassifyType -->|Pattern 2: Single Acute Oral Overdose in Healthy Child/Adult (e.g., Swallowed Multiple 2.5 mg Tablets All at Once)| AcuteOral["Afɔku si le aɖi si le ɖoɖo nu si mebɔ o vaseɖe esime wòsɔ gbɔ: Dɔgbo me Folate Transporter (PCFT) Saturates Over -15-20 mg; Excess Unabsorbed in Gut & Ayiku Siwo Sɔ Klɔe Kabakaba"]

    ClassifyType -->|Pattern 3: Massive IV / High-Dose Oncology Overdose OR Accidental Intrathecal (Spinal) Overdose| MassiveIV_IT["ATIKƆME ƑE ƲUƲU: - IV-Agbɔsɔsɔme Gã + Ayiku ƒe Dɔmawɔmawɔ -> Crystalline Nephropathy & Marrow Ablation - Intrathecal Overdose -> Dzɔdzɔmeŋusẽ ƒe Arachnoiditis si yia dzi kabakaba, Status Epilepticus, Coma, Ku"]

    ChronicDanger --> ImmediateWorkup["Enumake ED Dɔwɔwɔ & Afɔɖeɖe: 1. DZUDZƆ Methotrexate, NSAIDs, PPIs, & Trimethoprim 2. Ta STAT CBC kple Vovototo (ANC, Ʋumenugbagbeviɣiwo), CMP (Creatinine, AST / ALT), & Serum MTX Dzidzenu 3. Dzro Nu me ɖa be Abi (Mucositis) hã le eme & Kpɔ Temp hena Febrile Neutropenia"]

    ImmediateWorkup --> LeucovorinStart["FOLINIC ACID (LEUCOVORIN) ƑE ƉEÐE KPƆKPƆ (MÈLALA Serum MTX ƒe Agbɔsɔsɔ O; MÈGAZÃ Folic Acid GBEÐE O): - Standard Chronic Overdose: Leucovorin 15 mg va ɖo 25 mg (alo 10-15 mg/m2) IV alo PO Gaƒoƒo 6 Ðesiaɖe - Mucositis Sesẽ / Pancytopenia / Serum MTX ƒe Dzidzi: Leucovorin 100 mg/m2 (alo 100-150 mg) IV Gaƒoƒo 3 va ɖo 6 ɖesiaɖe Vaseɖe esime Ʋu Xexlẽme Haya & Mucositis Dayɔ"]

    LeucovorinStart --> RenalSupport["Ayiku Ðeɖeɖa & Ƒumeŋuɖui Xɔname Bundle: 1. Aggressive IV Hydration + Sodium Bicarbonate Infusions be woana Aɖuɖɔ pH >= 7.5 va ɖo 8.0 (Dzi MTX Solubility 10-Fold & Mɔxexe ɖe Ayiku Tubule Tsidzadza nu) 2. Filgrastim (G-CSF 5 mcg / kg/ŋkeke SC) ne Neutropenic (ANC < 1,000) + Broad-Spectrum IV Dɔlékuiwutikewo ne Dzoxɔxɔ 3. GLUCARPIDASE (VORAXAZE 50 Units/kg IV le miniti 5 me) ne Ayiku ƒe Nuveviwɔame Sesẽ + Serum MTX si sɔ gbɔ atraɖii (> 1-2 micromol/L) ."]

    AcuteOral --> AcuteOralCare["1. Activated Charcoal (1 g/kg) if < 1-2 Hours Post-Ingestion 2. IV Hydration + Check 6-hr & 24-hr Serum MTX Level, Creatinine, & CBC 3. Give Oral/IV Leucovorin (10-15 mg/m2 Q6H for 3-12 doses) if Adult Ingested > 1 mg/kg (or > 50-100 mg) alo Ðevi Si Woɖu > 0.5 mg/kg (alo > 10-20 mg) ."]

    MassiveIV_IT --> IT_Emergency["Ne Wozã Aɖuɖɔtoe (Akɔta) wògbɔ eme le vo me: AMEGBETƆWO ƑE NU KPƆKPƆ KPƆKPƆ KPƆKPƆ KPƆKPƆ Kpata -> Wɔ Akɔta ƒe Toɖeɖe Enumake CSF Tsiɖɔɖɔ + Isotonic Saline Ventriculolumbar CSF Lavage + Intrathecal Glucarpidase (2,000 Units IT) + IV Dexamethasone + Systemic Leucovorin (MÈNA Leucovorin GBEÐE O Intrathecally - Ewua ame) ."]

Dɔlélenutsiŋutete: Nusita Wonoa Nu 10 mg Gbesiagbe hena Ŋkeke 7 Wua ame Esi Wòle Mimim 70 mg Zi geɖe la, Megblẽa nu le ame ŋu zi ɖeka o¶

Nyateƒenya siwo tsi tre ɖe wo nɔewo ŋu wu le aɖiŋutinunya me le atikewɔnyawo me dometɔ ɖekae nye nusita ɖoɖowɔɖi ƒe ɣeyiɣi didi le vevie wu miligram ƒe agbɔsɔsɔme bliboa le methotrexate si woano me:

1. Dɔgbo ƒe Xɔxlɔ̃ si Te Ðe Eme ( .PCFT) kple Ayikuwo ƒe Agbɔsɔsɔme Ðeka Klɔƒe Kabakaba¶

1. Dɔgbo ƒe Ʋuʋudedi: Methotrexate si woano mekakana le dɔgboa ƒe gli me le mɔ si mewɔa naneke o nu o; ele be woatsɔ Proton-Coupled Folate Transporter (PCFT / SLC46A1). Transporter sia saturates le agbɔsɔsɔme siwo le etame 15 mg to 25 mg (-0.2 to 0.3 mg/kg).
2. Ne ɖevi si le zɔzɔm alo ame tsitsi aɖe mi blaetɔ̃ 2.5 mg kpe gbadzɛwo (75 mg total) katã le aɖabaƒoƒo ɖeka tututu me la, dɔgbo ƒe mɔzɔla la yɔ fũu: bioavailability ɖiɖina tso 70% yi anyime va ɖo < 15% to 20%, eyata atikekuiawo ƒe akpa gãtɔ toa aɖuɖɔa me maxɔmaxɔe.
3. Short Plasma Exposure vs. The S-Phase Cell Cycle: Dose ɖeka ma ƒe akpa sue ɖesiaɖe si gena ɖe ʋuka me la, 80% va ɖo 90% dona le eme matrɔmatrɔe to ayiku siwo le lãmesẽ me dzi le gaƒoƒo 12 va ɖo 24 me. Esi wònye be methotrexate nye S-phase (DNA synthesis phase)-specific antimetabolite ta la, methotrexate ƒe ƒutsotsoe kpui ɖeka si xɔa gaƒoƒo 12 la kpɔa ŋusẽ ɖe ƒumeŋuɖui kple dɔgbo me lãmenugbagbevi sue siwo dzɔ be wonɔ DNA wɔm le gaƒoƒo ʋɛ mawo me dzi ko; ne atike la nya kɔ ko la, lãmenugbagbevi siwo susɔ siwo le ɖiɖim ɖe eme la mãna le mɔ si sɔ nu eye wogadea ƒumeŋuɖui me nuveviwɔame manɔmee.

2. Nusitae Agbɔsɔsɔme Siwo Wozãna Gbesiagbe (>= 3 to 7 Days) Ehea Lãmenugbagbeviwo me Polyglutamation si Wua ame vɛ¶

Ne dɔnɔ aɖe xɔ sue aɖe 2.5 mg to 15 mg dose gaƒoƒo 24 ɖesiaɖe (alo gaƒoƒo 12 ɖesiaɖe gɔ̃ hã) hena ŋkeke 4, 5, 7, alo 14 siwo kplɔ wo nɔewo ɖo:

1. 100% Bioavailability Every Day: Elabena gbesiagbe agbɔsɔsɔme ɖesiaɖe le sue (<= 15 mg), dɔgbo me folate tsɔtsɔ yi teƒe bubu meyɔ fũ gbeɖe o - mexɔa ** .70% to 90% ƒe atikekui ɖeka ɖesiaɖe**.
2. S-Phase Execution si Yia Edzi: Methotrexate léle ɖe ʋu me gbesiagbe léa ƒumeŋuɖui ƒe lãmenugbagbevi ɖesiaɖe, nu me ƒe lãmenugbagbevi, kple dɔgbo ƒe crypt cell ne ele gegem ɖe mitosis ƒe S-afã me, si tutua lãmenugbagbeviwo ƒe ta bliboa si le mamam la ɖa.
3. Methotrexate Polyglutamate si le lãmenugbagbeviwo me (MTX-PG) Mɔ̃ɖeɖe: Le ƒumeŋuɖui, aklã, kple dɔgbo ƒe lãmenugbagbeviwo me la, enzyme folylpolyglutamate synthetase (FPGS) tsɔa kɔsɔkɔsɔ siwo me glutamate molecule 2 va ɖo 7 bubu le la blana ɖe methotrexate ŋu, eye wòtrɔnɛ wòzua Methotrexate Polyglutamates (MTX-PG2 to eme MTX-PG7).
4. To vovo na methotrexate si le ʋu me femaxee la, polyglutamates gã siawo siwo me dzoxɔxɔ gbegblẽ le MATEŊU ado le lãmenugbagbeviwo ƒe lãkusi me eye woanɔ lãmenugbagbeviwo me kwasiɖa geɖe le serum methotrexate ƒe agbɔsɔsɔ ɖiɖi va ɖo zero megbe.
5. MTX-PGs xea Dihydrofolate Reductase (DHFR), Thymidylate Synthase (TS), kple AICAR transformylase si womate ŋu atrɔ o, si naa purine (adenine/guanine) kple pyrimidine ( .thymidine) DNA ƒe wɔwɔme.

Aɖaŋudzedze ƒe tsɔtsɔ sɔ kple wo nɔewo: Folic Acid (Vitamin B9) kple Folinic Acid (Leucovorin) kple Glucarpidase (Voraxaze) .¶

Subacute / Gbesiagbe Methotrexate Overdose ƒe Dɔdaƒe ƒe Ɣeyiɣikɔntabubu (Nusi Dzɔna Gbesiagbe)¶

Esi wònye be dɔnɔ siwo noa methotrexate kwasiɖa sia kwasiɖa gbesiagbe le vo me sena le wo ɖokui me be yewole dedie keŋkeŋ le ŋkeke geɖe gbãtɔawo me ta la, dzesidede dɔdamɔnu ƒe ŋgɔyiyi le afɔɖeɖe etɔ̃ me le vevie ŋutɔ:

1. Afɔɖeɖe 1: Lãmenugbagbeviwo me Nuƒoƒoƒu ƒe Akpa si Le Ðoɖoezizi me (Ŋkeke 1 va ɖo 4 le Gbesiagbe Dozazã):
2. Dɔnɔa sea le eɖokui me be yeƒe lãme sẽ alo lãmetutudɔ, nuɖuɖumadzroame, alo ɖeɖiteameŋu koe nɔa eŋu esime MTX-PGs ƒoa ƒu ɖe lãmenugbagbevi siwo ma wo me.
3. Action: Ne wolé atike ƒe agbɔsɔsɔme ƒe vodada le afisia (>= 3 consecutive days), dze egɔme tso Leucovorin si woano alo IV ( .15 mg every 6 hours) kple tsidede ʋuka me xea mɔ na aɖi siwo katã kloe le tsia ƒe anyime.
4. Afɔɖeɖe 2: The Herald Mucosal & Hepatorenal Phase (Ŋkeke 4 vaseɖe 8):
5. Painful Oral Stomatitis / Mucositis: Erythema si le bibim, abi siwo me goglo o siwo le veve sem le nuyi ememetɔwo, buccal mucosa, aɖe, kple aɖu sesẽ, si wɔnɛ be tsi alo aɖuɖɔ mimi nyea vevesese (odynophagia).
6. Cutaneous Psoriatic Plaque Erosion: Le dɔnɔ siwo ŋu psoriasis le gome la, kasia ŋutigbalẽ ƒe kpe siwo li xoxo la zua dzobibi, fafɛ, ʋuʋudedi, eye wòɖina ("methotrexate epidermal necrosis", si srɔ̃a Stevens-Johnson Syndrome / TEN), eye zi geɖe la, keklẽŋusẽ ƒe ʋuʋudedi si ŋdɔ ʋuna kpena ɖe eŋu.
7. Gastrointestinal & Hepatic Signs: Ʋuʋudedi, ƒodo ƒe vevesese, aɖuɖɔtoe si me tsi alo ʋu le (enteritis), aklã me transaminases siwo le dzi yim (AST/ALT), kple serum creatinine si le dzidzim ɖe edzi.
8. Afɔɖeɖe 3: Ƒumeŋuɖui ƒe Afɔku & Neutropenic Sepsis (Ŋkeke 6 vaseɖe 14+):
9. Elabena ʋumenugbagbevi ɣi siwo le tsatsam (neutrophils afã ƒe agbenɔƒe 6 to 8 hours) kple platelets (7 to 10 days) megale ƒumeŋuɖui si gblẽ teƒe o, Ʋu Xexlẽme Blibo (CBC) la gblẽna le Ŋkeke 6 kple Ŋkeke 12 dome:
   • Leukopenia sesẽ & Agranulocytosis (ANC < 500/mcL, zi geɖe 0/mcL): Dɔlékuiwo kple fungiwo toa nu kple dɔgbo ƒe akpa si me abi le la me yia ʋukawo me tẽ, si hea fulminant septic shock, aklãdɔ, kple typhlitis vɛ.
   • Trombocytopenia sesẽ ( .Platelets < 20,000/mcL): Ʋu si dona le aɖuwo me le eɖokui si, epistaxis, petechiae, melena (aɖuɖɔ si me aŋɔ yibɔ le), kple ʋu si dona le tagbɔ me.
   • Ʋusɔgbɔdɔ sesẽ: Pallor, gbɔgbɔtsixetsixe, kple tachycardia.
10. (De dzesii: Ne woɖe methotrexate ɖe vovo tso agbɔsɔsɔ si gbɔ eme gbɔ gɔ̃ hã la, ate ŋu ahe acute idiosyncratic Hypersensitivity Pneumonitis vɛ le ɣeyiɣi ɖesiaɖe me le atikewɔwɔ me, si adze kple kɔdzi ƒuƒu, dzoxɔxɔ, hypoxia, kple akpa eve siwo wotsɔ anyigba wɔe ƒe lãkusi).

Afɔɖeɖe ɖesiaɖe ƒe Kɔdzidzikpɔkpɔ ƒe Ðoɖowɔɖi na Methotrexate ƒe agbɔsɔsɔ si gbɔ eme¶

1. Folinic Acid (Leucovorin) Xɔname Dosing & "Gaƒoƒo 2 ƒe Mamã Se" tso Glucarpidase gbɔ¶

1. Mèhe Leucovorin Hehe Ðe Eme Gbeɖe O: Do Intravenous Folinic Acid (Leucovorin) ƒe agbɔsɔsɔ gbãtɔ le gaƒoƒo 1 me tso esime woɖee fia (elabena dɔgbo ƒe ʋuʋu le mucositis me gblẽa nu me ƒe xɔxlɔ̃ me eye Leucovorin ŋutɔ ƒe dɔgbo ƒe xɔxlɔ̃ yɔ fũ le etame 25 to 40 mg, zã Intravenous route ɣesiaɣi hena aɖi alo agbɔsɔsɔme si sɔ gbɔ va ɖo esi nu sẽ > 25 mg):
2. Subacute Gbesiagbe Dose Vodada (Dzesi aɖeke mele eŋu o alo esi mesẽ o, Ayiku ƒe Dɔwɔwɔ si sɔ, Serum MTX si bɔbɔ): Leucovorin 15 mg to 25 mg (alo 10 to 15 mg/m2) IV (alo PO) gaƒoƒo 6 ɖesiaɖe hena ŋkeke 3 va ɖo 7+ ya teti vaseɖe esime CBC siwo kplɔ wo nɔewo ɖo ɖo kpe neutrophil kple ʋumenugbagbevi dzĩwo ƒe xexlẽme si le dzi yim/si li ke dzi gaƒoƒo 48.
3. Dzesiwo ƒe Agbɔsɔsɔme Si Wozãna Agbɔsɔsɔme Si Nɔa Ame Ŋu Atraɖii (Mucositis, Leukopenia/Thrombocytopenia, alo AKI) ALOO Serum MTX ƒe Dzidziɖedzi (> 0.1 to 1.0 micromol/L): **Leucovorin si nye ʋumenugbagbeviɣidɔ 100 mg/m2 (alo 100 mg to 150 mg). < 0.05 micromol/L).
4. Serum MTX ƒe agbɔsɔsɔ si gbɔ eme (>= 10 micromol/L le 24h alo >= 100 micromol/L): Do Leucovorin ɖe edzi va ɖo ** .1,000 mg/m2 IV gaƒoƒo 6 ɖesiaɖe** to titina fli dzi (kpɔ serum calcium, abe alesi Calcium Folinate ƒe agbɔsɔsɔ gãwo naa calcium ƒe agba gãwo; doe blewu le <= 160 mg/minute alo nàtrɔ ɖe Levoleucovorin ŋu le 50% ƒe racemic ƒe agbɔsɔsɔme).
5. Glucarpidase (Voraxaze) Gaƒoƒo 2 ƒe Mamã ƒe Se:
6. Ne dɔnɔa xɔ ayiku ƒe abi vevie / eƒe ɖeɖeɖa si tsi megbe kple plasma methotrexate si dzina ɖe edzi atraɖii (> 1 to 2 micromol/L) eye wòxɔa Glucarpidase si wodona ɖe ʋuka me (50 Units/kg IV over 5 minutes), ɖo ŋku edzi be Glucarpidase hã mãa Leucovorin me ne wole ʋuka me le ɣeyiɣi ɖeka me.
7. Se: MÈGADO Leucovorin le gaƒoƒo 2 me DO ŊGƆ na Glucarpidase dodo alo gaƒoƒo 2 LE Glucarpidase dodo vɔ megbe, emegbe nàgadze Leucovorin dodo ɖe ʋu me ƒe agbɔsɔsɔ gã gɔme gaƒoƒo 2 le Glucarpidase megbe.
8. (Laboratory Artifact Warning: Ne wona Glucarpidase vɔ la, metabolite si wotso DAMPA la wɔa cross-react kple kɔdzi immunoassay ʋudodokpɔ siwo wozãna ɖaa hena gaƒoƒo 48 va ɖo 72, si wɔnɛ be serum methotrexate ƒe agbɔsɔsɔ dzena abe ɖe wòsɔ gbɔ alakpatɔe negbe ɖe wodzidzee to HPLC / LC-MS/MS) dzi hafi.).*

2. Aggressive Support Bundle: Aɖuɖɔtoe me Alkalinization, G-CSF, kple Mucositis Beléle¶

• **Aɖuɖɔtoe me Alkalinization & Diuresis si dona geɖe **: De isotonic sodium bicarbonate (150 mEq NaHCO3 le 1 L D5W le 150 to 250 mL/hr) be woalé aɖuɖɔ ƒe dodo ɖe te > 2 mL/kg/hr kple aɖuɖɔtoe me tsinyegoe ƒe pH >= 7.5 to 8.0; lé ŋku ɖe potassium kple magnesium ŋu nyuie eye nàɖɔli wo.
• Granulocyte Colony-Stimulating Factor (G-CSF / Filgrastim): Le dɔnɔ ɖesiaɖe si methotrexate hena vɛ neutropenia (ANC < 1,000/mcL), dze filgrastim si le ŋutigbalẽ te gɔme enumake (5 mcg/kg/day) be wòana ƒumeŋuɖui me neutrophilwo nahaya kabakaba ŋkeke geɖe, si aɖe ame siwo kuna le septic shock me dzi akpɔtɔ.
• Empiric Broad-Spectrum IV Antibiotics for Febrile Neutropenia: Ne yame ƒe dzoxɔxɔ ɖo >= 38.0 C (100.4 F) alo ANC < 500/mcL, ta ʋu ƒe dekɔnu eve eye nàdze atike si tsia tre ɖe pseudomonal beta-lactam ŋu gɔme (cefepime, piperacillin-tazobactam [kpɔ nyuie ne MTX gakpɔtɔ le tsatsam], alo meropenem) kpe ɖe vancomycin (ne Grade 3-4 nu me ʋumenugbagbeviɣidɔ sesẽ alo ŋutigbalẽ ƒe gbagbã le eme) kple fungi ƒe nutsyɔtsyɔ gɔme.
• Nu me Mucositis & Cholestyramine Kpekpeɖeŋu: Na Folinic Acid (Leucovorin) nu me tsiklɔ (swish kple taɖui/mi), viscous lidocaine/diphenhydramine/antacid nu me tsiklɔ, eye nàbu nu me Cholestyramine (4 grams PO every 6 hours) alo Multi-Dose Activated Charcoal be wòabla methotrexate si le biliary enterohepatic recirculation me le dɔgboa me.

Nutome ƒe xexlẽdzesi siwo ku ɖe nudzɔdzɔ kpatawo ŋu kple dɔwɔƒea ƒe ɖoɖowo¶

Nya siwo wobiaa amewo enuenu¶

Nukatae nyemate ŋu ano Folic Acid (Vitamin B9) atikekui bubuwo ko ne meno nye kwasiɖa sia kwasiɖa ƒe Methotrexate gbesiagbe kwasiɖa ɖeka le vo me o?¶

Folic Acid (pteroylglutamic acid) si woƒlena le atikedzraƒe alo esi woŋlɔ na ame la nye vitamin si mewɔa dɔ o si doa ŋgɔ na lãmenugbagbeviwo si mete ŋu ɖea lãmenugbagbeviwo le methotrexate zazã wògbɔa eme o. Be folic acid nawɔ dɔ le wò ŋutilã me la, ele be woatsɔ atike aɖe awɔ dɔ gbã to enzyme si woyɔna be Dihydrofolate Reductase (DHFR) dzi - si nye enzyme si tututu methotrexate xe keŋkeŋ eye wòwɔ nuwɔametɔe. Be kɔdziwo naɖe ƒumeŋuɖui kple dɔgbo ƒe lãkusiwo ta la, ele be woana Folinic Acid (si woyɔna hã be Leucovorin alo Calcium Folinate), si nye folate ƒomevi aɖe si wowɔ do ŋgɔ si toa DHFR enzyme si woxe mɔ na ŋu keŋkeŋ eye wògadzea DNA ƒe wɔwɔ gɔme enumake.

Nukatae Methotrexate mg 10 nono gbesiagbe hena ŋkeke 6 (60 mg katã) wua ame zi geɖe, evɔ zi geɖe la, ɖevi si mi 2.5 mg ƒe atikekui blaeve vɔ ene zi ɖeka (60 mg katã) ƒe dzesiwo nu mesẽna o alo womedzena kura o?¶

Ne ame aɖe mi methotrexate si wonona mg 60 zi ɖeka la, folate tsɔtsɔ yi dɔgbo suea me yɔa fũ abe mg 15 va ɖo 20 ene, eyata atikekui siwo sɔ gbɔ wu la ƒe akpa gãtɔ megena ɖe ʋukawo me gbeɖe o, eye ayiku siwo le lãmesẽ me kɔa akpa si woxɔ la le gaƒoƒo 12 va ɖo 24 me. Esi wònye be ne methotrexate wua lãmenugbagbeviwo ne wole mama vevie (ewɔa DNA le S-afã me) ta la, ne wozãe gaƒoƒo 12 kpuie la, megblẽa nu le ƒumeŋuɖui ƒe lãmenugbagbevi akpa gãtɔ ŋu o. To vovo na ema la, mg 10 nono gbesiagbe hena ŋkeke 6 siwo kplɔ wo nɔewo ɖo ɖea mɔ na dɔgboa ƒe xɔxlɔ̃ 100% gbesiagbe eye wòléa atike siwo me aɖi le ƒe agbɔsɔsɔ si yia edzi le lãmenugbagbeviwo ƒe mama ƒe tsatsam ɖesiaɖe me ɖe asi kwasiɖa blibo, si léa methotrexate polyglutamates ɖe lãmenugbagbeviwo me eye wòtutua ƒumeŋuɖui kple dɔgbo ƒe akpa bliboa ɖa.

Ne kɔdzi ƒe ʋudodokpɔ ɖee fia be nye "Serum Methotrexate Level" nye zero alo womate ŋu ade dzesii le methotrexate nono gbesiagbe kwasiɖa ɖeka megbe la, ɖe ema fia be mele dediea?¶

Ao - esia nye mɔ̃ siwo me afɔku le wu le atikewɔwɔ kpata me la dometɔ ɖeka. Kɔdzi ƒe ʋudodokpɔ si wowɔna ɖaa la dzidzea methotrexate si le tsia dzi le ʋua ƒe ʋumenugbagbevi dzĩ me femaxee ko, eye nomogram cutoff xexlẽdzesi siwo wota ɖe dodokpɔxɔ ƒe nyatakakawo dzi la ku ɖe kansa dodo ɖe ʋuka me gaƒoƒo 24 ƒe agbɔsɔsɔ gã ɖeka ko ŋu. Ne ame aɖe no methotrexate si wonona gbesiagbe hena ŋkeke geɖe la, methotrexate la gena ɖe ƒumeŋuɖui kple dɔgbo me lãmenugbagbeviwo me eye glutamate ƒe asike bubuwo kpena ɖe eŋu (si wɔa methotrexate polyglutamates) siwo xea mɔ nɛ le lãmenugbagbeviwo me kwasiɖa geɖe esime ʋumenugbagbeviɣi ƒe agbɔsɔsɔ ɖiɖina wu seɖoƒe si dodokpɔxɔa dea dzesii. Ele be dɔnɔ siwo ŋu methotrexate ƒe vodada siwo nɔa anyi didi le gbesiagbe naxɔ Intravenous Leucovorin xɔname blibo si wotu ɖe woƒe agbɔsɔsɔme si wozã ƒe ŋutinya, nu me ƒe abi, kple ʋu ƒe xexlẽme dzi - ne woƒe serum methotrexate ƒe agbɔsɔsɔ xlẽ zero gɔ̃ hã.

Nukatae wobua nu me ƒe abi si le veve sem (stomatitis) be enye aflaga dzĩ kpata le amesi le Methotrexate nom me?¶

Lãmenugbagbevi siwo le ŋgonu, nuyi, aɖu, kple ŋɔti ƒe eme la ma eye woɖɔlia wo ɖokui ŋkeke 3 va ɖo 5 ɖesiaɖe - kabakaba wu lãkusi bubu ɖesiaɖe kloe le ŋutilãa me. Ne methotrexate ɖo aɖi ƒe agbɔsɔsɔ le lãmenugbagbeviwo me (eɖanye tso gbesiagbe agbɔsɔsɔme ƒe vodada, ayiku ƒe dɔwɔwɔ ƒe ɖiɖi, alo atike ƒe kadodo abe Bactrim ene gbɔ) la, nu me ƒe lãkusie nye lãkusi gbãtɔ ŋutɔ si dzudzɔa mama eye wògbãna zua abi ƒuƒu siwo le veve sem (mucositis). Nu me ƒe abi siawo nyea nuxlɔ̃ame vevi aɖe si xɔa gaƒoƒo 24 va ɖo 72 do ŋgɔ be dɔnɔa ƒe ƒumeŋuɖui me lãmenugbagbeviwo hã dzudzɔ mama eye be neutropenia (ʋumenugbagbevi ɣi zero) kple ʋumenugbagbeviɣidɔ si ate ŋu ade eƒe agbe afɔku me la le dzɔdzɔ ge.

Nukatae wode se ɖe dɔlékuiwutike si nye Trimethoprim-Sulfamethoxazole (Bactrim / Septra) nu vevie na dɔnɔ siwo le Methotrexate nom?¶

Trimethoprim-sulfamethoxazole (si woŋlɔna zi geɖe na aɖuɖɔtoe me dɔlékuiwo, aɖuɖɔtoedɔléle, kple ŋutigbalẽdɔlélewo) dzea dɔnɔ si le methotrexate zãm dzi to mɔ eve siwo wua ame dzi le ɣeyiɣi ɖeka me: gbã la, trimethoprim xea mɔ na Dihydrofolate Reductase (DHFR) folate enzyme ma ke tututu abe methotrexate ene, si wɔnɛ be wòxea mɔ na ƒumeŋuɖui ƒe DNA katã si wɔa dɔ aduadu nuwɔwɔ; evelia, akpa evea siaa xea mɔ na ayiku ƒe ʋukawo be woagaɖe methotrexate ɖe aɖuɖɔ me o eye woɖea methotrexate ɖa le ʋu me proteinwo me, si wɔnɛ be methotrexate ƒe agbɔsɔsɔ le ʋu me kple lãmenugbagbeviwo me dzina ɖe edzi va ɖoa ame ƒe agbɔsɔsɔ si wua ame ne wozãe zi ɖeka kwasiɖa sia kwasiɖa gɔ̃ hã.

Mɔfiame siwo do ƒome kplii¶

• 5-Fluorouracil (5-FU) chemotherapy cream aƒemelãwo ɖuɖu kple amegbetɔ ƒe capecitabine zazã fũu akpa
• Sepsis kple septic shock ƒe dzesidede kple nuwɔwɔ kpata
• Ayiku ƒe abixɔxɔ sesẽ, rhabdomyolysis, kple aɖuɖɔtoe ƒe vovototodedeameme viviti
• Ʋu ƒe dodo dzi ɖuɖu sesẽ kple ʋu ƒe sisi ƒe dzidziɖedzi
• Aɖi ƒe kpekpeɖeŋunana gbãtɔ kple aɖidzikpɔkpɔ ƒe vovototodedeameme

Dzɔtsoƒewo kple dziɖuɖumegãwo ƒe mɔfiame¶

• Institute for Safe Medication Practices (ISMP): Atikewo ƒe Dedienɔnɔ ƒe Mɔnu Nyui Siwo Woɖo Tae na Kɔdziwo kple Nutoa Me Atikedzraƒewo: Mɔxexe Ðe Amewuwu Nu Gbesiagbe tsɔ wu Kwasiɖa sia Kwasiɖa Methotrexate Nono ƒe Vodadawo.
• Xexeame ƒe Lãmesẽ Habɔbɔ (WHO) & Europa Atikewo Dɔwɔƒe (EMA): Atikewo ƒe Dedienɔnɔ le Nɔnɔme Siwo Me Afɔku Gã Le Me Kple PRAC ƒe Aɖaŋuɖoɖowo Be Woaxe Mɔ Ðe Methotrexate ƒe Dodokpɔ Me Vodada Sesẽwo Kple Esiwo Wòwuna Nu.
• Atikewɔwɔ le ŋutilã godo le aɖi me (EXTRIP) Dɔwɔha & Amerika Atikewɔwɔ ƒe Aɖiŋutinunya ƒe Kɔledzi (ACMT): Dɔwɔƒe ƒe Mɔfiamewo na Methotrexate Aɖi: Folinic Acid (Leucovorin), Urinary Alkalinization, Glucarpidase, kple High-Flux Hemodialysis.
• Dukɔa ƒe Aɖiwo Ŋuti Nyatakaka Dɔwɔƒe (NPIS, United Kingdom) & Atikewo Kple Lãmesẽnyawo Gbɔkpɔha ƒe Dɔwɔƒe (MHRA): TOXBASE Dɔnɔdzikpɔƒe ƒe Dɔdaƒedzikpɔkpɔ le Methotrexate ƒe agbɔsɔsɔ si gbɔ eme kple esi nɔa anyi didi kple Trimethoprim ƒe Atikewo ƒe Kadodowo Ŋu.
• United States ƒe Nuɖuɖu Kple Atike Ŋuti Dɔwɔƒe (FDA): Nyatakaka Kple Dedienɔnɔ Ŋuti Nuxlɔ̃amewo Ŋɔŋlɔ na Methotrexate, Leucovorin Calcium, kple Voraxaze (Glucarpidase).

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Mɔfiame sia nye nyatakaka nana eye mexɔ ɖe atikewɔla bibiwo ƒe numekuku, Aɖidzikpɔkpɔ ƒe aɖaŋuɖoɖo, alo kɔdzi kansa/aɖiŋutinunya ƒe beléle teƒe o. Esi wònye be gbesiagbe methotrexate ƒe agbɔsɔsɔme ƒe vodadawo kple atikewo ƒe kadodo ate ŋu ahe ƒumeŋuɖui ƒe dɔmawɔmawɔ nyuie si ate ŋu ade ame ƒe agbe afɔku me kple septic shock vɛ ta la, míele aɖaŋu ɖom vevie be nàwɔ kpekpeɖeŋunadɔ gbãtɔ kple CPR ƒe hehexɔxɔ si ŋu woda asi ɖo to Dukɔwo Dome Atitsoga Dzĩ Habɔbɔ kple Ɣleti Dzĩ Habɔbɔwo ƒe Habɔbɔ (IFRC), miaƒe dukɔa ƒe Atitsoga Dzĩ Habɔbɔ, St John Ambulance, alo nutoa me dɔwɔƒe si ŋu woɖo kpee dzi.