臨床藥師日誌

 

COVID-19 Treatment Protocol

·                     Risk stratification

Mild to Moderate (輕至中度)	Severe 重度	Critical 極重度
Asymptomatic Mild: No dyspnea or CXR infiltrate Moderate: lower respiratory disease with SpO2>-94 on Room air	SpO2<94 on Room air Respiratory distress RR>30 Lung infiltrates>50%	ICU care ARDS Sepsis/septic shock Multi-organ failure

 

·                     不建議 Lopinavir/Ritonavir; interferon; colchicine; hydroxychloroquine; ivermectin, convalescent plasma]

Antiviral: Remdesivir 需向疾管署申請

·                     Recommendation for Usage o                            Severe or Critical ·                     Dosing o                            200 mg IVF on day 1, followed by 100 mg once daily from day 2-5. o                            治療時已使用呼吸器可延長至10天. ·                     Renal/hepatic dose adjustment o                            eGFR<30 not on HD: NOT recommended unless benefit > risk o                            HD: no dose adjustment (dialysis reducing concentrations by ~50%) o                            Hepatic impairment: no adjustment recommended ·                     Administration o                            凍晶乾燥注射液調製: 加入19ml注射用水，搖30秒，靜置2-3分鐘，澄清稀釋溶液濃度為5mg/ml，再打入250ml N/S(輕輕翻轉輸注袋，使混合均勻，但不要搖)。 o                            輸注時間為30-120分鐘，若發生輸注反應則降低一半輸注速率 o                            不建議用其他溶液稀釋也不建議與其他藥物同時給藥 ·                     Warning and Precaution o                            輸注反應,  AST/ALT升高 (肝臟發炎症狀需停藥或ALT>10x ULN但無症狀), prothrombin time (PT) 延長, 心律過緩。 *Remdesivir的助溶劑Sulfobutyl ether beta-cyclodextrin (SBECD)可能會累積在腎功能較差的病人，並惡化腎功能 ·                     Monitoring   o                            eGFR,  AST/ALT , Infusion reaction ·                     Drug interaction :  hydroxychloroquine (Risk X) ·         實證:無法降低死亡率。可加速恢復與減少住院時間

 

Corticosteroid: Dexamethasone

·                     Recommendation for Usage o                            Severe or critical  o                            不建議於不需要用氧氣的病人, 無資料支持使用超過 10 天 ·                     Dosing o                            6mg daily (IV or PO) for up to 10 days or until discharge. NO TAPER. o                            對懷孕女性For pregnant women (1) 無早產風險者：prednisolone 40mg daily or hydrocortisone 80mg IV BID up to 10 days (2) 有早產風險須促進胎兒肺部成熟者：dexamethasone 6mg q12h IM x 4 doses (D1-2)、prednisolone 40mg daily或 hydrocortisone 80mg IV BID (D3 起至多至 D10)。 ·                     Monitoring parameters (臨床監控項目) o                            blood sugar, mental status, fluid status ·             實證: 唯一藥物在隨機分配試驗下證實可降低死亡率

 

Interleukin-6 antagonist tocilizumab 需填臨採單

·                     Recommendation for Usage o                            台灣疾管署:  病患住院 3 天內，且入住 ICU 24 小時內或未入住 ICU 但發炎指數上升(CRP ≥ 7.5 mg/dL) o                            避免用在在免疫顯著不全、ALT>5 x ULN、胃腸道穿孔、失控的細菌真菌或非 SARS-CoV-2 感染、ANC<500、PLT<50 ·                     Dosing o                            8 mg/kg as a single dose (maximum dose: 800 mg)聯合glucocorticoids使用   o                            勿與baricitinib合用 ·                     Administration o                            使用100ml infusion bag，輸注時間60分鐘，不用特別避光 ·             Warning and Precaution (警告與注意事項 ) o                            Neutropenia and thrombocytopenia, increase LFT ·                     Monitor (監控項目) o                            Hematological profile o                            Infusion reaction, may stop and reinitiate with slower infusion rate ·     實證 : 降低使用呼吸器的時間

 

JAK inhibitor: Baricitinib 需填臨採單

·                     Recommendation for Usage o                            台灣疾管署: 與 dexamethasone，或 dexamethasone + remdesivir 合併用於住院、需使用高流量氧氣或非侵襲性呼吸器但未插管病患； 病患住院 3 天內，且入住 ICU 24 小時內或未入住 ICU 但發炎指數上升 (CRP ≥ 7.5 mg/dL) ·                     Dosing o                            4mg QD per oral for 14 days or until discharge ·                     Renal/ Hepatic dose adjustment o                            30 ≤ eGFR < 60: 2mg QD o                            15 ≤ eGFR < 30: 1mg QD o                            eGFR < 15: not recommended o                            Severe impairment: Use is not recommended (has not been studied) ·                     Administration o                            無法吞嚥者，可以嚼碎或用約10ml水溶解後服用 o                            管灌者，可以用30水(室溫)溶解後服用 ·             Warning and Precaution o           Risk of infection, increase LFT, thrombosis, lymphopenia and anemia ·                     Monitoring parameters: o                            Hematological profile, AST/ALT ·             實證: 縮短恢復時間

 

Anticoagulation (抗凝血劑)

Thromboembolic events rate among Asian population (Japan, China)6-7 All hospitalized patients: 2.9; ICU patients: 46%  DVT prophylaxis: Recommend for all critical patients.  Recommend for severe patients with Padua Score>4. Pauda score: Prior episode of VTE [3]; Thrombophilia [3]; Decreased mobility [3]; Active malignancy [3]; Previous trauma/surgery in a month [2]; Age >70 [1]; Hear/respiratory failure [1]; Ischemic stroke or MI [1]; Acute rheumatologic disorder/acute infection [1]; Obesity [1]; Hormonal therapy [1] Contraindication: PLT<30, active or recently bleed, hematoma, HIT Dose:  Enoxaparin 40mg SC daily, 30mg if CrCl<30; heparin 5000u sc q12h if HD Discontinue upon discharge DVT treatment: Consider escalation to therapeutic dose: O2>2L, elevated CRP, ferritin, procal, D-dimer>3 Dose: Enoxaparin 1mg/kg q12h (CrC<30: 1mg/kg q24h; HD: 0.8mg/kg q24h or heparin infusion APTT goal 60) Discharge with DOAC (apixaban preferred in CKD) for at least 3 months

 

Neutralizing Antibodies: bamlanivib/etesevimab; casirivimab/imdevimabmab

(即將引進台灣)

·                     Indication: For outpatient/ED use only. Mild to moderate patient at risk of progression to severe. Or admitted to the hospital for non-COVID-19 related reasons. ·                     Risk factors: o                            BMI≥35; CKD; DM, immunosuppressive disease/treatment, ≥65 y/o; ≥55 y/o with CV disease or lung disease ·                     Dose: o                            casirivimab 600mg + imdevimab 600mg IV single dose o                            bamlanivimab 700mg +estesevimab 1400mg IV (preferred) or SC single dose ·                     Adverse reaction: infusion reaction chills fever, urticarijp4a, pruritus, flushing  ·                     Bamlanivib 700mg monotherapy is not recommended; did not show a significant ↓in viral load ·                     Evidence:  o                            Decrease viral load, decrease hospitalization/ED visits

 

Supportive care (支持照顧)

o        Oxygen therapy

o        Fluid and Nutrition

o        Antipyretic

§                                     Acetaminophen is preferred over NSAIDs

§                                     Need not to discontinue NSAIDs for chronic use

o        Anti-cough medications

o        Avoid nebulization

§                                     To prevent aerosolization of SARS-CoV-2, prefer MDI or DPI

o        Stress ulcer prophylaxis in the following patients

·                                             Mechanical ventilation > 48hr

·                                             High bleeding risk (Plt< 50,000 ; INR>1.5 or APTT>2X of Normal value)

·                                             History of GI ulceration or GI bleeding within the past year

·                                             On NSAIDs or antiplatelet agents

    May consider in patients using dexamethasone

     

n          Empiric treatment for bacterial pneumonia

    Not recommended to routinely administer empiric therapy for bacterial pneumonia.

    Data suggest low rates (4-8%) of bacterial + viral co-infection with SARS-CoV-2 

    If empiric antibiotic therapy is initiated, make a microbial diagnosis and reevaluate the need to continue antibiotic therapy daily. Discontinue if procalcitonin< 0.25 with no leukocytosis 

    Empiric regimen 

·                                             Ceftriaxone 2g IV q24h (5-7 days)+ azithromycin 500mg po daily x 3 days

·                                             Piperacillin/tazobactam indicated for recent hospitalization neutropenia or when pseudomonas coverage is desired

 

·                     Reference

1.                   Taiwan CDC新型冠狀病毒（SARS-CoV-2）感染臨床處置暫行指引第十一版

2.                   台灣重症COVID-19照顧簡要指引

3.                   NIH

4.                   IDSA Guidelines on the Treatment and Management of Patients with COVID-19

5.                   COVID-19 Real-time Learning Network 

6.                   Iba et al. International Journal of Hematology. 2021. 113: 330-336

7.                   Fujiwara. J Infect Chemother. 2021. 27: 869-875

和信醫院藥劑科林蘭熙/洪維宏藥師