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BCG vaccination may slow spread of COVID-19

Countries that had compulsory bacillus Calmette-Guérin (BCG) vaccination at least until 2000 appear to have built up a degree of “herd immunity” against COVID-19, a new study suggests.

BCG vaccination is usually given at birth or during childhood to protect against tuberculosis (TB). But there is also evidence that it protects against other respiratory infections and lung cancer. In addition, it is an effective treatment for some forms of bladder cancer.

A study in 2018 found that the vaccine appeared to “reprogram” immune cells to produce more of a particular immune signalling molecule. This, in turn, boosted immunity against viral infection. The studies found that having mandatory BCG vaccination significantly “flattened the curve” of the initial spread of COVID-19 throughout the populations studied.

Source: Medscape

Dexamethasone

Rx Prescription Required

Classes: Corticosteroids, Anti-Inflammatory Agents

Uses: Anti-Inflammatory, Allergic Conditions, Multiple Sclerosis (AE), Cerebral Edema, Shock, Multiple Myeloma, Meningitis, Dexamethasone Suppression Test, Multiple Myeloma, Spinal Cord Compression

Administration: Oral, IV, IM

Dosages ›
Interactions ›
Adverse Effects ›
Warnings ›
Safety Advice ›
Pharmacology ›

Aardex 4mg Injection

Manufacturer: Regain Laboratories

Salt Composition: Dexamethasone (4mg)

Price: Rs 8.5 (2ml in 1 vial)

Adexa 4mg Injection

Manufacturer: Alice Healthcare Pvt Ltd

Salt Composition: Dexamethasone (4mg)

Price: Rs 10.5 (2ml in 1 vial)

Alpa Dex 4mg Injection

Manufacturer: Alpa Laboratories Ltd

Salt Composition: Dexamethasone (4mg)

Price: Rs 45 (30ml in 1 vial)

Auradex 8mg Tablet

Manufacturer: Aureate Healthcare Pvt Ltd

Salt Composition: Dexamethasone (8mg) tablet

Price: Rs 60 (10 tablets in 1 strip) ₹6.0/Tablet

Biodexone 4mg Injection

Manufacturer: Zydus Cadila

Salt Composition: Dexamethasone (4mg)

Price: Rs 6.74 (2ml in 1 vial)

Biodexone 8mg Tablet

Manufacturer: Zydus Cadila

Salt Composition: Dexamethasone (8mg) tablet

Price: Rs 72 (10 tablets in 1 strip) ₹7.2/Tablet

Cortina 4mg Injection

Manufacturer: Hamax Pharmaceuticals

Salt Composition: Dexamethasone (4mg)

Price: Rs 9.42 (2ml in 1 vial)

Decdak St 0.5mg Tablet

Manufacturer: Wockhardt Ltd

Salt Composition: Dexamethasone (0.5mg) tablet

Price: Rs 2 (10 tablets in 1 strip)

Decdan 0.5mg Tablet

Manufacturer: Wockhardt Ltd

Salt Composition: Dexamethasone (0.5mg) tablet

Price: Rs 2 (10 tablets in 1 strip)

Decicort 0.5mg Tablet

Manufacturer: Galpha Laboratories Ltd

Salt Composition: Dexamethasone (0.5mg) tablet

Price: Rs 3.5 (10 tablets in 1 strip) ₹0.35/Tablet

Demisone Tablet

Manufacturer: Cadila Pharmaceuticals Ltd

Salt Composition: Dexamethasone (0.5mg) tablet

Price: Rs 2.13 (10 tablets in 1 strip) ₹0.21/Tablet

Dexaford 0.5mg Tablet

Manufacturer: Roussel Laboratories Pvt Ltd

Salt Composition: Dexamethasone (0.5mg) tablet

Price: Rs 2.2 (10 tablets in 1 strip) ₹0.22/Tablet

Dexagee 0.5mg Tablet

Manufacturer: Zydus Cadila

Salt Composition: Dexamethasone (0.5mg) tablet

Price: Rs 12.5 (100 tablets in 1 bottle) ₹0.13/Tablet

Dexahim 0.5mg Tablet

Manufacturer: Himanshu Pharmaceuticals Pvt Ltd

Salt Composition: Dexamethasone (0.5mg) tablet

Price: Rs 2 (10 tablets in 1 strip) ₹0.2/Tablet

Dexamaxx 0.5mg Tablet

Manufacturer: Maxx Farmacia (India)

Salt Composition: Dexamethasone (0.5mg) tablet

Price: Rs 26 (100 tablets in 1 bottle) ₹0.26/Tablet

Dexalide 0.5mg Tablet

Manufacturer: Allied Chemicals & Pharmaceuticals Pvt Ltd

Salt Composition: Dexamethasone (0.5mg) tablet

Price: Rs 1.94 (10 tablets in 1 strip) ₹0.19/Tablet

Dexasone 0.5mg Tablet

Manufacturer: Cadila Pharmaceuticals Ltd

Salt Composition: Dexamethasone (0.5mg) tablet

Price: Rs 1.97 (10 tablets in 1 strip) ₹0.19/Tablet

Dexona Injection

Manufacturer: Zydus Cadila

Salt Composition: Dexamethasone (4mg) Injection

Price: Rs 10.21 (2ml in 1 ampoule)

Dexona Tablet

Manufacturer: Zydus Cadila

Salt Composition: Dexamethasone (0.5mg) tablet

Price: Rs 6.38 (30 tablets in 1 strip) ₹0.21/Tablet

D Sone Tablet

Manufacturer: Akme Biotec

Salt Composition: Dexamethasone (0.5mg) tablet

Price: Rs 6.5 (20 tablets in 1 strip) ₹0.33/Tablet

Eurodex 0.5mg Tablet

Manufacturer: Euro Biogenics

Salt Composition: Dexamethasone (0.5mg) tablet

Price: Rs 1.8 (10 tablets in 1 strip) ₹0.18/Tablet

Lupidexa 0.5mg Tablet

Manufacturer: Lupin Ltd

Salt Composition: Dexamethasone (0.5mg) tablet

Price: Rs 2.15 (10 tablets in 1 strip) ₹0.21/Tablet

Wymesone 0.5mg Tablet

Manufacturer: Pfizer Ltd

Salt Composition: Dexamethasone (0.5mg) tablet

Price: Rs 2.18 (10 tablets in 1 strip) ₹0.21/Tablet

Dosages

Dosage Forms & Strengths

  • Tablet: 0.5mg, 0.75mg, 1mg, 1.5mg, 2mg, 4mg, 6mg, 20mg
  • Injectable suspension: 4mg/mL, 10mg/mL 
  • Oral solution: 0.5mg/5mL (generic)
  • Oral concentrate: 1mg/1mL (Dexamethasone Intensol)

Inflammation

  • 0.75-9 mg/day IV/IM/PO divided q6-12hr
  • Intra-articular, intralesional, or soft tissue: 0.2-6 mg/day

Multiple Sclerosis (Acute Exacerbation)

  • 30 mg/day PO for 1 week; follow by 4-12 mg/day for 1 mo

Cerebral Edema

  • 10 mg IV, then 4 mg IM q6hr until clinical improvement is observed; may be reduced after 2-4 days and gradually discontinued over 5-7 days

Shock

  • 1-6 mg/kg IV once or 40 mg IV q2-6hr PRN
  • Alternative: 20 mg IV, then 3 mg/kg/day by continuous IV infusion
  • High-dose treatment not to be continued beyond 48-72 hours

Allergic Conditions

  • Day 1: 4-8 mg IM
  • Days 2-3: 3 mg/day PO divided q12hr
  • Day 4: 1.5 mg/day PO divided q12hr
  • Days 5-6: 0.75 mg/day PO in a single daily dose
  • Day 7: No treatment

Dexamethasone Suppression Test

Low-dose test

  • Screening for Cushing syndrome
  • Overnight test: 1 mg PO between 11:00 PM and midnight; cortisol level tested between 8:00 and 9:00 AM on the following morning
  • Standard 2-day test: 0.5 mg PO q6hr (9:00 AM, 3:00 PM, 9:00 PM, 3:00 AM) for 2 days; cortisol level tested 6 hours after final dose (9:00 AM)

High-dose test

  • Confirmed Cushing syndrome in which further workup is needed to identify whether hormone excess is the result of Cushing syndrome or other causes
  • Standard 2-day test: After determination of baseline serum cortisol or 24-hr urinary free cortisol, 2 mg PO q6hr for 2 days; urine for free cortisol is collected during the test, and serum cortisol is checked 6 hours after the final dose
  • Overnight test: After determination of baseline serum cortisol, 8 mg (typically) PO between 11:00 PM and midnight; cortisol level tested between 8:00 and 9:00 AM on the following morning
  • IV test: After determination of baseline serum cortisol, 1 mg/hr by continuous IV infusion for 5-7 hours

Multiple Myeloma

  • Indicated in combination with other antimyeloma products for multiple myeloma (MM).
  • 20 or 40 mg PO qDay on specific days as per specific treatment regimen

Chemotherapy-Induced Nausea & Vomiting (Off-label)

  • 8-12 mg PO/IV alone or in combination with other antiemetics before chemotherapy, then 8 mg PO/IV q24hr for 1-3 days after chemotherapy (days 2-4)

Altitude Sickness (Off-label)

Prophylaxis

  • 2 mg PO q6hr or 4 mg PO q12hr beginning on the day of ascent; may be discontinued after 2- to 3-day stay at same elevation or initiation of descent

Treatment

  • Acute mountain sickness (AMS): 4 mg PO/IV/IM q6hr
  • High-altitude cerebral edema (HACE): 8 mg once followed by 4 mg PO/IV/IM q6hr until symptoms resolve

Spinal Cord Compression (Off-label)

  • 10-100 mg IV, then 4-24 mg IV q6hr during radiation therapy, then tapered

Dosage Forms & Strengths

  • Tablet: 0.5mg, 0.75mg, 1mg, 1.5mg, 2mg, 4mg, 6mg, 20mg
  • Injectable suspension: 4mg/mL, 10mg/mL 
  • Oral solution: 0.5mg/5mL (generic)
  • Oral concentrate: 1mg/1mL (Dexamethasone Intensol)

Airway Edema

  • 0.5-2 mg/kg/day PO/IV/IM divided q6hr, starting 24 hours before extubation and continued for 4-6 doses afterward  

Croup

  • 0.6 mg/kg PO/IV/IM once; not to exceed 16 mg  

Inflammation

  • 0.08-0.3 mg/kg/day IV/PO/IM divided q6hr or q12hr  

Meningitis

  • >6 weeks: 0.6 mg/kg/day IV divided q6hr for first 2-4 days of antibiotic therapy, starting 10-20 minutes before or simultaneously with the first antibiotic dose

Cerebral Edema associated with Brain Tumor

  • 1-2 mg/kg IV/IM once; maintenance: 1-1.5 mg/kg/day IV/IM divided q4-6hr; not to exceed 16 mg/day  

Spinal Cord Compression

  • 2 mg/kg/day IV divided q6hr  

Adrenal Cortical Hyperfunction Test

  • After determination of baseline cortisol level, 1 mg PO at bedtime
  • Plasma cortisol level then determined at 8:00 AM on the following morning; level will be decreased in normal individuals but at a baseline level in Cushing syndrome

Respiratory Distress Syndrome in Premature Infants (Off-label)

  • Prophylaxis: 4 mg IM q8hr administered to mother for 2 days before delivery

Interactions

Contraindicated

  • apixaban
  • artemether/lumefantrine
  • cariprazine
  • cobimetinib
  • dienogest/estradiol valerate
  • elbasvir/grazoprevir
  • elvitegravir/cobicistat/emtricitabine/tenofovir DF
  • lumacaftor/ivacaftor
  • lumefantrine
  • lurasidone
  • mifepristone
  • naloxegol
  • ombitasvir/paritaprevir/ritonavir & dasabuvir
  • panobinostat
  • praziquantel
  • regorafenib
  • rilpivirine
  • roflumilast
  • vandetanib

Serious

  • abemaciclib
  • acalabrutinib
  • adenovirus types 4 and 7 live, oral
  • aldesleukin
  • anthrax vaccine
  • apalutamide
  • apremilast
  • axicabtagene ciloleucel
  • axitinib
  • BCG vaccine live
  • bedaquiline
  • bosutinib
  • brigatinib
  • cabozantinib
  • carbamazepine
  • ceritinib
  • chloramphenicol
  • cimetidine
  • clarithromycin
  • cobicistat
  • copanlisib
  • dabrafenib
  • dihydroergotamine
  • dihydroergotamine intranasal
  • diphtheria & tetanus toxoids/ acellular pertussis vaccine
  • diphtheria & tetanus toxoids/acellular pertussis/poliovirus, inactivated vaccine
  • dronedarone
  • eliglustat
  • elvitegravir
  • erdafitinib
  • ergotamine
  • erythromycin base
  • erythromycin ethylsuccinate
  • erythromycin lactobionate
  • erythromycin stearate
  • ethinylestradiol
  • everolimus
  • hepatitis A vaccine inactivated
  • hepatitis a/b vaccine
  • hepatitis a/typhoid vaccine
  • hepatitis b vaccine
  • human papillomavirus vaccine, nonavalent
  • human papillomavirus vaccine, quadrivalent
  • ibrutinib
  • idelalisib
  • influenza virus vaccine quadrivalent
  • influenza virus vaccine quadrivalent, intranasal
  • influenza virus vaccine trivalent
  • influenza virus vaccine trivalent, adjuvanted
  • ivabradine
  • ivacaftor
  • ivosidenib
  • ixazomib
  • Japanese encephalitis virus vaccine
  • ketoconazole
  • lasmiditan
  • lovastatin
  • macimorelin
  • macitentan
  • measles (rubeola) vaccine
  • measles mumps and rubella vaccine, live
  • measles, mumps, rubella and varicella vaccine, live
  • meningococcal A C Y and W-135 polysaccharide vaccine combined
  • midostaurin
  • naldemedine
  • nefazodone
  • neratinib
  • netupitant/palonosetron
  • nivolumab
  • olaparib
  • osimertinib
  • palbociclib
  • perampanel
  • pneumococcal vaccine 13-valent
  • pneumococcal vaccine heptavalent
  • pneumococcal vaccine polyvalent
  • ponatinib
  • quinidine
  • rabies vaccine
  • rabies vaccine chick embryo cell derived
  • ranolazine
  • rifabutin
  • rifampin
  • rolapitant
  • romidepsin
  • rotavirus oral vaccine, live
  • rubella vaccine
  • silodosin
  • simeprevir
  • simvastatin
  • sirolimus
  • smallpox (vaccinia) vaccine, live
  • sofosbuvir/velpatasvir
  • sonidegib
  • squill
  • St John’s Wort
  • testosterone intranasal
  • tetanus toxoid adsorbed or fluid
  • tezacaftor
  • tick borne encephalitis vaccine
  • tisagenlecleucel
  • tofacitinib
  • tolvaptan
  • trabectedin
  • travelers diarrhea and cholera vaccine inactivated
  • tucatinib
  • typhoid polysaccharide vaccine
  • typhoid vaccine live
  • ulipristal
  • valbenazine
  • varicella virus vaccine live
  • vemurafenib
  • venetoclax
  • vorapaxar
  • voxelotor
  • yellow fever vaccine
  • zoster vaccine live

Monitor Closely

  • abiraterone
  • aceclofenac
  • acemetacin
  • albiglutide
  • alitretinoin
  • almotriptan
  • alprazolam
  • amiodarone
  • amobarbital
  • antithrombin alfa
  • antithrombin III
  • aprepitant
  • argatroban
  • aripiprazole
  • armodafinil
  • artemether/lumefantrine
  • aspirin
  • aspirin rectal
  • aspirin/citric acid/sodium bicarbonate
  • atazanavir
  • atorvastatin
  • atracurium
  • avanafil
  • bazedoxifene/conjugated estrogens
  • belatacept
  • bemiparin
  • benzhydrocodone/acetaminophen
  • bexarotene
  • bivalirudin
  • bortezomib
  • bosentan
  • bosutinib
  • brentuximab vedotin
  • brexpiprazole
  • budesonide
  • buprenorphine
  • buprenorphine buccal
  • buprenorphine subdermal implant
  • buprenorphine, long-acting injection
  • buspirone
  • butabarbital
  • butalbital
  • calcifediol
  • carbamazepine
  • celecoxib
  • cenobamate
  • cholera vaccine
  • cholestyramine
  • choline magnesium trisalicylate
  • cilostazol
  • cinacalcet
  • ciprofloxacin
  • cisatracurium
  • clarithromycin
  • clopidogrel
  • clotrimazole
  • clozapine
  • colchicine
  • conivaptan
  • conjugated estrogens
  • conjugated estrogens, vaginal
  • corticorelin
  • cortisone
  • crizotinib
  • crofelemer
  • cyclosporine
  • dabrafenib
  • dalteparin
  • darifenacin
  • darunavir
  • dasatinib
  • deferasirox
  • dengue vaccine
  • denosumab
  • DHEA, herbal
  • diazepam
  • dichlorphenamide
  • diclofenac
  • diflunisal
  • diltiazem
  • doxorubicin
  • doxorubicin liposomal
  • dronabinol
  • dronedarone
  • duvelisib
  • efavirenz
  • elagolix
  • eletriptan
  • eliglustat
  • elvitegravir/cobicistat/emtricitabine/tenofovir DF
  • encorafenib
  • enoxaparin
  • erlotinib
  • erythromycin base
  • erythromycin ethylsuccinate
  • erythromycin lactobionate
  • erythromycin stearate
  • eslicarbazepine acetate
  • estradiol
  • estradiol vaginal
  • estrogens conjugated synthetic
  • estrogens esterified
  • estropipate
  • ethotoin
  • etodolac
  • etoposide
  • etravirine
  • eucalyptus
  • exemestane
  • exenatide injectable solution
  • exenatide injectable suspension
  • fedratinib
  • felodipine
  • fenbufen
  • fenoprofen
  • fentanyl
  • fentanyl intranasal
  • fentanyl transdermal
  • fentanyl transmucosal
  • fesoterodine
  • fingolimod
  • flibanserin
  • fluconazole
  • fludrocortisone
  • flurbiprofen
  • fondaparinux
  • fosamprenavir
  • fosphenytoin
  • fostamatinib
  • gefitinib
  • gemifloxacin
  • glecaprevir/pibrentasvir
  • glycerol phenylbutyrate
  • grapefruit
  • griseofulvin
  • guanfacine
  • haemophilus influenzae type b vaccine
  • hemin
  • heparin
  • hydrocodone
  • hydrocortisone
  • hydroxyprogesterone caproate
  • ibuprofen
  • ibuprofen IV
  • ifosfamide
  • iloperidone
  • indacaterol, inhaled
  • indinavir
  • indomethacin
  • influenza A (H5N1) vaccine
  • influenza virus vaccine (H5N1), adjuvanted
  • influenza virus vaccine quadrivalent, recombinant
  • influenza virus vaccine trivalent, recombinant
  • insulin degludec
  • insulin degludec/insulin aspart
  • insulin inhaled
  • irinotecan
  • irinotecan liposomal
  • isoniazid
  • istradefylline
  • itraconazole
  • ivacaftor
  • ixabepilone
  • ketoconazole
  • ketoprofen
  • ketorolac
  • ketorolac intranasal
  • lapatinib
  • letermovir
  • levofloxacin
  • levonorgestrel intrauterine
  • levonorgestrel oral
  • levonorgestrel oral/ethinylestradiol/ferrous bisglycinate
  • liraglutide
  • lomitapide
  • lopinavir
  • loratadine
  • lornoxicam
  • lovastatin
  • lumefantrine
  • maraviroc
  • marijuana
  • meclofenamate
  • medroxyprogesterone
  • mefenamic acid
  • meloxicam
  • meningococcal group B vaccine
  • mestranol
  • methadone
  • methylprednisolone
  • metronidazole
  • miconazole vaginal
  • midazolam
  • mitotane
  • modafinil
  • moxifloxacin
  • nabumetone
  • naproxen
  • nefazodone
  • nelfinavir
  • nevirapine
  • nicardipine
  • nifedipine
  • nilotinib
  • nisoldipine
  • ocrelizumab
  • ofloxacin
  • olodaterol inhaled
  • ondansetron
  • ospemifene
  • oxaprozin
  • oxcarbazepine
  • oxiconazole
  • oxycodone
  • ozanimod
  • paclitaxel
  • paclitaxel protein bound
  • pancuronium
  • parecoxib
  • pazopanib
  • pentobarbital
  • phenindione
  • phenobarbital
  • phenytoin
  • pimavanserin
  • piroxicam
  • poliovirus vaccine inactivated
  • pomalidomide
  • ponatinib
  • posaconazole
  • prednisolone
  • prednisone
  • primidone
  • protamine
  • quercetin
  • quetiapine
  • quinidine
  • quinupristin/dalfopristin
  • ranolazine
  • repaglinide
  • ribociclib
  • rifampin
  • rifapentine
  • riociguat
  • ritonavir
  • rivaroxaban
  • rocuronium
  • rufinamide
  • salicylates (non-asa)
  • salsalate
  • saquinavir
  • sarecycline
  • secobarbital
  • selexipag
  • sildenafil
  • simvastatin
  • sipuleucel-T
  • sirolimus
  • sodium picosulfate/magnesium oxide/anhydrous citric acid
  • sodium sulfate/potassium sulfate/magnesium sulfate
  • sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol
  • solifenacin
  • somatrem
  • sorafenib
  • spironolactone
  • St John’s Wort
  • stiripentol
  • succinylcholine
  • sulfasalazine
  • sulindac
  • sunitinib
  • suvorexant
  • tacrolimus
  • tadalafil
  • tamoxifen
  • tasimelteon
  • tazemetostat
  • tecovirimat
  • temsirolimus
  • theophylline
  • ticagrelor
  • tinidazole
  • tipranavir
  • tofacitinib
  • tolfenamic acid
  • tolmetin
  • tolterodine
  • tolvaptan
  • topiramate
  • toremifene
  • tramadol
  • trastuzumab
  • trastuzumab deruxtecan
  • trazodone
  • triamcinolone acetonide injectable suspension
  • triazolam
  • tucatinib
  • ubrogepant
  • vardenafil
  • vecuronium
  • vemurafenib
  • verapamil
  • vilazodone
  • voriconazole
  • vortioxetine
  • warfarin
  • xipamide
  • zafirlukast
  • zoster vaccine recombinant

Minor

  • acarbose
  • albendazole
  • alfentanil
  • alfuzosin
  • alosetron
  • ambrisentan
  • amitriptyline
  • amlodipine
  • amphotericin B deoxycholate
  • armodafinil
  • aspirin
  • aspirin rectal
  • aspirin/citric acid/sodium bicarbonate
  • atazanavir
  • balsalazide
  • bendroflumethiazide
  • bosentan
  • bumetanide
  • calcium acetate
  • calcium carbonate
  • calcium chloride
  • calcium citrate
  • calcium gluconate
  • caspofungin
  • cevimeline
  • chlorothiazide
  • chlorpropamide
  • chlorthalidone
  • choline magnesium trisalicylate
  • chromium
  • clarithromycin
  • clomipramine
  • colestipol
  • cyclopenthiazide
  • cyclosporine
  • danazol
  • dapsone
  • desipramine
  • diflunisal
  • disopyramide
  • docetaxel
  • donepezil
  • dutasteride
  • efavirenz
  • eplerenone
  • esomeprazole
  • ethacrynic acid
  • eucalyptus
  • feverfew
  • finasteride
  • fluoxymesterone
  • furosemide
  • galantamine
  • glimepiride
  • glipizide
  • glyburide
  • hydrochlorothiazide
  • imatinib
  • imipramine
  • indapamide
  • insulin aspart
  • insulin detemir
  • insulin glargine
  • insulin glulisine
  • insulin lispro
  • insulin NPH
  • insulin regular human
  • isoniazid
  • isradipine
  • ketoconazole
  • lansoprazole
  • mesalamine
  • mesterolone
  • metformin
  • methyclothiazide
  • methyltestosterone
  • metolazone
  • metyrapone
  • miglitol
  • montelukast
  • nateglinide
  • nimodipine
  • nitrendipine
  • omeprazole
  • oxandrolone
  • oxybutynin
  • oxymetholone
  • paclitaxel
  • paclitaxel protein bound
  • pantoprazole
  • parecoxib
  • pimozide
  • pioglitazone
  • porfimer
  • propafenone
  • quinine
  • rabeprazole
  • ramelteon
  • repaglinide
  • rosiglitazone
  • salicylates (non-asa)
  • salsalate
  • sargramostim
  • saxagliptin
  • sitagliptin
  • somatropin
  • sufentanil
  • sulfasalazine
  • tacrolimus
  • testosterone
  • testosterone buccal system
  • testosterone topical
  • tolazamide
  • tolbutamide
  • torsemide
  • troleandomycin
  • vesnarinone
  • vildagliptin
  • vinblastine
  • vincristine
  • vincristine liposomal
  • vinorelbine
  • willow bark
  • zaleplon
  • ziprasidone
  • zolpidem
  • zonisamide

Adverse Effects

  • Allergic reactions: Anaphylactoid reaction, anaphylaxis, angioedema
  • Cardiovascular: Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, fat embolism, hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction, edema, pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis
  • Dermatologic: Acne, allergic dermatitis, dry scaly skin, ecchymoses and petechiae, erythema, impaired wound healing, increased sweating, rash, striae, suppression of reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria
  • Endocrine: Decreased carbohydrate and glucose tolerance, development of the cushingoid state, hyperglycemia, glycosuria, hirsutism, hypertrichosis, increased requirements for insulin or oral hypoglycemic agents in diabetes, manifestations of latent diabetes mellitus, menstrual irregularities, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery, or illness), suppression of growth in pediatric patients
  • Fluid and electrolyte disturbances: Congestive heart failure in susceptible patients, fluid retention, hypokalemic alkalosis, potassium loss, sodium retention, tumor lysis syndrome
  • Gastrointestinal: Abdominal distention, elevation in serum liver enzyme levels (usually reversible upon discontinuation), hepatomegaly, increased appetite, nausea, pancreatitis, peptic ulcer with possible perforation and hemorrhage, perforation of the small and large intestine (particularly in patients with inflammatory bowel disease), ulcerative esophagitis
  • Metabolic: Negative nitrogen balance due to protein catabolism
  • Musculoskeletal: Aseptic necrosis of femoral and humeral heads, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, steroid myopathy, tendon rupture, vertebral compression fractures
  • Neurological/Psychiatric: Convulsions, depression, emotional instability, euphoria, headache, increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment, insomnia, mood swings, neuritis, neuropathy, paresthesia, personality changes, psychic disorders, vertigo
  • Ophthalmic: Exophthalmos, glaucoma, increased intraocular pressure, posterior subcapsular cataracts, vision blurred
  • Other: Abnormal fat deposits, decreased resistance to infection, hiccups, increased or decreased motility and number of spermatozoa, malaise, moon face, weight gain

Warnings

Contraindications

  • Systemic fungal infection
  • Documented hypersensitivity
  • Cerebral malaria
  • Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids

Cautions

  • Use with caution in cirrhosis, diverticulitis, myasthenia gravis, peptic ulcer disease, ulcerative colitis, renal insufficiency, pregnancy
  • Average and large doses of corticosteroids can cause elevation of blood pressure, sodium and water retention, and increased excretion of potassium; these effects are less likely to occur with synthetic derivatives except when used in large doses; dietary salt restriction and potassium supplementation may be necessary; all corticosteroids increase calcium excretion
  • Corticosteroids can produce reversible hypothalamic-pituitary adrenal (HPA) axis suppression with potential for glucocorticosteroid insufficiency after withdrawal of treatment; adrenocortical insufficiency may result from too rapid withdrawal; may be minimized by gradual reduction of dosage; relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, reinstitute hormone therapy; if patient is receiving steroids already, may increase dosage
  • Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients; changes in thyroid status of patient may necessitate adjustment in dosage
  • May exacerbate systemic fungal infections
  • Latent disease may be activated or there may be an exacerbation of intercurrent infections due to pathogens, including those caused by Amoeba, Candida, Cryptococcus, Mycobacterium, Nocardia, Pneumocystis, toxoplasma; rule out latent amebiasis or active amebiasis before initiating corticosteroid therapy in any patient who has spent time in the tropics or any patient with unexplained diarrhea
  • Use with great care in patients with known or suspected Strongyloides (threadworm) infestation; corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia; not for use in cerebral malaria
  • Close observation necessary if corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity; reactivation of the disease may occur; during prolonged corticosteroid therapy, these patients should receive chemoprophylaxis
  • Use of oral corticosteroids not recommended in treatment of optic neuritis and may lead to increase in risk of new episodes; corticosteroids should not be used in active ocular herpes simplex
  • Use lowest possible dose to control condition under treatment; risk/benefit decision must be made in each individual case as to dose and duration of treatment and as to whether daily or intermittent therapy should be used
  • May lead to inhibition of bone growth in pediatric patients and development of osteoporosis at any age; special consideration should be given to patients at increased risk of osteoporosis (e.g., postmenopausal women) before initiating corticosteroid therapy
  • Psychic derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychotic manifestations; existing emotional instability or psychotic tendencies may also be aggravated by corticosteroids
  • Thromboembolic disorders
  • Myopathy has been reported
  • Delayed wound healing
  • If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated; if exposed to measles, prophylaxis with immune globulin (IG) may be indicated; if chickenpox develops, treatment with antiviral agents should be considered
  • Latent tuberculosis may be reactivated (patients with positive tuberculin test should be monitored)
  • Some suggestion (not fully substantiated) of slightly increased cleft palate risk if corticosteroids are used in pregnancy
  • Prolonged corticosteroid use may result in elevated intraocular pressure, glaucoma, or cataracts with possible damage to optic nerves, and may enhance establishment of secondary ocular infections due to bacteria, fungi, or viruses; consider referral to ophthalmologist for patients who develop ocular symptoms or use corticosteroid-containing products for more than 6 weeks
  • Prolonged therapy has been associated with development of Kaposi sarcoma
  • May affect velocity growth in children; monitor routinely
  • Immunization procedures may be undertaken in patients who are receiving corticosteroids as replacement therapy in physiologic doses (eg, for Addison’s disease)

Epidural injection

  • Serious neurologic events, some resulting in death, have been reported with epidural injection
  • Specific events reported include, but are not limited to, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke
  • These serious neurologic events have been reported with and without use of fluoroscopy
  • Safety and effectiveness of epidural administration of corticosteroids have not been established, and corticosteroids are not approved for this use

Drug interaction overview

  • Strong CYP3A4 inhibitors: Coadministration of strong and moderate CYP3A4 inhibitors increased dexamethasone exposure, which may increase the risk of adverse reactions
  • Strong CYP3A4 inducers: Coadministration of strong CYP3A4 inducers may decrease dexamethasone exposure, which may result in loss of efficacy
  • Cholestyramine: Cholestyramine may increase clearance of corticosteroids and potentially decrease corticosteroid exposure
  • Anticholinesterases: Concomitant use of anticholinesterase agents and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hr before initiating corticosteroid therapy
  • Ephedrine: Ephedrine may decrease dexamethasone exposure and may result in loss of efficacy. Consider increasing the dexamethasone dose when used with ephedrine
  • Estrogens: Estrogens may decrease the hepatic metabolism of certain corticosteroids and increase exposures, which may increase the risk of adverse reactions
  • CYP3A4 substrates: Coadministration of dexamethasone with substrates may decrease the concentration of these drugs, resulting in loss of efficacy of these drugs
  • Oral anticoagulants: Coadministration of anticoagulants with corticosteroids may reduce the response to anticoagulants; frequently monitor coagulation indices to maintain the desired anticoagulant effect
  • Amphotericin B injection and potassium-depleting agents: Sodium retention with resultant edema and potassium loss may occur in patients receiving corticosteroid; closely monitor potassium levels
  • Antidiabetics: Corticosteroids may increase blood glucose concentrations; consider adjusting the dose of antidiabetic agents, as necessary
  • Isoniazid: Serum concentrations of isoniazid may be decreased with corticosteroids
  • Cyclosporine: Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with this concurrent use
  • Digitalis glycosides: Patients on digitalis glycosides may be at increased risk of arrhythmias due to hypokalemia
  • Nonsteroidal Anti-Inflammatory Agents (NSAIDS): Concomitant use of aspirin (or other NSAIDS) and corticosteroids increases the risk of gastrointestinal side effects; clearance of salicylates may be increased with concurrent use of corticosteroids; monitor for toxicity
  • Phenytoin: Reports of both increases and decreases in phenytoin levels with dexamethasone coadministration, leading to alterations in seizure control
  • Vaccines: Patients on corticosteroid therapy may exhibit a diminished response to toxoids and live or inactivated vaccines due to inhibition of antibody response. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines. If possible, defer routine administration of vaccines or toxoids until therapy is discontinued
  • Concomitant therapies that may increase the risk of thromboembolism: Erythropoietic agents, or other agents that may increase the risk of thromboembolism, such as estrogen containing therapies, coadministered with dexamethasone may increase the risk of thromboembolism; monitor for risk of thromboembolism
  • Thalidomide: Toxic epidermal necrolysis has been reported with concomitant use of thalidomide. Closely monitor for toxicity
  • Skin tests: Corticosteroids may suppress reactions to skin tests

Safety Advice

🍺   Alcohol: Caution

🤰🏻   Pregnancy: Category C

🤱🏻   Breastfeeding: Unsafe

🚗   Driving: Safe

 Kidney: Safe

 Liver: Caution

 

 

 

 

 

 

 

 

Pharmacology

Mechanism of Action: Decreases inflammation by suppressing migration of polymorphonuclear leukocytes (PMNs) and reducing capillary permeability; stabilizes cell and lysosomal membranes, increases surfactant synthesis, increases serum vitamin A concentration, and inhibits prostaglandin and proinflammatory cytokines; suppresses lymphocyte proliferation through direct cytolysis, inhibits mitosis, breaks down granulocyte aggregates, and improves pulmonary microcirculation

Absorption

Onset: Between a few minutes and several hours; dependent on indication and route of administration

Peak serum time: 8hr (IM); 1-2 hr (PO)

Distribution: Vd: 2 L/kg

Metabolism: Metabolized in liver

Elimination: Half-life: 1.8-3.5 hr (normal renal function)

Excretion: Urine (mainly), feces (minimally)

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Tenofovir prophylaxis to prevent mother-to-child transmission of HBV

New recommendation: WHO recommends that pregnant women testing positive for HBV infection (HBsAg positive) with an HBV DNA ≥ 5.3 log10 IU/mL (≥ 200,000 IU/mL)1 receive tenofovir prophylaxis from the 28th week of pregnancy until at least birth, to prevent mother-to-child transmission of HBV. This is in addition to three-dose hepatitis B vaccination in all infants, including timely birth dose (conditional recommendation, moderate quality of evidence). Use of HBeAg testing, where HBV DNA testing is not available, to determine treatment eligibility for tenofovir prophylaxis to prevent mother-to-child transmission of HBV.

New recommendation: WHO recommends that in settings in which antenatal HBV DNA testing is not available, HBeAg testing can be used as an alternative to HBV DNA testing to determine eligibility for tenofovir prophylaxis to prevent mother-to-child transmission of HBV2 (conditional
recommendation, moderate quality of evidence).

Source: WHO

Lenvatinib-Pembrolizumab combination in Advanced Gastric Cancer

The combination of the anti-PD-1 antibody pembrolizumab and the multikinase inhibitor lenvatinib provides objective response rates in many patients with advanced gastric cancer, according to results from an early single-arm trial.

Lenvatinib monotherapy was associated with durably stable disease in a phase-1 study of patients with solid tumors, and the combination of lenvatinib plus pembrolizumab has shown promising antitumor activity with manageable safety profiles for several malignancies.

Lenvatinib is a multikinase inhibitor of VEGFR1, VEGFR2, and VEGFR3, and other receptor tyrosine kinases. Pembrolizumab, an antibody targeting PD-1, has also moderate efficacy in biomarker-unselected endometrial cancer.

Source: Medscape

Zinc 24 Hours Urine Test

Uses: Identifying the cause of abnormal serum zinc concentrations using a 24-hour urine specimen. Useful as an indicator of acute toxicity. May be useful as an indicator of deficiency in conjunction with Zinc, Serum or Plasma

Method: Quantitative Inductively Coupled Plasma-Mass Spectrometry (ICPMS)

Category: Endocrinology

Reference:

Test Number Components Reference Interval
Zinc, Urine 15.0-120.0 µg/dL
Zinc, Urine-per 24h 150.0-1200.0 µg/d
Zinc, Urine-ratio to CRT 110.0-750.0 µg/gCRT
Creatinine, Urine – per 24h
Age Male Female
3-8 years 140-700 mg/d 140-700 mg/d
9-12 years 300-1300 mg/d 300-1300 mg/d
13-17 years 500-2300 mg/d 400-1600 mg/d
18-50 years 1000-2500 mg/d 700-1600 mg/d
51-80 years 800-2100 mg/d 500-1400 mg/d
81 years and older 600-2000 mg/d 400-1300 mg/d

Pre-test Information:

  • Patients should be encouraged to discontinue nutritional supplements, vitamins, minerals, and non-essential over-the-counter medications (upon the advice of their physician)
  • Collection from patients receiving iodinated or gadolinium-based contrast media must be avoided for a minimum of 72 hours post-exposure
  • High concentrations of barium are known to interfere with this test. If barium-containing contrast media has been administered, a specimen should not be collected for 96 hours.
  • Collection from patients with impaired kidney function should be avoided for a minimum of 14 days post contrast media exposure.
  • Patients should avoid sea/fresh water fish 3 days prior to specimen collection

Specimen Collection: 24 hour urine specimen must be collected in a plastic container. 10 mL (5 mL min.) aliquot of 24 hour urine collected in acid washed (metal free) container kit available. Mix thoroughly. Transfer 10 mL aliquot to vial provided in the kit. Measure 24 hour total volume and record on vial and test request form

Storage: Refrigerated, Room temperature or frozen

Stability: Stability Room 24 hrs
Stability Refrigerated 48 hrs
Stability Frozen 1 week

Report Availability: 1-5 days

More Details: Zinc is an essential element which acts as a critical co-factor in various enzyme systems and is required for active wound healing. Zinc deficiency occurs due to lack of dietary absorption or loss after absorption. Zinc excess is not a major clinical concern. The only known effect of excessive zinc ingestion is interference with copper absorption leading to hypocupremia. This assay is useful for identifying the cause of abnormal serum zinc. Fecal excretion of zinc is the dominant route of elimination. Renal excretion is a minor, secondary elimination pathway. Normal daily excretion of zinc in the urine is in the range of 20 to 967 mcg/24 hours. High urine zinc associated with low serum zinc may be caused by hepatic cirrhosis, neoplastic disease, or increased catabolism. High urine zinc with normal or elevated serum zinc indicates a large dietary source, usually in the form of high-dose vitamins. Low urine zinc with low serum zinc may be caused by dietary deficiency or loss through exudation common in burn patients and those with gastrointestinal losses

COVID-19 coronavirus vaccine tracker

Researchers worldwide are working around the clock to find a vaccine against SARS-CoV-2, the virus causing the COVID-19 pandemic. Experts estimate that a fast-tracked vaccine development process could speed a successful candidate to market in approximately 12-18 months.

How are vaccines tested?

  • In the pre-clinical stage of testing, researchers give the vaccine to animals to see if it triggers an immune response.
  • In phase 1 of clinical testing, the vaccine is given to a small group of people to determine whether it is safe and to learn more about the immune response it provokes.
  • In phase 2, the vaccine is given to hundreds of people so scientists can learn more about its safety and correct dosage.
  • In phase 3, the vaccine is given to thousands of people to confirm its safety – including rare side effects – and effectiveness. These trials involve a control group which is given a placebo.

Vaccines in clinical trials

  • Sinovac: Chinese company Sinovac is developing a vaccine based on inactivated Covid-19 particles. The vaccine has shown a promising safety profile in the early stages of testing and is now moving into Phase 3 trials in Brazil.
  • The Murdoch Children’s Research Institute in Australia is conducting a phase 3 trial using a nearly 100-year-old tuberculosis vaccine. The vaccine is not thought to protect directly against Covid-19 but might boost the body’s non-specific immune response.
  • University of Oxford/AstraZeneca: The University of Oxford vaccine is delivered via a chimpanzee virus, called the vaccine vector. The vector contains the genetic code of the protein spikes found on the coronavirus and triggers a strong immune response in the human body. The vaccine is in a combined phase 2/3 trial in the UK and has recently gone into phase 3 trials in South Africa and Brazil.
    CanSino Biologics Inc./Beijing Institute of Biotechnology
    The vaccine developed by Chinese company CanSino Biologics and the Beijing Institute of Biotechnology – a university close to the Chinese military – reportedly showed promising results in phase 2 testing, although no data from the trial has been published. In a world first, the vaccine has now been approved for military use, but it is unclear how broadly it will be distributed.
  • Moderna/NIAID: American biotech company Moderna is developing a vaccine candidate using messenger RNA (or mRNA for short) to trick the body into producing viral proteins itself. No mRNA vaccine has ever been approved for an infectious disease, and Moderna has never brought a product to market. But proponents of the vaccine say it could be easier to mass produce than traditional vaccines.
  • Inovio Pharmaceuticals/ International Vaccine Institute
  • Cadila Healthcare Limited
  • Wuhan Institute of Biological Products/Sinopharm
  • Beijing Institute of Biological Products/Sinopharm
  • Novavax
  • BioNTech/Fosun Pharma/Pfizer
  • Genexine Consortium
  • Osaka University/ AnGes/ Takara Bio
  • Institute of Medical Biology, Chinese Academy of Medical Sciences
  • Gamaleya Research Institute
  • Clover Biopharmaceuticals Inc./GSK/Dynavax
  • Anhui Zhifei Longcom Biopharmaceutical/ Institute of Microbiology,
  • Chinese Academy of Sciences
  • Vaxine Pty Ltd/Medytox
  • Imperial College London
  • Curevac
  • People’s Liberation Army (PLA) Academy of Military Sciences/Walvax Biotech.
  • Medicago Inc./ Université Laval
  • University of Melbourne/Murdoch Children’s Research Institute

Draft landscape of COVID-19 candidate vaccines by WHO: Download PDF ›

Source: WHO

FDA approves Collagenase Clostridium Histolyticum for Cellulite

The FDA has approved collagenase clostridium histolyticum for the treatment of moderate to severe cellulite in the buttocks of adult women. The drug is the first injectable treatment for cellulite to receive regulatory approval.

Dose: 0.9mg Solution, Injection

MOA: When injected into the treatment area, It is thought to release the fibrous septae enzymatically by specifically targeting types 1 and 3 collagen, which may result in the smoothing of the skin and an improved appearance of cellulite.

Common side effects: Injection site bruising, pain, areas of hardness, itching, redness, discoloration, swelling, and warmth in the treatment area.

In cellulite, fibrous septae are a primary contributing factor. The septae make up the fibrous connective tissue that connects the skin perpendicularly to the fascia below and tether the skin, drawing it downward and leading to a mattress-like appearance, commonly referred to as “dimpling.”

Cutaneous manifestations of COVID-19

Observed COVID-19 associated skin patterns were:

  • Acral erythema with vesicles or pustules; so-called “pseudo-chilblains”  or “COVID Toes” (19%)
  • Vesicular (chicken pox-like) eruptions (9%)
  • Maculopapular eruptions (47%)
  • Urticaria (19%)
  • Livedo or necrosis (6%)

1. Acral areas of erythema-oedema with some vesicles or pustules (pseudo-chilblain) (19% of cases).

These lesions, affecting hands and feet, may resemble chilblains (small, itchy swellings on the skin) with small red or purple spots, caused by bleeding under the skin. They were usually asymmetrical.

Associated with: younger patients, lasted for a mean of 12.7 days, took place later in the course of the COVID-19 disease and was associated with less severe disease (in terms of hospital admission, pneumonia, intensive care unit admission or mortality). They could cause pain (32%) or itch (30%).

2. Other vesicular eruptions (9%).

Vesicular eruptions are outbreaks of small blisters, some of these presented on the trunk. They may also affect the limbs, may be filled with blood, and become larger or more spread out.

Associated with: middle aged patients, lasted for a mean of 10.4 days, appeared more commonly (15%) before other symptoms and were associated with intermediate severity. Itching was common (68%).

3. Urticarial lesions (19%):

These consist of pink or white raised areas of skin resembling nettle rash, known as wheals (also spelled weals), which are usually itchy. Mostly distributed in the trunk or spread across the body. A few cases were on the palms of the hands. Associated with: see below ‘4. Other maculopapules’

4. Other maculopapules (47%).

Maculopapules are small, flat and raised red bumps. In some cases these were distributed around hair follicles, there was also varying degrees of scaling. Some had been described as similar to pityriasis rosea, a common skin condition. Blood spots under the skin may also be present, either in the form of spots/dots or on larger areas.

Associated with: lasting for a shorter period (6.8 days mean for urticarial and 8.6 for maculopapular), usually appeared at the same time than the rest of the symptoms and were associated with more severe COVID-19 disease (2% mortality in the sample). Itching was very common for urticariform lesions (92%) and 57% for maulopapular.

5. Livedo or necrosis (6%).

Livedo is a skin condition where circulation in the blood vessels of the skin is impaired. It causes the skin to take on a blotchy red or blue appearance with a retiform (net-like) pattern. Necrosis refers to the premature death of skin tissue. These patients showed different degrees of lesions suggesting occlusive vascular disease, where a narrowing or blocking of arteries occurs, limiting blood flow to certain areas of the body (in this case the trunk or extremities).

Associated with: older patients with more severe disease (10% mortality). However, the manifestations of COVID-19 in this group were more variable, including transient livedo, with some suffering COVID-19 that did not require hospitalisation.

Source: Medscape, skinhealthinfo.org.uk

Triple therapy for COPD

Triple fixed-dose regimens of an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β2-agonist (LABA) for chronic obstructive pulmonary disease (COPD) have been studied at single-dose levels of inhaled glucocorticoid, but studies at two dose levels are lacking.

Triple therapy with twice-daily budesonide (at either the 160-μg or 320-μg dose), glycopyrrolate, and formoterol resulted in a lower rate of moderate or severe COPD exacerbations than glycopyrrolate–formoterol or budesonide–formoterol.

Case study: The modified intention-to-treat population comprised of 8509 patients. The annual rates of moderate or severe exacerbations were 1.08 in the 320-μg–budesonide triple-therapy group (2137 patients), 1.07 in the 160-μg–budesonide triple-therapy group (2121 patients), 1.42 in the glycopyrrolate–formoterol group (2120 patients), and 1.24 in the budesonide–formoterol group (2131 patients). The rate was significantly lower with 320-μg–budesonide triple therapy than with glycopyrrolate–formoterol (24% lower: rate ratio, 0.76; 95% confidence interval [CI], 0.69 to 0.83; P<0.001) or budesonide–formoterol (13% lower: rate ratio, 0.87; 95% CI, 0.79 to 0.95; P=0.003). Similarly, the rate was significantly lower with 160-μg–budesonide triple therapy than with glycopyrrolate–formoterol (25% lower: rate ratio, 0.75; 95% CI, 0.69 to 0.83; P<0.001) or budesonide–formoterol (14% lower: rate ratio, 0.86; 95% CI, 0.79 to 0.95; P=0.002). The incidence of any adverse event was similar across the treatment groups (range, 61.7 to 64.5%); the incidence of confirmed pneumonia ranged from 3.5 to 4.5% in the groups that included inhaled glucocorticoid use and was 2.3% in the glycopyrrolate–formoterol group

Source: NEJM.org

Fostemsavir

Rx Prescription Required

Classes: Antiretroviral Agents, gp120 attachment inhibitor, Pyridines & derivatives

Uses: Multidrug-resistant HIV-1 infection 

Administration: Oral (600 mg extended-release tablets)

Dosages ›
Interactions ›
Adverse Effects ›
Warnings ›
Safety Advice ›
Pharmacology ›
General Considerations ›
Monitoring Parameters ›

Rukobia

Manufacturer: ViiV Healthcare Ltd (majority-owned by GlaxoSmithKline, with Pfizer & Shionogi as shareholders)

Salt Composition: Fostemsavir (600mg)

Price: NA

No drug combination found

Dosages

HIV-1 Infection

  • 600mg BD in combination with other antiretrovirals
  • It is indicated for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations
  • The extended-release tablet contains 600 mg of fostemsavir (equivalent to 725 mg of fostemsavir tromethamine)

The safety and effectiveness of Fostemsavir have not been established in pediatric patients

Interactions

Contraindicated

  • Enzalutamide
  • Carbamazepine
  • Phenytoin
  • Rifampin
  • MitotaneSt John’s wort (Hypericum perforatum)

Serious

  • Grazoprevir
  • Voxilaprevir

Monitor Closely

  • Ethinyl estradiol
  • Rosuvastatin
  • Atorvastatin
  • Fluvastatin
  • Pitavastatin
  • Simvastatin

Adverse Effects

  • Nausea 10%
  • Diarrhoea 4%
  • Headache 4%
  • Abdominal pain 3%
  • Dyspepsia 3%
  • Fatigued 3%
  • Rash 3%
  • Sleep disturbance 3%
  • Immune Reconstitution Inflammatory Syndrome 2%
  • Somnolence 2%
  • Vomiting 2%
  • Elevations in hepatic transaminases in patients with hepatitis B or C virus co-infection: Elevations in hepatic transaminases were observed in a greater proportion of subjects with HBV and/or HCV co-infection compared with those with HIV mono-infection.
  • Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions: The concomitant use of fostemsavir and certain other drugs may result in known or potentially significant drug interactions, some of which may lead to 1) Loss of therapeutic effect of fostemsavir and possible development of resistance due to reduced exposure of temsavir 2) Possible prolongation of QTc interval from increased exposure to temsavir.

Less common adverse reactions

  • Cardiac Disorders: Electrocardiogram QT prolonged, Torsade de Pointes
  • Musculoskeletal Disorders: Myalgia.
  • Nervous System Disorders: Dizziness, dysgeusia, neuropathy peripheral (includes pooled terms: neuropathy peripheral and peripheral sensory neuropathy).
  • Skin and Subcutaneous Tissue Disorders: Pruritus.

Contraindications & Warnings

Immune Reconstitution Syndrome

  • Immune reconstitution syndrome has been reported in patients. During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.
  • Autoimmune disorders (such as Graves’ disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable and can occur many months after initiation of treatment

QTc Prolongation

  • Seen with higher than recommended dosages at 2,400 mg twice daily, 4 times the recommended daily dose, has been shown to significantly prolong the QTc interval of the electrocardiogram

Safety Advice

🍺   Alcohol: Caution

🤰🏻   Pregnancy: Insufficient human data

🤱🏻   Breastfeeding: Unsafe

🚗   Driving: Safe

 Kidney: Safe

 Liver: Safe

 

Pharmacology

Mechanism of Action

  • Fostemsavir tromethamine is a prodrug of temsavir is a first-in-class HIV-1 attachment inhibitor. After oral administration, fostemsavir is converted to temsavir, which is then absorbed and exerts antiviral activity by attaching directly to the glycoprotein 120 (gp120) subunit on the surface of the virus, thereby blocking HIV from attaching to host immune system CD4+ T-cells and preventing the virus from infecting those cells and multiplying. As fostemsavir is the first antiretroviral therapy to target this step of the viral cycle, there is no demonstrated resistance to other classes of antiretrovirals, which may help patients who have become resistant to most other medicines.

About Temsavir

  • Temsavir  is a substrate of CYP3A, esterases, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP).
  • Coadministration of fostemsavir with drugs that are strong CYP3A inducers result in decreased concentrations of temsavir.
  • Coadministration of fostemsavir with drugs that are moderate CYP3A inducers and/or strong CYP3A, P-gp and/or BCRP inhibitors are not likely to have a clinically relevant effect on the plasma concentrations of temsavir. Temsavir is an inhibitor of OATP1B1 and OATP1B3.

Pharmacokinetic properties of Temsavir

  • Absolute bioavailability: 26.9%
  • Distribution: Plasma protein binding 88.4%
  • Major route of elimination: Metabolism
  • Half-life: 11 hours
  • Metabolic pathwayse: Hydrolysis (esterases) [36.1% of oral dose], Oxidation (CYP3A4) [21.2% of oral dose], UGT [<1% of oral dose]
  • Excretion: Urine (unchanged drug) 51 %, feces (unchanged drug) 33%, bile 5%

General Considerations

  • Advise the patient to read the FDA-approved patient labeling (Patient Information).
  • Hypersensitivity Reactions
  • Immune Reconstitution Syndrome: Advice patients to inform their healthcare provider immediately of any signs and symptoms of
    infection, as inflammation from the previous infection, may occur soon after combination antiretroviral therapy, including when fostemsavir is started
  • QTc Interval Prolongation: Advise patients that it may produce changes in their electrocardiogram (i.e., QT prolongation). Instruct patients to consult their healthcare provider if they experience symptoms such as dizziness, lightheadedness, abnormal heart rhythm, or loss of consciousness
  • Patients with Hepatitis B or C Virus Co-infection: Advise patients that it is recommended to have laboratory testing and to take medications for
    HBV or HCV as prescribed
  • Drug Interactions: Fostemsavir may interact with other drugs; therefore, advise patients to report to their healthcare provider the use of any other prescription or nonprescription medication or herbal products,
    including St. John’s wort
  • Pregnancy Registry: Inform patients that there is an antiretroviral pregnancy registry to monitor fetal outcomes in those exposed to fostemsavir during pregnancy.
  • Instruct mothers with HIV-1 infection not to breastfeed because HIV-1 can be passed to the baby in the breast milk
  • Potential Odor of Tablets: Tablets may have a slight vinegar-like odour
  • Missed Dosage: Advise patients to avoid missing doses as it can result in the development of resistance. Instruct patients that if they miss a dose of fostemsavir, to take it as soon as they remember. Advise
    patients not to double their next dose or take more than the prescribed dose

General Monitoring Parameters

  • ECG for estimation of QT interval
  • CBC at baseline with periodic tests for liver function, renal function, blood glucose level
  • CD4 count

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error: