WELLINGTON REGIONAL HOSPITAL INTENSIVE CARE UNIT DRUG MANUAL second edition 2013 Written by Paul Young second edition edited by Alex Psirides Intensive Care Specialists Wellington, New Zealand © 2013 Our page on facebook https://www.facebook.com/pages/Freemedicalbooks2014/657771750943967 http://freemedicalbooks2014.blogspot.com/ ! References used for all drug monographs are as follows: ! ! Fink, Mitchell et al http://www.criticalcaretext.com/content/drugdb/default.cfm Textbook of Critical Care 5th edition 2005 ! ! ! ! ! Ashley, Caroline and Currie, Aileen The Renal Drug Handbook 2nd ed United Kingdom: Radcliffe Medical Press Ltd, 2004 ! ! McClintock, Alan et al Notes on Injectable Drugs 5th ed New Zealand New Zealand Healthcare Pharmacists’ Association, 2004 ! ! Medsafe Drug Data sheets (New Zealand Medicine and Medical Devices Safety Authority): http://www.medsafe.govt.nz/profs/Datasheet/dsform.asp ! MIMS Online: http://www.mimsonline.co.nz/Default.aspx Shann, Frank Drug Doses 14th ed Intensive Care Unit Royal Children’s Hospital, Parkville, Victoria 3052, Australia, 2008 An online version of this drug manual, optimised for smartphone & tablet viewing, is available at: http://drug.wellingtonicu.com/ An offline version is available for download (as a PDF) from: http://www.wellingtonicu.com/Forms/ The most up-to-date version of this drug manual will always be available online Should any discrepancies exist between the printed version & those available online, the latter should always take precedence Preface The first edition of the Intensive Care Drug Manual was developed by Dr.Paul Young for use in the Intensive Care Unit in Wellington Regional Hospital in 2011 This second edition was updated in 2013 with revisions made reflecting the changes in our unit’s Intensive Care practice On occasion, doses, methods of administration and indications differ from those available given in the product information In such cases, recommendations reflect common ICU practice both here and elsewhere All doses have been checked independently by two Intensive Care Specialists However, if you suspect an error is present, please check data with alternative sources and notify the editor Clinical responsibility remains with the prescribing doctor Specific changes for the second edition include: • The monograph for recombinant activated protein C (Drotrecogin alfa/ Xigris) has been removed • Entries for Iloprost, Levosimendan & Tobramycin have been added • Appendices have been added to provide more information on common drug-related queries • Gentamicin dosage & monitoring has been changed • All drug prices quoted are in New Zealand dollars & are up to date as of January 2013 Prices have been included to inform prescribing choices where intravenous or enteral routes of administration are equivocal For example, the intravenous preparation of Acetazolamide costs 250 times that of a single tablet (bioavailability >90%) Paul Young Alex Psirides February 2013 alex.psirides@ccdhb.org.nz wellingtonicu.com This document (c) 2013 Wellington ICU It cannot be sold or altered without permission of the author A T A B L E O F C O N T E N T S Acetazolamide Acetylcysteine Acyclovir Adenosine Adrenaline Allopurinol Aminophylline Amiodarone Amitriptylline Amlodipine Amoxicillin / Amoxycillin Amoxicillin-Clavulanic Acid Amophtericin B (Liposomal) Aspirin Atenolol Atorvastatin Atracurium Atropine Azathioprine 11 14 17 20 23 26 29 31 33 36 39 42 44 46 48 50 52 B Bendrofluazide Benzylpenicillin / Penicillin G 55 57 C Caffeine Calcitriol Calcium Carbonate Calcium Chloride Calcium Gluconate Candesartan Captopril Carbamazepine Carvedilol Caspofungin Cefaclor Cefazolin / Cephazolin Cefotaxime 60 62 64 66 68 70 72 75 79 82 85 88 91 Ceftazidime Ceftriaxone Cefuroxime Celiprolol Charcoal (Activated) Chloral Hydrate Chlorpromazine Cilazapril Ciprofloxacin Citalopram Clarithromycin Clindamycin Clonazepam Clonidine Clopidogrel Clozapine Codeine Phosphate Colchicine Coloxyl with Senna Co-trimoxazole Cyclizine Cyclosporin 94 97 100 104 106 108 110 113 116 120 122 125 128 131 133 135 138 140 142 143 147 149 D Dantrolene DDAVP / Desmopressin Dexamethasone Sodium Phosphate Dexmedetomidine Diazepam Diclofenac Sodium Digoxin Diltiazem Dipyridamole Dobutamine Dopamine Doxazosin 154 156 158 161 163 166 170 174 177 179 181 184 E Enalapril Enoxaparin Ephedrine Erythromycin Esmolol Etomidate 186 189 193 195 198 200 F Felodipine Fentanyl Flucloxacillin Fluconazole Flumazenil Fluoxetine Frusemide L 202 204 206 209 212 214 216 Ibuprofen Iloprost Imipenem with Cilastatin Ipratropium Bromide Isoprenaline Hydrochloride 247 250 253 256 258 K Ketamine 260 C O N T E N T S I Magnesium Sulphate 277 Meropenem 280 Metaraminol 283 Metformin 285 Methylene Blue 287 Methylprednisolone Sodium Succinate 289 Metoclopramide 292 Metoprolol 295 Metronidazole 297 Midazolam 300 Milrinone 303 Morphine Sulphate & Morphine Tartrate 305 Moxifloxacin 308 O F 232 235 238 240 243 247 T A B L E 219 221 223 226 228 230 H Haloperidol Heparin Hydralazine Hydrocortisone Hyoscine Butylbromide Hyoscine Hydrobromide 262 265 267 270 273 275 M G Gabapentin Ganciclovir Gentamicin Glucagon Glyceryl Trinitrate Glycopyrrolate Labetalol Lactulose Levosimendan Lithium Loperamide Losartan N Naloxone Neostigmine Nicotine Nimodipine Noradrenaline 311 313 315 317 319 O Octreotide Olanzapine Omeprazole Ondansetron Oxycodone 321 323 325 327 329 P T A B L E Paracetamol Paracoxib Paroxetine Pethidine Hydrochloride Phenobarbitone Phenylephrine Phenytoin Potassium Chloride Phosphate Prednisone Propofol Propranolol Protamine Sulfate T 332 334 336 338 341 344 346 349 351 353 355 357 359 O F 416 420 422 424 361 C O N T E N T S W R Ranitidine Remifentanil Risperidone Rocuronium Roxithromycin 396 399 401 403 406 408 410 414 V Vancomycin Vasopressin Vitamin K Verapamil Q Quinapril Tazocin (Piperacillin & Tazobactam) Terlipressin Thiamine Tobramycin Tranexamic Acid Tramadol Thyroxine Thiopentone Warfarin Sodium 364 366 368 370 372 427 Z Zopiclone 430 S Salbutamol Sildenafil Simvastatin Sodium Bicarbonate Sodium Nitroprusside Sodium Valproate Sotalol Spironolactone Suxamethonium 374 377 379 381 384 386 389 392 394 APPENDICES (page 432 onwards) Administration Of Medicines Via Enteral Feeding Tubes Warfarin Reversal Guidelines Paracetamol Poisoning Treatment Nomogram Therapeutic Drug Level Monitoring Antibiotic Overview Opioid Dose Equivalence Acetazolamide Wellington ICU Drug Manual v2 2013 [1 vial $43.00, tablet 17 cents] ADMINISTRATION ROUTES PO, NG, IV ALTERNATIVE NAMES Diamox (Tab), Glaumox (Vial) A ICU INDICATIONS: Diuretic (particularly in the presence of metabolic alkalosis) Correction of severe metabolic alkalosis c PRESENTATION AND ADMINISTRATION PO / NG: Diamox 250mg tablets (white); for NG use, crush prior to administration e t a IV: Glaumox is supplied as a sterile powder requiring reconstitution Each vial contains an amount of acetazolamide sodium equivalent to 500 mg of acetazolamide Each 500-mg vial containing acetazolamide should be reconstituted with at least ml of sterile water for injection prior to use Reconstituted solutions retain their physical and chemical properties for 24 hours under refrigeration at 2-8°C or 12 hours at room temperature z a m i DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY: No dose adjustment is required when administered for ICU indications (beware that acetazolamide is contraindicated in the presence of metabolic acidosis) This drug is not indicated in patients on renal replacement therapy l DOSAGE IN PAEDIATRICS: The safety and effectiveness of acetazolamide in paediatric patients below the age of 12 years have not been established o DOSAGE: For diuresis, the dose is usually 250-375 mg stat If, after an initial response, the patient fails to continue to diurese, not increase the dose but allow for kidney recovery by skipping medication for a day Acetazolamide yields best diuretic results when given on alternate days, or for days alternating with a day of rest d CONTRAINDICATIONS Hypersensitivity to acetazolamide or other sulphonamides Metabolic acidosis Cirrhosis (risk of development of hepatic encephalopathy) e CLINICAL PHARMACOLOGY Acetazolamide is an enzyme inhibitor that acts on carbonic anhydrase, the enzyme that catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid Wellington ICU Drug Manual v2 2013 WARNINGS Fatalities have occurred, although rarely, due to severe reactions to acetazolamide including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anaemia, and other blood dyscrasias PRECAUTIONS General Increasing the dose does not increase the diuresis and may increase the incidence of drowsiness and/or paraesthesia Increasing the dose often results in a decrease in diuresis A Laboratory Tests No tests are required in addition to routine ICU blood tests c e Drug/Laboratory Test Interactions Acetazolamide interferes with the HPLC method of assay for theophylline Interference with the theophylline assay by acetazolamide depends on the solvent used in the extraction; acetazolamide may not interfere with other assay methods for theophylline t a z o IMPORTANT DRUG INTERACTIONS FOR THE ICU Acetazolamide modifies phenytoin metabolism with increased serum levels of phenytoin Acetazolamide increases lithium excretion and the lithium levels may be decreased Acetazolamide and sodium bicarbonate used concurrently increases the risk of renal calculus formation Acetazolamide may elevate cyclosporin levels l a m i d e ADVERSE REACTIONS Body as a Whole: Headache, malaise, fatigue, fever, pain at injection site, flushing, flaccid paralysis, anaphylaxis Digestive: Gastrointestinal disturbances such as nausea, vomiting, diarrhoea Hepato-Biliary Disorders: Abnormal liver function, cholestatic jaundice, hepatic insufficiency, fulminant hepatic necrosis Metabolic/Nutritional: Metabolic acidosis, electrolyte imbalance, including hypokalaemia, hyponatraemia, loss of appetite, taste alteration, hyper/hypoglycaemia Nervous: Drowsiness, paraesthesia (including numbness and tingling of extremities and face), depression, excitement, ataxia, confusion, convulsions, dizziness Skin: Allergic skin reactions including urticaria, photosensitivity, Stevens-Johnson syndrome Special Senses: Hearing disturbances, tinnitus, transient myopia Urogenital: Crystalluria, haematuria, glycosuria, renal failure polyuria Acetazolamide Acetylcysteine Wellington ICU Drug Manual v2 2013 [1 vial $25.53] ADMINISTRATION ROUTES: PO, NG, IV ALTERNATIVE NAMES: Acetadote, Parvolex A c ICU INDICATIONS: paracetamol overdose non-paracetamol induced fulminant hepatic failure y s t e i n e c DOSAGE IN PAEDIATRICS Paracetamol Overdose 150mg/kg over 15 minutes; 50mg/kg over the next hours, 100mg per kg over the next 16 hours Total dose 300mg/kg in 20 hours Note: In children, N-acetylcysteine should be given intravenously as a 40 mg/mL solution in 5% dextrose in water This is to prevent possible hyponatraemia l Initial Dose in Second Dose Third Dose in Total ml ml in ml ml 50 37.5 12.5 25 75 60 45.0 15.0 30 90 70 52.5 17.5 35 105 80 60.0 20.0 40 120 90 67.5 22.5 45 135 ‘x’ 0.75x 0.25x 0.5x 1.5x e.g 76kg: 0.75 multiplied by 76 = 57ml for the initial infusion dose and 19ml and 38ml for the 2nd and 3rd doses respectively Weight kg y DOSAGE: Paracetamol Overdose: 150mg/kg over 15 minutes; 50mg/kg over the next hours,100mg per kg over the next 16 hours Total dose 300mg/kg in 20 hours Initial dose: 150mg/kg in 200ml of D5W over 15 minutes Second dose: 50mg/kg in 500ml of D5W over hours Third dose: 100mg/kg in 1000ml of D5W over 16 hours t PRESENTATION AND ADMINISTRATION: PO / NG: Give IV solution orally (unlicensed section 29 use - see below) IV: Acetadote and Parvolex are supplied as sterile solutions in 10ml vials containing 20% (200 mg/ml) acetylcysteine Compatible with 5% dextrose Prepare immediately before use and discard any solution not used within 24 hours Note: Section 29 drug when administered orally (requires specific notification to Director-General of Health as unapproved route of administration) e It is not recommended for use as a preventative agent in contrast-induced nephropathy Wellington ICU Drug Manual v2 2013 W a Therapeutic warfarin doses decrease the total amount of the active form of each vitamin K dependent factor made by the liver by approximately 30-50% An anticoagulant effect generally occurs within 24 hours after drug administration, however peak anticoagulant effect may be delayed by 72-96 hours The duration of action of a single dose of warfarin is 2-5 days Warfarin may potentiate a more hypercoagulable state in the first 24-48 hours due to the more rapid depletion of the anticoagulant proteins C & S when compared to the clotting factors with longer half-lives As such, any concomitant anticoagulant therapy such as Heparin or Enoxaparin should be continued until the desired therapeutic INR is reached This initial pro-coagulant effect is increased with the use of higher loading doses Warfarin may increase the APTT test even in the absence of heparin Heparin therapy may also affect the INR r Anticoagulants have no direct effect on established thrombus but prevent further extension of the formed clot f a r i n S o d CONTRAINDICATIONS: Any condition in which the hazard of haemorrhage is greater than the potential clinical benefits of anticoagulation, such as: Pregnancy, threatened abortion, eclampsia and pre-eclampsia Haemorrhagic tendencies or blood dyscrasias Sever to moderate hepatic or renal insufficiency Recent or contemplated surgery of the CNS, eye or traumatic surgery resulting in large open surfaces Bleeding tendencies associated with active ulceration or overt bleeding of gastrointestinal/genitourinary or respiratory tracts, cerebrovascular haemorrhage, cerebral aneurysms, dissecting aorta, pericarditis and pericardial effusions, bacterial endocarditis Inadequate laboratory facilities Unsupervised senility, alcoholism, psychosis or lack of patient co-operation Spinal puncture Malignant hypertension 10 Known or suspected deficiency in protein C 11 Known hypersensitivity to warfarin i u m WARNINGS: Risk of haemorrhage in any tissue or organ related to level of intensity & duration of anticoagulant therapy Necrosis & gangrene of skin and other tissues is seen less frequently (9 Clinically significant bleeding where warfarin is a contributing factor Cease 5-10mg (iv) 25-50 IU/kg 150-300 ml Assess patient continuously until INR < & bleeding stops If FFP is unavailable, give vitamin K (5-10mg iv) & Prothrombinex (25-50 IU/kg) If Prothrombinex is unavailable, give vitamin K (5-10mg iv) & FFP (10-15 ml/kg) * Bleeding risk increases exponentially from INR to 9; INR ≥ should be monitored closely ^ High bleeding risk factors include active gastrointestinal disorders, concomitant anti-platelet therapy, major surgical procedure within preceding weeks, thrombocytopenia SEEK EXPERT HAEMATOLOGY ADVICE IF UNSURE Managing oral anticoagulation during invasive procedures according to risk of thromboembolism Therapeutic procedures before and after surgery Thromboembolism risk Low 4-5 days before Withhold warfarin 2-3 days before Night/day before If INR > 2, 1-5 mg vitamin K (iv) - Day of surgery After surgery If INR ≤ 1.5 proceed Start warfarin on same day at previous maintenance dose If INR > 1.5 defer 72 hours + after If surgery is urgent, Prothrombinex (25-50 IU/kg) + 150-300 ml FFP or FFP alone Employ thromboprophylaxis as per usual practice Recommence warfarin ASAP High Withhold warfarin Start treatment dose unfractionated heparin (iv) or low molecular weight heparin (LMWH)* (subcut) If using LMWH, last dose (max dose of enoxaparin 1mg/kg) at least 24 hours before surgery If using unfractionated heparin, discontinue 4-6 hours before surgery Start heparin or LMWH 12-24 hours postoperatively If using LMWH, give thromboprophylactic dose Fully anticoagulate patient with warfarin if no evidence of bleeding Cease heparin or LMWH 48 hours after target INR is reached If using unfractionated heparin, aim to prolong APTT 1.5x * Exercise caution in patients with impaired renal function (creatinine clearance rate < 30 ml/hour) LMWH can accumulate & contribute to bleeding NOTE: Patients with prosthetic valves & those who have had an acute thrombosis within the preceding three months should receive bridging anticoagulation peri- and postoperatively SEEK EXPERT HAEMATOLOGY ADVICE IF UNSURE APPENDIX PARACETAMOL POISONING NOMOGRAM - from Australasian Clinical Toxicology Consensus Statement Daly et al, MJA 2008; 188:296-301 Paracetamol Poisoning Treatment Nomogram 900 800 Blood Paracetamol Concentration (mg/L) Blood Paracetamol Concentration (micmol/L) 1000 700 600 500 400 300 200 100 0 10 11 12 13 14 15 Time Since Ingestion (hours) 16 17 18 19 20 21 22 23 24 APPENDIX Therapeutic Drug Level Monitoring General Principles - Only clinically relevant tests should be performed; not perform tests that cannot be interpreted or not assist patient management Random levels that not conform to the timings indicated below are not clinically useful - ‘Peak’ levels refer to the highest blood concentration of a drug after administration - ‘Trough’ levels refer to the lowest blood concentration of a drug after administration - ‘Steady-state’ refers to the situation reached when the intake of a drug equals that of its removal from the body - Blood samples should be collected only after the drug concentration has reached steady-state i.e at least half-lives at a constant dosing regimen Levels close to steady state may be reached earlier if a loading dose has been administered Drugs with long half-lives may be monitored before steady-state has been achieved to ensure patients with impaired metabolism or renal excretion are not at risk of developing toxicity at the initial dosage regimen - Drug concentrations may be requested for any of the following reasons: - Suspected toxicity - Lack of response - To assess patient compliance - To assess therapy following a change in dosage regimen - A change in clinical state of the patient - Potential drug interaction due to a change in other medications - Where manifestations of toxicity and disease are similar - To interpret a result, the details of the dosage regime (dose and duration) must be known - For patients suspected of symptoms of drug toxicity, the best time to take the blood specimen is when the symptoms are occurring - If there is a question as to whether an adequate dose of the drug is being achieved, it is usually best to obtain trough levels (rather than peak) as these are less influenced by absorption and distribution problems However, for some drugs where toxicity is a concern (such as gentamicin), peak levels may be requested - A range of drug concentrations is usually targeted rather than a specific value as the effect of a drug at a known concentration may vary greatly between individuals - Trough levels are usually obtained at the end of the dosage interval i.e immediately before the next dose is due to be given - Peak levels are usually obtained: - 30 minutes after an intravenous dose (if given by infusion, 30 minutes after the infusion has been stopped); aminoglycoside antibiotics (gentamicin, tobramycin) given by bolus should have their levels checked 30 minutes post dose to avoid the distribution phase - one hour after an intramuscular dose - one to two hours after oral dosing - slow release drugs may not produce peak levels for several hours after ingestion Drug Timing of blood sample Vacutainer tube Therapeutic Range Carbamazepine Sample immediately before next dose (trough) Red or Yellow 16-50 micmol/L Clozapine Sample immediately before next dose (trough) or at anytime if toxicity suspected Red Trough 1000 nmol/L; Toxicity >2000 nmol/L Cyclosporin Sample immediately before next dose (C0) or exactly hours post dose (C2) Purple See drug monograph for interpretation Digoxin Sample 8-24 hours post dose Red or Yellow 0.6-2.0 nmol/L Gentamicin Sample trough level 2-4 hours before next dose is due Yellow or Red (Green for paeds) See drug monograph for interpretation Lithium Sample 12 hours post dose Yellow 0.6-1.2 mmol/L Phenobarbitone Sample immediately before next dose (trough) Yellow, Red or Green 65-130 micmol/L Phenytoin Sample at least 12 hours post dose (trough) Yellow Trough 40-80 micmol/L Theophylline For i/v infusion, sample at any time Yellow, Red or Green 55-110 micmol/L Tobramycin - Trough: immediately before next dose - Peak: 30 mins post dose Red or Yellow Trough