Acetylcysteine for acetaminophen poisoning, P&T Review

·        Acetadote®, IV acetylcysteine, is non formulary; acetylcysteine for inhalation, a sterile product will be given IV and has been given IV since 1979. A 0.22 micro inline filter will be used to prepare the inhalation solution for IV use. The active ingredients, inactive ingredients, and pH are identical in the products.  A savings of $200-$700 will be realized per 20.25 hour treatment for patients weighing 40-150 kg (16.5 times less expensive). 

·        The FDA recommended dose of acetylcysteine intravenous for patients treated within 10 hours of ingestion is:

•  150 mg/kg IV over 15-60 minutes in 200 ml of D5W, followed by
• 50 mg/kg in 500 ml of D5W over 4 hours, followed by
• 100 mg/kg in 1000 ml of D5W over 16 hours.

·        The 20.25 hour IV protocol is not recommended for patients treated greater than 10 hours post ingestion, as efficacy is less than acetylcysteine administered IV for 48 hours (140 mg/kg loading dose followed by 70 mg/kg every 4 hours for 11 doses) or orally for 72 hours (140 mg/kg loading dose, followed by 70 mg/kg every 4 hours for 17 doses), see table at end of findings.

·        Among patients with fulminant hepatic failure, acetylcysteine should be given until there is recovery or death, 100 mg/kg continuous infusion every 16 hours, as mortality is reduced by 40%. (Br Med J. 1979;2:1097-100) Note: These patients were admitted 33 hours post ingestion and started the IV protocol (150 mg/kg loading dose, 50 mg/kg over 4 hours, 100 mg/kg every 16 hours) 53 hours post ingestion and were already in fulminant hepatic failure.

Prevention of Contrast Dye Nephrotoxicity, P&T Review

• Acetylcysteine, 600 mg twice a day for 2 days, starting the day before the procedure, is recommended for all patients receiving contrast dye that are at risk of developing nephrotoxicity.  Nephrotoxicity rates appear to be reduced from 17% to 8.7% in high-risk patients receiving acetylcysteine plus hydration versus hydration alone (1 ml/kg/hour for 12 hours pre procedure and 12 hours postprocedure).

• Hydration with normal saline at 1 ml/kg/hour, starting before the procedure and continuing 12 hours postprocedure is recommended for all patients receiving contrast dye. The rate of nephrotoxicity was reduced from 2% to 0.7% in a large prospective, randomized, controlled clinical trial, using normal saline versus half-normal saline at 1 ml/kg/hour for approximately 24 hours starting the morning before the procedure.  [Mueller C, Prevention of contrast media-associated nephropathy (Arch Intern Med. 2002 Feb 11;162(3):329-36)]

Autosubstitute with Loratadine/Pseudoephedrine, P&T Review

Loratadine (Claritinâ) and Claritin D 12 hour (5 mg with 120 of pseudoephedrine) are the P&T recommended formulary non-sedating antihistamines with automatic substitution for desloratadine (Clarinexâ) fexofenadine (Allegraâ 30, 60, 180 mg), Allegra Dâ (60 mg fexofenadine with 120 mg pseudoephedrine), Allegra D 24 Hourâ (180 mg fexofenadine and 240 mg pseudoephedrine), cetirizine (Zyrtecâ), and Semprex D (8 mg acrivastine with 60 mg pseudoephedrine). They will be stocked in the following dosage forms: Claritin 10 mg, Clartin D 12 hour, and as the syrup 1 mg/ml for pediatric patients.

 P&T/MEC APPROVED 11/2000, updated 3/21/07

*Note Claritin dosage in renal impairment, clcr < 30 ml/min, or hepatic failure: 2-5 years old 5 mg every other day, 6 years and older 10 mg every other day.

Recommendation:

·        Adenosine is non formulary as it does not demonstrate equivalent sensitivity to dipyridamole and is eight to ten (8-10) times much more expensive than dipyridamole ($16-32 costing per test).

Findings:

·        Indication:  adjunct to thallium-201 myocardial perfusion scintigraphy in patients unable to exercise.

·        Adenosine induces coronary vasodilation by activation of the adenosine₂ (A2) cell surface receptor.

·        Adenosine produces coronary vasodilation and dilates resistance vessel in all tissues except the kidney and liver where is produces vasoconstriction.

·        Adenosine significantly increases blood flow in normal coronary arteries with little or no increase in stenotic arteries.

·        Myocardial uptake of thallium-201 is directly proportional to coronary blood flow.

·        Adenosine produces a direct negative chronotropic, dromotropic and inotropic effect on the heart.

·        Adenosine's half-life is 10 seconds and it is cleared via cellular uptake (nucleoside transport) by RBCs and vascular endothelial cells.

·        Adenosine 140 mcg/kg/min produces maximum coronary hyperemia in approximately 95% of cases in 2-3 minutes. Blood flow returns to basal levels within one to two minutes after discontinuation of adenosine.

·        Dose: 140 mcg/kg/min for 6 minutes. Inject thallium at midpoint of adenosine infusion.

·        Contraindications:

o       2^nd or 3^rd degree heart block in patient without a functional artificial pacemaker

o       Sinus node disease (sick sinus syndrome or symptomatic bradycardiac, except in patients with a functional artifical pacemaker)

o       Known or suspected broncho constrictive or bronchospastic lung disease (asthma)

·        Warnings

o       Fatal cardia arrest, life threatening ventricular arrhythmias, and myocardial infarction have been reported coincident with adenosine infusion.  Patients with USA appear to be at greater risk.

o       Sinoatrial and atrioventricular nodal block

§        6.3% develop AV block, all have been asymptomatic, transient, and did not require intervention.

o       Hypotension

§        Use with caution in patients with autonomic dysfunction, stenotic valvular heart disease, pericarditis or pericardial effusion, stenotic carotid artery disease with cerebrovascular insufficiency, or uncorrected hypovolemia.

·        Drug interactions:

o       Vasoactive effects of adenosine are inhibited by adenosine receptor antagonists: methylxanthines (caffeine and theophylline).

o       Vasoactive effects of adenosine are potentiated by nucleoside transport inhibitors such as dipyridamole.

o       Drugs that augment or inhibit the effects of adenosine should be withheld for > 5 half-lives prior to adenosine use.

Comparison to dipyridamole

·        Adenosine produces a greater increase in heart rate, greater decrease in diastolic and systolic blood pressure

·        Adenosine incidence of adverse effects is higher, but dipyridamole has a higher incidence of late onset adverse effects.

* In patient without a functional artificial pacemaker

FDA MedWatch and Patient Safety Program

• The initial dose of Cathflo will be the priming volume of the catheter lumen up to 1 ml (1 mg/ml). If the catheter volume is greater than 1 ml normal saline will be used to fill the remainder of the catheter.  If catheter patency is not established in 60 minutes an equal volume of alteplase will be re-instilled, up to 1 ml (1mg/ml).  The same vial will be used for the initial and follow up dose.
• When orders are written for CathFlo (alteplase) may repeat x1, the pharmacist will only send one 2 mg dose (2 mg/2ml). Nursing will call pharmacy if another vial is needed. 

Priming volumes for central venous catheters

Pulse Dosing Chart: Amikacin

Traditional Dosing Calculator for Aminoglycosides

Patient Monitoring Form

Aminoglycoside and Vancomycin Dosing & Monitoring Protocol

Pulse Dosing Calculator for Aminoglycosides

Traditional Dosing Calculator for Aminoglycosides

Aminoglycoside and Vancomycin Dosing & Monitoring Protocol

• Anidulafungin (Eraxis) is formulary, P&T Review. Caspofungin (Cancidas) and Micafungin are non formulary and should not be stocked. Please recommend Eraxis when ever you get an order for Cancidas or Micafungin.
  • Fluconazole is the drug of choice for esophageal candidiasis and hematopoietic stem cell transplant (HSCT).  It is also the primary agent for febrile neutropenia 400-800 mg/day, candidemia 400 mg/day, and other candida infections 400 mg/day.
  • Voriconazole is the drug of choice for aspergillus.

   

Advantages of anidulafungin over other echinocandins.

• Anidulafungin is not a substrate, inhibitor or inducer of cytochrome P450 enzymes. It has only one known drug interaction (cyclosporine), but anidulafugin’s does not require a dosage adjustment
  • Medications studied include rifampin, cyclosporine, tacrolimus, voriconazole, and amphotericin B
• Anidulafungin has the longest half-life (26 hours) and the lowest protein binding (84%) of the echinocandins.
• Anidulafungin is chemically degraded in the body and is not metabolized by the cytochrome P450 system
• Anidulafungin does not require dosage adjustment for liver or renal dysfunction
• Anidulafungin is less expensive than other echinocandins
• Anidulafungin provides higher free levels than caspofungin and micafungin
• Anidulafungin’s adverse effect profile appears to be better than other echinocandins
• Antifungal spectrums of echinocandins are equivalent.
  • Anidulafungin has a broad spectrum activity against Candida (including those strains that are resistant to polyenes and azoles), non-albicans strains and Aspergillus species. Potential synergy with azoles against Aspergillus has been demonstrated in vitro. It is inactive against Cryptococcus neoformans, Trichosporon spp., Zygomycetes and Fusarium. All echinocandins are less active against C. parapsilosis
• Anidulafugin is the only echinocandin that has been studied in a randomized control trial versus fluconazole in candidemia and other invasive candida infections (phase three clinical trial, not published)

* Patients with at least 1 dose of study drug and a positive culture for Candida species for a normally sterile site, clinical cure or improvement and documented or presumed microbiological eradication

** Patients with C. krusei (fluconazole not active), candida endocarditis, osteomyelistis, and meningitis were excluded from the study

Dolasetron (Anzemet) was removed from formulary as it may cause ECG (PR and QTc prolongation, QRS widening), which usually reverses in 6 hours but may last up to 24 hours

Aprotinin, P&T Review, is recommended for high-risk patients: repeat CABG, valve replacement and repairs, bleeding time longer than 10 minutes, history of bleeding diathesis, preoperative coagulopathy, and patients receiving aspirin, Plavix, or Aggrenox within 5 days of surgery.

Half-dose aprotinin is not recommended, as it is not more cost effective than full dose aprotinin

Aminocaproic acid is recommended as an alternative to aprotinin for low risk cardiac surgery patients.

·        Oral Aprepitant (Emend^TM) is on formulary for chemotherapy induced nausea and vomiting.

·        Oral Aprepitant, in combination with a 5HT3 antagonist and dexamethasone, is FDA approved for prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (including high dose cisplatin).

·        The FDA recommended dosage of aprepitant, 1 hour before chemotherapy, is 125mg orally on day 1 and 80mg orally on days 2 -3, along with a 5HT3 receptor antagonist on day 1, and dexamethasone on days 1-4. 

·        Granisetron 2 mg PO and dexamethasone PO are recommended to be given in combination Aprepitant as efficacy is unchanged and cost is reduced by using the oral route. The American Society of Clinical Oncology recommends the oral route.  Orders will be entered for the oral route unless the patient is unable to use oral route.

Aprepitant for Prophylaxis for Postoperative Nausea & Vomiting, P&T Review

·      Aprepitant (Emend™)  is not formulary for prevention of postoperative nausea and vomiting (PONV), MEC APPROVED. The multiple center study conducted in the U.S. failed to demonstrate a statistically significant difference between aprepitant 40 mg oral and a single dose of ondansetron 4 mg injection.

o       Zofran administration was not timed appropriately in the studies

o       Agents from multiple classes may be combined for patients at high risk of PONV (dexamethasone, 5HT3 receptor antagonists, droperidol, prochlorperazine) to reduce the risk of PONV at a lower cost with a high efficacy rate.

o       Coadministration of aprepitant with warfarin may significantly decrease INR for those patients on chronic warfarin therapy.  Monitor closely in the two week period (particularly at 7-10 days) following both the 3 day chemotherapy regimen and the one time 40 mg dose of aprepitant.

o       Patients using oral contraceptives require an alternative method for one month following aprepitant.

o       The Antiemetic Prophylaxis For Patients At Risk For PONV card will be made available to the anesthesia groups to help promote a more systematic approach.

*Zofran is expected to become available in the generic form on 12/06.

• The dosing and monitoring protocol on the physician preprinted order form will be used when argatroban is ordered for treatment of heparin-induced thrombocytopenia (HIT)
• The preprinted physician order form will be used for all orders.
• Pharmacy will send the infusion rates charts and the rate change dosing chart when dispensing argatroban, see links below.

Argatroban Non Cath Lab 250 mg / 250 ml (normal liver function),

Argatroban Non Cath Lab 250 mg / 500 ml for Patients With Liver Dysfunction

Rate Change Based on aPTT Dosing Chart for Nursing

Hepatic Disease Score Calculator

Argatroban Monitoring Algorithm if Concurrent Warfarin administered

·        Fondaparinux (Arixtra®), P&T Review, is formulary restricted to hematologists for patients who have or have had heparin induced thrombocytopenia or who are allergic to LMWH. Pharmacy will automatically adjust the dose of fondaparinux, when ordered for DVT/PE treatment, based on the patient’s renal function and lean body weight (see the links below for details).

o       Pharmacy will determine the patient's creatinine clearance and lean body weight before dispensing fondaparinux.

o       Patients will not receive fondaparinux unless a recent serum creatinine has been determined and the calculated creatinine clearance is > 30 ml/min.

o       Fondaparinux prophylaxis should not be given to patients weighing < 50 kg following orthopedic surgery.

o       Fondaparinux is contraindicated in patients with bacterial endocarditis

o       Patients receiving fondaparinux will have a serum creatinine and BUN determined every other day during therapy.

o       Fondaparinux Anti Xa levels will be drawn 12 hours after the third dose.

Arixtra Dosing Protocol

Therapeutic Dosing Based on Dosing Weight and Renal Function, 

Therapeutic Dosing Based on Levels,

Prophylaxis Dosing Chart Based on Dosing Weight and Renal Function,

Prophylaxis Dosing Chart Base on Levels

Arixtra Dosing Calculator and Data Fitting For Mid Point Levels

Fondaparinux Pharmacokinetic Monitoring Form

·     Arsenic Trioxide, P&T Review, is formulary for induction of remission and consolidation in patients with acute promyelocytic leukemia (APL) who are refractory or have relapsed from retinoid and anthracycline chemotherapy.  APL must be characterized by the presence of the t (15; 17) translocation or PML/RAR-alpha gene expression. Use of this agent will be restricted to certified oncologists.

·       All patients will have an ECG to document the QT interval and current medications will be screened by the pharmacists for propensity to cause QT interval prolongation. http://www.torsades.org

·       Arsenic trioxide will only be administered in the oncology unit or in the outpatient infusion center.

·       A list of medications with risk of Torsade de Pointes will be provided to the patient by nursing staff.

·       ECG will be repeated weekly during therapy.

·       If administered in the outpatient infusion center, documentation of weekly ECG will be required by the infusion center.

·       If absolute QT is >500 msec, risk factors will immediately be corrected (electrolytes, concomitant drugs) and will reassess risk/benefit of continuing versus suspending arsenic trioxide.

·       If syncope, rapid or irregular heartbeat occur: hospitalize and monitor the patient continuously, and hold TRISENOX® until QTc is <460 msec and symptoms resolve.

·       5-HT₃ receptor antagonists will be used with caution as some cause QT interval prolongation (Anzemet should not be used and is non formulary).

·       Electrolytes will be monitored and kept above the following values:

·       Potassium  4 meq/l

·       Magnesium 1.8 mg/dl

·       The patient will be monitored for APL differentiation syndrome:

·       Fever, fluid retention, musculoskeletal pain, pulmonary infiltrates and pleural or pericardial effusions, with or without leukocytosis, and dyspnea.

·       Patient weight will be recorded daily and monitored for >2 lbs. gain in 24 hours by nursing staff.

·       The patient will be taught signs and symptoms of APL differentiation syndrome by nursing staff and will be asked to report any signs and symptoms.

·       At the first sign of APL differentiation syndrome, dexamethasone 10 mg BID will be administered and continued for at least 3 days until signs and symptoms have abated.

Azithromycin IV is recommended as the preferred IV azalide/macrolide, and is recommended for automatic substitution for erythromycin IV except for the following: patients less than 16 years old, pregnancy, and L&D uses.

Sensitivity of streptococcus pneumoniae is similar for macrolides and azalides (azithromycin, clarithromycin, and erythromycin) for penicillin sensitive, intermediate, and resistant strains with 90%, 70%, and 30% being sensitive, respectively.  Cross-resistance occurs to the class.