℞ FYDI ℞

……………For Your Drug Information ………….

OSF Saint Francis Medical Center January 2001 Peoria, IL

Pharmacy and Therapeutics Committee Activities (Sept-January)

Formulary Additions:

  1. Anti-thymocyte globulin(rabbit) Thymoglobulin® for the treatment of acute renal transplant rejection. See July-August 2000 FYDI newsletter for review of this drug.
  2. Bisoprolol(Zebeta®)- a long acting, cardioselective beta adrenergic blocking agent without membrane stabilizing or intrinsic sympathomimetic activities. P&T committee has requested that the Medical Staff write for this medication using both the generic and brand name due to possible confusion with Diabeta®.
  3. Tolterodine (Detrol®) – is a nonsubtype selective antimuscarinic agent used for the treatment of

    4. patients with overacive bladder with symptoms of urinary frequency, urgency, or urge incontinence. It acts by mucarinic receptor blockade in the bladder wall and detrusor muscle.

  4. Piperacillin/tazobactam(Zosyn®) – considering switching from ticarcillin/clavulanate (Timentin®) due to better antipseudomonal coverage seen with Zosyn®. Watch for switch in February or March.
  5. Miralax®- this is a polyethylene glycol 3350 powder recently added to formulary to replace Colyte® 1350 ml which is no longer commercially available.

  6. Tizanidine (Zanaflex®)- a skeletal muscle relaxant used for treatment of muscle spasms.

Formulary Deletions and Drug Recalls:
  1. Tirofiban (Aggrastat) – results of the recent TARGET study showed abciximab(Reopro®) to be a a superior 2b3a glycoprotein inhibitor when compared to tirofiban. Prompted the decision to remove tirofiban from formulary.
  2. Phenypropanolamine containing products were all removed from the market by the FDA due to continued reports that the drug is associated with increased risk of hemorrhagic stroke.
  3. Alprazolam (Xanax®) has been deleted and can be autosubstituted to lorazepam (Ativan®). Dose conversion would be 1 mg lorazepam is equivalent to 0.5 mg of alprazolam. Lorazepam is available in unit dose, less costly, and has a better interaction profile than alprazolam.
  4. Alosetron (Lotronex®) has been withdrawn from the market due to reports of serious adverse effects in postmarketing surveillence (ischemic colitis, severe constipation, and bowel obstruction). The drug was never on formulary at OSF Saint Francis Medical Center.

New FDA marketing approvals:

  1. Oxcarbazepine(Trileptal®) – an oral anticonvulsant structurally related to carbamazepine. Approved for use in adults as adjunctive treatment and monotherapy for partial seizures and as adjunctive therapy in children 4 to 16 years old. Give as twice daily dosing, 600 mg BID. Trileptal® has a 25-30% chance of cross sensitivity in those patients with prior allergy history to carbamazepine. Trileptal® is associated with Cytochrome P450 interactions and can affect the metabolism of other anticonvulsants.
  2. Cevimeline(Evoxac®) – an oral muscarinic agent for dry mouth in Sjogren’s Syndrome. Evoxac® is a cholinergic agent that acts on the exocrine glands, such as the sweat and salivary glands. The recommended dosing for Evoxac® is 30 mg TID.
  3. Zonisamide(Zonegran®) - an oral broad-spectrum anticonvulsant useful for a variety of seizures ( partial and generalized). FDA approved for use as adjunctive therapy for partial seizures in adults with epilepsy. Zonegran® is a sulfonamide and is contraindicated in all patients with hypersensitivity reactions to sulfa drugs. Doses range from 100-400mg daily.
  4. Gemtuzumab ozogamicin(Mylotarg®) – a recombinant humanized anti-CD33 monoclonal antibody conjugated to calicheamicin (a cytotoxic agent). Indicated for patients with CD33 positive acute myeloid leukemia(AML) in first relapse. Patients should be ³ 60 years of age and should not be considered as candidates for cytotoxic chemotherapy. Mylotarg® is extremely light sensitive and must be protected from light during preparation and administration. Mylotarg® should be diluted with normal saline prior to administration and has been associated with severe infusion related reactions. Patients should be pre-medicated with diphenhydramine and acetaminophen. Acetaminophen should be continued post-infusion to decrease severity of infusion-related reactions.
  5. Insulin aspart(Novolog®) – SC insulin for treatment of adult patients with diabetes mellitus. Novolog® has a rapid onset of action and a shorter duration of action than regular insulin. Novolog® should be used in an individualized regimen together with an intermediate or long acting insulin. Novolog® should be administered SC 5-10 minutes prior to a meal. ?? advantage over Insulin Lispro.
  6. Triptorelin(Telstar®) Depot – a synthetic agonist analog of luteinizing hormone releasing hormone(LHRH) for use as palliative treatment of advanced prostate cancer. Telstar® is an alternative for patients where orchiectomy or estrogen administration is not indicated or acceptable. Trelstar® is given as 3.75mg dose IM once monthly.
  7. Tinzaparin(Innohep®) – a SC low-molecular weight heparin for use in DVT with or without PE when administered in conjunction with warfarin. Innohep® is dosed at 175 IU/kg once daily for ³ to 6 days and until the patients warfarin therapy produces INRs ³ 2 for 2 consecutive days. Warfarin and Innohep® therapy generally require a 3 day overlap.
  8. Argatroban(Acova®) – a synthetic, selective, direct thrombin inhibitor. It is indicated for anticoagulation in patients with heparin-induced thrombocytopenia. Therapy is initiated at 2 mcg/kg/min as a continuous infusion and is adjusted based on aPTT. Desired goals are aPTT 1.5-3 times the baseline (not to exceed 100 seconds). It is similar to lepirudin (Refludan) except Argatroban requires no renal dosage adjustments and has a shorter elimination t1/2 (< 30min).
  9. Unoprostone isopropyl(Rescula®) 0.15% opth drops – an ocular hypotensive agent used for treating open-angle glaucoma. Similar to latanoprost (XalatanÒ )
  10. Eflornithine(Vaniqa®) cream – for the topical reduction of unwanted facial hair.
  11. Levofloxacin opthalmic(Quixin®) – a opthalmic fluoroquinolone antibiotic for use in the treatment of bacterial conjunctivitis.
  12. Cetorelix(Cetrotide®) – a subcutaneously administered LHRH antagonist for fertility.
  13. Docosanol 10% (Abreva®) cream– a broad-spectrum antiviral agent for topical use. Indicated for recurrent oral-facial herpes simplex.
  14. Lopinavir 133.3mg/Ritonavir 33.3mg (Kaletra®) – a coformulation of lopinavir, protease inhibitor for the treatment of HIV-1 infections and ritonavir, another protease inhibitor. Ritonavir in this formulation is used solely to inhibit the CYP3A mediated metabolism of lopinavir and not for its antiretroviral effects. This allows for better bioavailability of lopinavir. Approved for use in adults and pediatric patients 6 months or older.
  15. Mitepristone(Mifeprex®) – a progesterone receptor antagonist for the medical termination of intrauterine early pregnancy, defined as less than or equal to 49 days, counting from the beginning of the last menstrual period.
  16. Ropivacaine(Narapin®) – for the production of local or regional anesthesia for surgery and for acute pain management.
  17. Tazarotene(Tazorac®) – for the treatment of plaque psoriasis.
  18. Arsenic trioxide(Trisenox®) – an antineoplastic arsenical compound used for induction of remission and consolidation in patients with acute promyelocytic leukemias that are refractory to or relapsed from conventional therapy.
  19. Sodium phosphate (monobasic and dibasic salt)(Visicol®) – Cleansing prep prior to colonoscopy for adults 18 years or older.
  20. Anastrazole(Arimidex®) – First line treatment of postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer..
  21. Botulinium toxin type B(Myobloc®) – for the treatment of cervical dystonia, to reduce the severity of abnormal head position and neck pain.
  22. Bivalirudin(Angiomax®) – another direct thrombin inhibitor and synthetic analog of recombinant hirudin. It is FDA approved as an anticoagulant for patients with unstable angina undergoing PTCA. It is intended for use with aspirin.
  23. Nateglinide(Starlix®) – used as monotherapy or as an adjunct to diet and exercise to improve glycemic control in patients with Type II diabetes. Can be used in combination with metformin.
  24. Letrazole(Femara®) – treatment of postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer.

 

Drug In Review

Drug information notes:
  1. A pediatric patient inadvertently received an expired dose of tetanus toxoid in the emergency department. Wyeth-Ayerst Pharmaceuticals stated that an arthus-type reaction can occur from administration of too much toxoid. We suggested that antibody titer levels be drawn no sooner than 4 weeks post-vaccination (with expired product), than reassess need for re-vaccination at that time.
  2. Recently, pharmacists have been seeing orders for larger doses of Vitamin E and Vitamin C on many neurology inpatients. A search of current drug information literature suggests that these vitamins may be useful as free radical scavengers and anti-oxidants for prevention of cognitive dysfunction, dementia, resuscitating the injured CNS in various CNS traumas (e.g. spinal cord injury, subarachnoid hemorrhage, cerebral edema, etc).

Drug information Q and A:
  1. Can dexmedetomidine(Precedex®) be used for a period greater than 24 hours?

    2. Precedex® is currently only approved by the FDA for use in initially intubated and mechanically ventilated patients. The use of the drug is limited to no longer than 24 hours. P&T committee is requiring the use of a 24 hour automatic stop order (ASO) for Precedex®, with the inability to reorder the drug for 48 hours. A physician would have to call P&T chairman (Dr. Getz) for approval of use beyond the initial 24 hour period.

    The FDA has required Abbott Laboratories, the maker of Precedex® to conduct safety studies using the drug for greater than a 24 hour period. Studies are currently ongoing.

    Some concerns associated with extended duration of use include:

    - Potential for clonidine-like withdrawal syndrome (nervousness, agitation, hypertensive crisis).

    - Dog studies showed that when Precedex® was given by continuous subcutaneous infusion for

    7 days, the dogs developed adrenal insufficiency (40 % reduction in ACTH-stimulated cortisol

    release).

  2. What is the incidence of hepatotoxicity associated with Timentin®?

    3. Transient increase in serum levels of AST(SGOT), ALT(SGPT), and alkaline phosphatase have been reported with Timentin®. Increased serum levels of LDH and bilirubin may also occur. Transient hepatitis and cholestatic jaundice have occurred rarely during therapy with Timentin® (AHFS Drug Information 1999). No case reports of clinical hepatotoxicity have been reported to date. (Drugdex 2000)

    Adverse reactions more commonly associated with Timentin® include hypersensitivity reactions(0.7-10 % incidence), hypokalemia(due to sodium content), and gastrointestinal effects(nausea, diarrhea, and antibiotic associated pseudomembraneous colitis). Timentin® has also been associated with bleeding abnormalities(affects platelet function), and is more common in patients with renal impairment. (Facts and Comparisons 2000)

  3. What are the CDC recommendations for adult patients who have had their Hepatitis B vaccination series interrupted?

    4. The Hepatitis B vaccine is generally given in a three-dose schedule. In adults, the series is usually given at 0, 1 and 6 – 12month after initial dose. If the vaccination series is interrupted after the first dose, the second dose should be administered as soon as possible. If only the third dose is delayed, then administer when convenient but no sooner than 2 months from the previous dose. The first and second doses are responsible for the immediate and active immunity. The last dose acts as a booster dose and is responsible for long-term immunity. (CDC recommendations – MMWR web page.copy in DI file).

  4. Can bumetanide (BumexÒ ) be administered as a continuous infusion? How?

    5. Bumetanide (Bumex®) may be given by continuous infusion, with starting doses based on the patient’s current daily usage of the medication(ie. total dose/day = 6 mg IVP, or P.O, administer 0.25 mg/hr over 24 hours). Bumex® can be mixed in D5W, 0.9% NaCl, or Lactated Ringers solution and is stable for 24 hours.

    Patients should be monitored for musculoskeletal symptoms. This reaction is dose related, seen more commonly at rates of approximately 2 mg/hour, not associated with any specific risk factors, and is reversible with discontinuation of the infusion. Transient or permanent ototoxicity may occur if doses exceeding 10mg/day are given. (Drugdex 2000)

  5. Is diphenhydramine(BenadrylÒ ) contraindicated for asthmatic patients since it is has anticholinergic properties?

    6. In most reference, Benadryl® (diphenhydramine) has contraindications about its use in asthmatic patients. This is mainly due to its anti-cholinergic effects that can cause thickening of bronchial secretions and may induce bronchospasms in these patients. Some patients, however, have an allergic component to their disease and the allergic reaction can precipitate an asthmatic attack. Benadryl has been reported in some literature as useful in these cases. However, since newer antihistamines with no or minimal anticholinergic effects are available [ i.e. loratidine (ClaritinÒ ) or fexofenadine (AllegraÒ )] , they should be used instead.

  6. How do we administer influenza vaccine to patients with latex allergies?

For patients with latex allergies requiring the influenza vaccine (Fluzone®), the following has been recommended:

The vials do contain latex in their rubber stoppers and the pre-filled syringes have latex-free plungers but the needle covers contain latex.

(from : Aventis/Pasteur)

Investigational Drug Services Updates:

The following studies have been closed: The following studies are still open/opening:

    1. Bayer IVIG Study 1. A-Z Study
    2. CATO Stroke Study(Phase I) 2. Baxter r-AHF-PFM Study
    3. Porfiromycin Study 3. Chiron Sepsis Study
    4. Pfizer Stroke Study 4. Covance – Diabetic Foot Study
    1. `. Ritz-4(tezosentan) Study
    2. 7. Dr. Wang’s heparin/reopro Stroke Study

      3. 8. Voriconazole Study(compassionate use)

    3. 9. Cubist – Pneumonia Study