℞ FYDI ℞

……………For Your Drug Information ………….

OSF Saint Francis Medical Center Peoria, IL

September – October 2002

New FDA marketing approvals:

1). Oxaliplatin (Eloxatin®): Chemotherapeutic agent developed by Sanofi-Synthelabo for the use in combination with infusional 5-fluorouracil and leucovorin for the treatment of colorectal cancer that has recurred or has worsened following initial therapy with irinotecan, bolus 5-fluorouracil, and leucovorin. Doses used were 20 – 25 mg/square meter. The package insert will contain a black box warning about possible anaphylactic-type reactions. Eloxatin® can also cause neurotoxicity in either an acute or cumulative pattern of side effects. The toxic effect on nerve endings often improves after the drug treatment is complete.

2). Escitalopram (Lexpro®): A second generation version of citalopram (Celexa®) used for the treatment of depression. The drug is marketed by Forest Laboratories and will be dosed as 10-20 mg daily.

3). Influenza vaccine, preservative-free (Fluzone®): The first preservative-free (thimerosal/mercury) influenza vaccine, developed by Aventis SA to boost public confidence in the pediatric immunization and approved for infants ages 6 to 35 months. This vaccine will be available as pre-filled syringes in early to mid-November but only to a limited quantity for the 2002-2003 season due to the current manufacturing schedule.

4). Subutex® and Suboxone® for Opiate Dependence. Both drugs contain the active ingredient, buprenorphine hydrochloride. Subutex® which is indicated primarily for initial drug abuse treatment, contains buprenorphine alone. Suboxone® contains a combination of buprenorphine and naloxone and is used for maintenance treatment in opiate addicts. Both drugs are listed as Schedule III drugs since buprenorphine is considered to have a decreased potential for psychological and physical dependence compared to morphine, fentanyl, or methadone. Unlike methadone, Subutex® and Suboxone® do not have to be dispensed in clinics that specialize in addiction treatment. Instead, specially trained physicians may prescribe either of these drugs in doctors’ offices. Both drugs are available in 2 and 8 mg tablets and are given sublingually. The most common side effects are flu-like symptoms, headaches, sweating, sleeping difficulties, nausea, mood swings, and respiratory depression.

Drug Information Notes:

1). How high of a loading dose of is clopidogrel (Plavixâ ) is needed?

Evidence from the CLASSICS trial demonstrated clopidogrel was effective in the prevention of post-stent thrombosis. The dosing regimens compared were 300mg clopidogrel pre- and 150mg post-PTCA with stent placement, followed by 75mg once daily effective for prevention of stent-associated thrombosis, clopidogrel 75mg once daily, and alternative regimens including loading and non-loading doses of ticlopidine. All treatment arms received aspirin. In this trial, the clopidogrel loading dose regimen was associated with a less than 1% incidence of post-stent thrombosis.1

More recent non-randomized pharmacodynamic studies suggest higher loading doses (450mg - 600mg) of clopidogrel lead to more complete and rapid inhibition of the adenosine diphosphate receptor. Kastrati, et al2, compared a loading dose of 600mg, 2-4 hours prior to intervention, 150mg once daily until discharge, and 75mg once daily for 4 weeks post-intervention in addition to concomitant aspirin to standard ticlopidine dosing. Ticlopidine was the gold standard at the initiation of this study. The use of abciximab was at the discression of the investigators. The clopidogrel regimen was found more effective with no notable differences in bleeding between the groups. Seyfarth, et al3 evaluated the pharmocodynamic effects of the 450mg loading dose. The group found 450mg doses shorten the period until the maximum effect of the adenosine diphosphate receptor antagonism is achieved by 2 hours. Further studies are underway to evaluate the clinical significance of these doses in a randomized fashion and in conjunction with glycoprotein IIbIIIa inhibitors and/or thrombolytics.

  1. Circulation 2000;102:624.
  2. Kastrati PJ, et al. Clopidogrel therapy in patients undergoing coronary stenting: value of a high-dose regimen. Cath Cardiovasc Interv. 2002;55(4):436-41.
  3. Seyfarth HJ. Effect of 300 - and 450mg clopidogrel loading doses on membrane and soluable P-selectin in patients undergoing coronary stent implantation. American Heart Journal 2002;143(1):118-23.

 

2). How can we prepare "Mucomyst and cola" for prevention of radiographic-contrast-agent-induced reduction in renal function?

Mucomyst (20% acetylcysteine) can be diluted to yield the usual final concentration of 5% acetylcysteine1. Cola or other soft drinks can be used to increase the palatability of PO administration. Sodium chloride for injection or inhalation, or sterile water for injection or inhalation can be used as a diluent for NG use. Also, the undiluted 10% Mucomyst solution can be used per manufacturer. The diluted product should be freshly prepared and used within one hour of preparation. The unused portion of the product in the vial expires in 96 hours if it is stored in refrigerator. Mucomyst 600mg PO bid for 2 days, on the day before and on the day of using aiopromide, a radiographic contrast agent, was shown to be effective in prevention of reduction in renal function2.

1. Drugdex in Thomson Micromedex. vol 114. exp Jan 31, 2003. Drug evaluation topic: Acetylcysteine.

2. Tepel M, Giet M, Scharzfeld C, et.al. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med 2000;343:180-3.

3). What can we use for oral Vancomycin solution?

The manufacturer (Eli Lilly) has discontinued making oral Vancocin solution. Since oral capsules cannot be opened up and dissolved easily for compounding, we use Vancomycin powder for injection (Abbott) to compound the solution for PO and NG administration per package insert and Abbott medical information. The adult total daily dose for C. diff colitis is 500 mg - 2 gm given in 3-4 doses for 7-10 days or pediatric dose of 40mg/kg given in 3-4 doses. Doses can be diluted in 30 ml of water and common flavoring syrup for PO use, which will yield the common concentration of approximately 16mg/ml (500mg/30ml).

 

 

4). How can we give Temodar (temozolomide) per G-tube?

Temodar capsules are indicated for the treatment of refractory anaplastic astrocytoma. The product information sheet by Schering states that the capsules should not be opened because of the carcinogenicity. Also, there is no data available on the pharmacokinetics of Temodar in any food or liquid. However, the data on file at Schering are suggestive of stability up to 120 minutes when mixed with apple juice or applesauce. Therefore, the G-tube doses may be prepared by mixing the contents of Temodar capsules with apple juice in chemo hood on daily on-call basis.

 

Investigational Drug Services Updates:

The following studies have been closed: The following studies are active:

DCVax – Prostate Cancer Study Apollo Study

Baxter r-AHF-PFM Study

CancerVax Melanoma Study

Cardiology – Fenoldopam Study

Covance (diabetic foot) Study

DTI – 0009 Study

Exclaim Study

ISO Study (UICOMP opoid study)

Synergy Study

Dr. Wang’s heparin/reopro Stroke Study

 

(Major contributions by: Ann Corkery, Sandy Salverson, Kim Scully)