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FYDI ℞……………For Your Drug Information ………….
OSF Saint Francis Medical Center Peoria, IL
July –September (2001)
New FDA marketing approvals:
approved as an alternative therapy to amphotericin B against aspergillosis. Current drugs available for aspergillosis: Amphotericin B; itraconazole … see drug in review.
or prevent hemorrhage, and to reduce the need for clotting factor replacement therapy during and after dental extractions.
group. Used for maintenance treatment of asthma, for prevention of exercise-induced bronchospasm, and can be used in conjunction with other therapies for asthma.
The product is an oral formulation which comes in 50mg and 100 mg capsules. Gleevec blocks the rapid growth of white blood cells via inhibition of the translocation-created enzyme. Most common side-effects include: nausea, vomiting, diarrhea, edema (fluid retention), muscle cramps, skin rash, heartburn and headache. Severe fluid retention has occurred in up to 2% of patients treated.
( >10days).
The following items are NEW combinations of previously existing drugs:
Duoneb® - contains albuterol and ipratropium in solution for nebulization.
Glucovance® - contains metformin and glyburide
Rebetron® - kit contains injectable interferon alfa-2b(Intron A®) and oral ribaviran(Rebetol®)
Drug Safety issues:
Arsenic Trioxide (Trisenox)
– Non-formulary item: Added monitoring ECG and electrolyte monitoring recommendations in their labeling to specifically address the prolonged QT interval associated with this drug.Cerivastatin (Baycol) - Non-formulary item: Withdrawn from market by manufacturer due to several reports of serious (sometimes fatal) rhabdomyolysis especially among the older patients receiving high doses and those taking it in combination with gemfibrizol ( LOPID). (August – MD consult; FDA notices)
Itraconazole (Sporonox) – OSF Formulary item : Black box warning added : Avoid use in patients with CHF or other forms of cardiac dysfunction. This is in response to 94 cases of CHF patients taking itraconazole out of which 54 cases were attributed to cause or contribute CHF. The drug can have negative inotropic effects per recent studies . (May – MD consult)
Itraconazole (Sporonox) or Terbinafine (Lamisil) – The FDA has issued a public health advisory concerning reports of several cases of liver failure among patients taking Sporonox or Lamisil for fungal nail infections. Janssen Pharmaceutics recommends taking nail specimens to confirm the diagnosis of fungal infection prior to start of therapy. (May – MD consult)
Nevirapine (Virammune) – OSF formulary item: Severe hepatotoxicity reported (~ 14 people) with its use among health care workers for post-HIV exposure prophylaxis. Subsequent review found ~18 more reported ADE’s which were considered serious.
Drugs In Review:
Caspofungin Acetate(Cancidas®)
by Ann Corkery, Pharm.D.
A member of a distinct class of antifungal agents called the echinocandins. This group of antifungals inhibits the synthesis of beta (1,3)-D-glucan, an integral part of the fungal cell wall. The drug is indicated for the treatment of invasive aspergillosis in patients who are refractory to or intolerant to other antifungal therapies.
Caspofungin has complicated pharmacokinetics with a terminal half-life of 40-50 hours. Distribution, not excretion or biotransformation is the primary mechanism influencing plasma clearance. The drug is highly protein bound to albumin(~ 97%). Caspofungin is metabolized in the liver and doses may need to be adjusted in patients with moderate hepatic insufficiency(daily doses of 35 mg). Renal clearance of parent drug is low(~1.4%). There are no dose adjustments for patients with mild to severe renal impairment. The drug is not dialyzable, dose supplementation is not necessary following hemodialysis.
For treatment of invasive aspergillosis a 70mg I.V. loading dose is administered on Day 1, subsequent doses are 50 mg I.V. daily. Duration of therapy depends on the severity of the patient’s disease. The drug is administered by slow infusion over 1 hour. Caspofungin is NOT compatible with dextrose compatible solutions.
Drug interactions with caspofungin include the following:
Tacrolimus levels may be reduced when co-administered with caspofungin, monitor tacrolimus levels.
Caspofungin levels may be increased when given concomittantly with cyclosporine.
Monitor for signs of caspofungin toxicities. May see transient elevations of ALT and AST.
The manufacturer does not recommend coadministration of these two drugs unless benefits outweigh the risk.
Drugs that induce liver metabolism or are mixed inducers/inhibitors such as efavirenz, nelfinavir, nevirapine, phenytoin, rifampin, dexamethasone, or carbamazepine may decrease caspofungin levels. If patient is NOT responding clinically to 50 mg daily dose, may want to consider an increase to 70 mg maintenance dose.
Safety and effectiveness have not been studied in the pediatric patient population.
Adverse reactions to caspofungin include hypersensitivity, rash, facial swelling, infusion related complications (phlebitis), headache, asthenia/fatigue, fever, nausea and vomiting. Decreases in hematocrit, hemoglobin, neutrophils, and platelets have also been reported. The drug can cause transient elevations in liver function tests, and decreases in serum potassium.
Caspofungin is currently non-formulary at OSF Saint Francis Medical Center.
Facts and Comparisons, Cancidas® drug monograph.
Micromedex 2001, Cancidas® drug monograph.
Product information, Cancidas® Merck & Co, Inc.
Nesiritide (NatrecorÒ )
Presented by Neil Heineke
Butler University Pharm D. Candidate
Natrecorâ (nesiritide) is a member of a new drug class, which are synthetic versions of human hormones. The drug class, human B-type natriuretic peptides, binds to receptors in smooth muscle and endothelial cells, which causes an increase of cyclic GMP and smooth muscle relaxation. The cyclic GMP then serves as a second messenger to dilate veins and arteries. In human studies, nesiritide has been shown to produce dose-dependent reductions in capillary wedge pressure and systemic arterial pressure in patients with heart failure. Natrecor is indicated for intravenous treatment of patients with acutely decompensated congestive heart failure (ADCHF) who have dyspnea at rest or with minimal activity.
Natrecor has a mean terminal half-life of 18 minutes and exhibits biphasic disposition from plasma. In clinical trials, Natrecor’s clearance was found to be proportional to body weight and carried out via three independent mechanisms: Binding to cell surface clearance receptors with subsequent cellular internalization and lysosomal proteolysis, proteolytic cleavage, and renal filtration.
It is recommended that Natrecor be dosed at 2ug/kg IV bolus followed by intravenous infusion of 0.01 ug/kg/min. There is limited data on administration of Natrecor for longer than 48 hours. Natrecor is NOT compatible with injectable heparin, insulin, ethacrynate sodium, bumetamide, enalaprilat, hydralazine, and furosemide.
At this time, there are no trials that examined specific potential drug interactions with Natrecor. However, in clinical trials conducted thus far, an increase in symptomatic hypotension was noted in patients who were concomitantly taking oral ACE inhibitors.
The safety and effectiveness of Natrecor has not been established in the pediatric population. In addition, it is unknown whether the drug is excreted in human milk or if it is harmful to a fetus.
Adverse reactions to Natrecor include hypotension, ventricular tachycardia, ventricular extrasystoles, angina pectoris, bradycardia, headache, abdominal pain, back pain, insomnia, dizziness, anxiety, nausea, and vomiting. In clinical trials, it was noted that serum creatinine levels were elevated above baseline more frequently in Natrecor-receiving patients than standard therapy patients.
Natrecor is supplied as a 1.5 mg vial. It is prepared by adding 5 mL of diluent from a 250 mL pre-filled bag (5% Dextrose Inj (D5W), 0.9% Sodium Chloride Inj, 5% Dextrose and 0.45% Sodium Chloride Inj, or 5% Dextrose and 0.2% Sodium Chloride Inj). This then gives a concentration of Natrecor of 6 ug/mL. The bag is stable for 24 hours.
Natrecor is non-formulary at OSF Saint Francis Medical Center.
Micromedix 2001, Natrecorâ drug monograph.
Product information, Natrecorâ Scios Inc.
Drug information notes:
Ferrlecit – sodium ferric gluconate complex – indicated for the treatment of iron deficiency anemia in patients undergoing chronic hemodialysis. The labeling change now allows undiluted product to be given without a test dose at a rate of 12.5mg/min. This is based on 1,097 patients tested in a post-marketing study. (see drug information file on Ferrlecit for the press release information).
32.0mcg/ml /hr to 2.92mcg/ml/hr. It may be prudent to minimize the administration time overlap between these 2 drugs. (Clinical Pharmacology & Therapeutics Dec 2000)
Investigational Drug Services Updates:
The following studies have been closed: The following studies are still open/opening:
Chiron Study A to Z Study
Argis(Argatroban) Study
Artist Study
AT3 Study
Baxter r-AHF-PFM Study
Cardiology- Fenoldopam Study
Carperitide Study
Corlopam Study
Covance(diabetic foot) Study
Cubist Pneumonia Study
Innohep study
Relax Study
Dr. Wang’s heparin/reopro Stroke Study
Voriconazole Study(compassionate use)