……………For Your Drug Information ………….

1). Xyrem® (gamma hydroxybutyrate, GHB) – for treatment cataplexy associated with narcolepsy. The FDA plans to tightly control the distribution of the drug because of the high risk of abuse. It will be a schedule III medication. The studies used two 9-gram doses, which must be spaced 2.5 to 4 hours apart. The medication will be supplied as an oral liquid. Drug is manufactured by Orphan Medical Inc.

2). Zelnorm® (tegaserod maleate) – oral medication used for the short-term treatment of women with irritable bowel syndrome, whose primary bowel symptom is constipation. The drug is supplied by Norvartis Pharmaceuticals Corp. and is recommended to be taken as 6 mg BID, before meals, for 4-6 weeks.The drug may be used for an additional 4-6 weeks for those patients with good response. The drug’s effect on men has not been determined. The drug is the first in a new class of drugs, the serotonin type-4 receptor agonists. Activation of the serotonin type-4 receptors stimulates the peristaltic reflex. It has no affinity to seratonin type-3 or dopamine receptors.

3.) LotronexÒ (alosetron) – oral agent marketed for the treatment of irritable bowel syndrome. It was withdrawn from the market early this year due to severe gastrointestinal toxicity (constipation, bowel obstruction, bowel ischemia, perforation and death). The FDA allowed this drug to be reintroduced but at a lower dosage, a narrower indication and restricted marketing. Indicated ONLY for women with severe diarrhea-type IBS who have chronic symptoms (>6months) that are not due to anatomic or metabolic abnormality and who have failed conventional therapies. The new starting dose is 1mg po daily x 4 weeks and may be increased to a max dose of 1mg po bid. If patient do not adequately respond after 4weeks of the higher dose, the drug should be discontinued.

1). Does Lantus® (insulin glargine) have to be given at bedtime? Per personal communication with Aventis Pharmaceuticals medical information hotline, one of the original studies conducted with Lantus® showed that patients had slightly overall better blood sugar control with evening versus morning administration. Subsequently, clinical trials for Lantus® were done with the bedtime dosing and therefore the drug was FDA approved with that specific administration time in the package insert. If you were to base dosing on 24 hour kinetics, time of administration probably is not that critical. Aventis Pharmaceuticals® suggested that administration times may be adjusted based on clinical response, patient convenience, or patient preference. Some small studies are currently being conducted to check the efficacy of Lantus® with various times of administration. (Personal communication with Aventis Pharmaceuticcals 8/8/2002, memo located in drug information files - Insulins).

2). Are there alternate antibiotic choices for patients who have methicillin-resistant staphlococcus aureus (MRSA) skin-soft tissue infections, pneumonia who require home IV therapy with Vancomycin? A recent article in Clinical Infectious Diseases offered a possible alternative antibiotic choice for patients who may require home IV therapy with vancomycin. In this open label study, patients were randomized to receive either linezolid (ZyvoxÒ ) or vancomycin for the treatment of documented MRSA (NOTE: one of the exclusion criteria was osteomyelitis) infections. Oral linezolid has 100% bioavailability and patients could be switched to the oral form of the medication.

3.) How is XigrisÒ dosed in obese patients? Dose using the actual body weight – per Lilly personal communication.

4.) How does one perform a two-step PPD testing? Some patients who were positive years ago may have a false negative reaction due to their waning skin test response. However, subsequent PPD test may boost this reaction and may be misinterpreted as a recent converter or recent infection. Persons which may experience this boosting effect include: those exposed and are 55 yrs or older, or previously vaccinated with BCG The two-step PPD testing is recommended to address this problem. Procedure:

1. Administer PPD skin test
2. If negative and a negative PPD skin test has not been documented for the past 12 months, administer a second test (1-3 weeks later).
3. If 2^nd test is negative – consider uninfected; If 2^nd test is positive – consider infected --- use this second test as the baseline result.

** repeated PPD skin testing does not, by itself, boost reactions in individuals without TB infection or BCG vaccination.

5.) Information for "BCG lozenges" for treatment of radiation mucositis.

BCG = 6mg Bacitracin, 10mg Clotrimazole, 2mg Gentamicin lozenges ; Pilot study on this found in Antimicrobial Lozenge in Radiation – induced mucositis. ( Head and Neck January 2002. pg 6 –15). Study done in Canada.

6.) MD wants Flomax® or Hytrin® to be administered via NG tube – wants information if possible.

Flomax® can not be broken, crushed, chewed or opened because it is an extended release form. Hytrin® may be OK.. (Am J Health Syst Pharm. 1995 September; 52(18):2031

Procedures are as follows –

Dissolve terazosin capsule in 60ml warm water (100 – 110 ^◦ F); Stir until shell ruptures. Stir until a homogenous solution results ( 5-10min).Solution may be colored depending on the capsule color. Draw up entire solution with oral syringe and flush into NG tube/ feeding tube. Flush the tube with water.

7.) Cyctotec ® (misoprostil) rectal administration? Cytotec can be dissolved in saline and administered as a rectal enema for treatment of postpartum hemorrhage or it can be administered intravaginally (as a tablet) for abortion, cervical priming , cervical ripening and labor induction. ( Drugdex 2002 – Cytotec) . It may be comparable to Cervidil as an abortifacient, cervical primer / labor inducer. It may be less desirable when compared to oxytocin for postpartum hemorrhage due to increased side-effects and higher cost.

** If orders for misoprostil (Cytotec) is received for a woman of childbearing age , please verify that she is not pregnant.

8.) Percutaneous ethanol injection in the treatment of hepatocellular carcinoma? Percutaneous ethanol injection (PEI) is another treatment alternative to surgical resection in patients with hepatocellular carcinoma. (Dig Dis 2001;19:292-300)

Itraconazole is synthetic triazole antifungal agent available as an injection, oral solution, and capsules. The capsules and injection are available at OSF Saint Francis. Itraconazole injection/oral solution is indicated for empiric therapy of febrile neutropenic patients with suspected fungal infections. Itraconazole injection is indicated for the following fungal infections in immune and non-immune compromised patients:

• Blastomycosis, pulmonary and extrapulmonary
• Histoplasmosis, including chronic cavitary pulmonary disease and disseminated, non-meningeal histoplasmosis; and
• Aspergillosis, pulmonary and extrapulmonary, in patients who are intolerant of or who are refractory to amphotericin B therapy.

Itraconazole Oral Solution is also indicated for the treatment of orophayngeal and esophageal candidiasis.

Itraconazole capsules are also approved for treatment of toenail and fingernail onychomycosis due to dermatophytes.

The absolute oral bioavailability of itraconazole was 55%. Taking the capsules with a full meal provides maximum bioavailability. This is an important fact to keep in mind if converting a patient from oral to injectable itraconazole. Bioavailability is also decreased in patients with relative or absolute achlorhydria. Itraconazole is primarily metabolized by the cytochrome P450 3A4 and requires careful screening for drug interactions when a patient is started on therapy. Less than 0.03% of parent drug are eliminated by renal excretion. Dosage adjustments are not required until the CrCl is <10 ml/min. IV itraconazole can cause a dose-related negative inotropic effect and should be used cautiously in patients with congestive heart failure.

Drug interactions with itraconazole (table is NOT all inclusive):

*Manufacturer has no specific dosing guidelines

Adverse reactions: More common side effects include headache, rhinitis, upper respiratory infections, sinusitus, diarrhea, dyspepsia, mausea, abnormal dreaming, constipation. Itraconazole has been associated with rare cases of serious hepatotoxicity.

Contraindications: Itraconazole capsules should not be used for treatment of onychomycosis in patients with ventricular dysfunction such as found in congestive heart failure. Carefully screen patient’s drug therapy for any potential contraindications due to drug interactions.

Pregnancy Category: Itraconazole is listed as Pregnancy Category C and should only be used for treatment of systemic fungal infections if the benefit clearly outweighs the risk. Itraconazole should not be used in pregnant women for treatment on onychomycosis.

Reference: Package insert Sporanox®, Janssen Pharmaceuticals.

Vanlev® peak concentration is reached in 0.5-2 hours when using the oral route and 0.5 hours when using IV route. Steady state plasma levels were reached in 3 – 4 days. The absolute oral bioavailability of omapatrilat is 20% to 30% and the absorption is not affected by food intake. The liver extensively metabolizes this drug, but it is not inhibited or induced by CYP450. The kidneys excrete 64% (oral) and 80% (IV) and the elimination half-life is 14 – 19 hours in this product. Omapatrilat dose does not need to be adjusted in patients with reduced renal function.

Dosages: Vanlev® has been shown to be effective in treating mild to moderate hypertension when the initial dose of 20 mg PO once a day is used and can be titrated up to a maximum of 80 mg PO once a day. Chronic heart failure has been tested with 2.5 –40 mg PO daily and it has shown to be an effective dosage.

Drug interactions: Drug and food interactions have not been observed with this drug. It is assumed that omapatrilat would have some of the same drug interactions as ACE inhibitors. Some common drug interaction for ACE inhibitors are Allopurinol, Aspirin, Azathioprine, Lithium, Potassium supplements, Potassium sparing diuretics, and Trimethoprim. Drugdex also referenced a study that observed no drug interaction when Warfarin was co-administered with omapatrilat.

Adverse reactions: Omapatrilat is very closely related to ACE inhibitors and it has some of the same adverse effects. Some common adverse effects are hyperkalemia, cough, hypotension, increased SrCr, and dizziness. Dizziness, diarrhea, vision disturbance, hypotension and angioedema are more common with patients taking Vanlev® but patients had fewer exacerbation’s of congestive heart failure and increased SrCr when compared to lisinopril.

Precautions:

-Hypersensitivity to omapatrilat (contraindicated)

-Hypersensitivity to ACE inhibitor

-History of angioedema with prior ACE inhibitor treatment

-Hereditary angioedema

-Hepatic dysfunction

-Coronary insufficiency

-Autoimmune disease

-Renal transplant patients

-Renal failure

-Pregnancy

Comparative studies: ACE inhibitors and calcium channel blockers have been compared with omapatrilat to assess the efficacy in reducing blood pressure. Amlodipine and omapatrilat were compared in mild to moderate hypertensive patients and the average systolic/ diastolic blood pressure reduction in omapatrilat group was significantly greater. A study was done to compare the efficacy of lisinopril and omapatrilat in mild to moderate hypertension patients. One study observed dosages of 5 and 10 mg of omapatrilat were equivalent to 20 mg of lisinopril, 20 and 40 mg doses of omapatrilat had a greater reduction in systolic blood pressure. African-American and Caucasian patients who were treated with omapatrilat had a comparable reduction in blood pressure while African-Americans treated with lisinopril had a lower reduction in blood pressure than Caucasian patients.

Pregnancy Category: Lacking information

Market Availability: Investigational drug status

Reference:

DrugDex drug evaluation 2002

Clinical Pharmacology 2002 monographs: Omapatrilat

Nathisuwan S, Talbert R L. A Review of Vasopeptidase Inhibitors: A New Modality in the Treatment of Hypertension and Chronic Heart Failure. Pharmacotherapy 2002;22(1):27-42.

DTI – 0009 Study Apollo Study

Voriconazole Study (compassionate use) AT3 ECMO Study Artist Study

A-Z study

Baxter r-AHF-PFM - adults

Baxter rAHF-PFM - peds

Corlopam study (Radiology)

CancerVax Melanoma Study

Cardiology – Fenoldopam Study

Carperitide study

DCVax – Prostate Cancer Study

Exclaim Study

Fusion I (natrecor) Study

ISO Study (UICOMP opoid study)

Synergy Study

Dr. Wang’s heparin/reopro Stroke Study