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                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            | Pharmacy UpdateMarch/April 1997                                                                                                                                                                                                                                                                                                                                       
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|In This Issue

         Cyclosporine for
         Microemulsion

         Medication
         Utilization Evaluation: Omeprazole

         Formulary
         Update

         Did You
         Know...

         
                
                Pharmacy Update Archives
                Drug Information
         Service

         Pharmacy Department

         Warren G. Magnuson Clinical Center

         National Institutes of Health

         Bethesda, Maryland 20892-1196

         Charles E. Daniels,
         Ph.D.

         Chief, Pharmacy Department

         Editor-in-ChiefKarim Anton Calis, Pharm.D., M.P.H.

         Coordinator, Drug Information Service, and Endocrinology
         Clinical Pharmacy Specialist[email protected]

         Associate
         EditorIris P. Masucci, Pharm.D.

         Specialized Resident in Drug Information Practice and
         Pharmacotherapy | Cyclosporine for Microemulsion
         (Neoral®)

         Cyclosporine (Sandimmune®) is an immunosuppressive
         agent that is widely used in solid organ and bone marrow
         transplants as well as in a variety of autoimmune disorders.
         The oral form of Sandimmune® has incomplete and variable
         absorption making it difÞcult to achieve a stable oral
         dosing regimen. Neoral® (cyclosporine for microemulsion)
         is a new formulation of cyclosporine that was approved in
         1995. It was developed to improve the drug's absorption
         characteristics after oral administration.

         Description:Neoral® (cyclosporine for microemulsion)
         is an oral formulation of cyclosporine that immediately
         forms a microemulsion in an aqueous environment. It is
         manufactured by Novartis Pharmaceuticals (formerly Sandoz
         Pharmaceuticals), and is available as 25 mg and 100 mg soft
         gelatin capsules, and as a 100 mg/mL oral solution.

         Indications:
         Cyclosporine (both formulations) is indicated for the
         prophylaxis of organ rejection in kidney, liver, and heart
         allogeneic transplants. Cyclosporine has been used in
         combination with azathiaprine and corticosteroids.

         Pharmacology:
         Cyclosporine is a potent immunosuppressive agent. It has
         been demonstrated to suppress some humoral immunity and to a
         greater extent, cell-medicated immune reactions such as
         allograft rejection, delayed hypersensitivity, experimental
         allergic encephalomyelitis, Freund's adjuvant arthritis, and
         graft vs. host disease in many animal species for a variety
         of organs. Cyclosporine produces speciÞc and
         reversible inhibition of immunocompetent lymphocytes in the
         G0- and G1-phases of the cell cycle.

         T-lymphocytes are preferentially inhibited. The T-helper
         cell is the main target, although the T-suppressor cell may
         also be suppressed. Cyclosporine also inhibits lymphokine
         production and release, including interleukin-2.1

         Pharmacokinetics: After oral
         administration of the standard formulation of cyclosporine
         (Sandimmune®), an oil-in-water droplet mixture is formed
         on contact with gastrointestinal þuids.
         EmulsiÞcation of this mixture by bile salts is
         required before digestion of the oily droplets and release
         of cyclosporine. This emulsiÞcation step is what makes
         the absorption of cyclosporine dependent on bile þow,
         food intake, and gastrointestinal motility, and therefore
         unpredictable. On contact with gastrointestinal þuids,
         Neoral® forms a homogenous, monophasic microemulsion
         which mimics the mixed micellar phase of cyclosporine
         absorption seen with the standard formulation.2

         Neoral® is more rapidly and consistently absorbed
         than Sandimmune® and its relative bioavailability is
         larger. As a result, trough cyclosporine blood
         concentrations can be more closely related to total drug
         exposure during a dosage interval than with Sandimmune®.
         The pharmacokinetic parameters of Neoral® are less
         affected by food than those of Sandimmune®.3

         Cyclosporine is distributed in the plasma, erythrocytes,
         lymphocytes, and granulocytes. In the plasma, cyclosporine
         is approximately 90% bound to proteins. Cyclosporine is
         metabolized by the cytochrome P450 III-A enzyme system in
         the liver and, to a lesser degree, in the gastrointestinal
         tract and the kidney. It is metabolized to at least 25
         metabolites. Neoral® has a half-life of 8.4 hours, with
         a range of 5 to 18 hours. Excretion is primarily biliary
         with only 6% of the dose excreted unchanged in the urine.
         Renal failure or dialysis do not signiÞcantly alter
         cyclosporine clearance.1

         Neoral®, when compared with Sandimmune®, has
         increased bioavailability, decreased intra- and
         inter-individual variability of pharmacokinetic parameters,
         greater correlation between pharmacokinetic parameters and
         for trough concentration relationship, and reduced
         sensitivity to the effects of food on
         absorption.2-4

         Clinical
         Experience: Several studies comparing the two
         oral formulations of cyclosporine in renal and liver
         transplant recipients conÞrm that Neoral® is as
         safe and well tolerated as Sandimmune® for long-term
         maintenance treatment. Neoral® also compared favorably
         to Sandimmune® with regards to graft function.

         Adverse
         Effects: The principal adverse reactions
         associated with cyclosporine are renal dysfunction, tremor,
         hirsutism, hypertension, and gum hyperplasia. Other adverse
         reactions include hypomagnesemia, nausea, vomiting, and
         rarely seizures.

         Drug
         Interactions: Cyclosporine is extensively
         metabolized in the liver by cytochrome P-450 III-A
         microsomal enzymes. Substances that inhibit this enzyme
         system can decrease cyclosporine metabolism and increase its
         blood concentrations. Substances that are inducers of
         cytochrome P-450 activity can increase cyclosporine
         metabolism and decrease its blood concentrations. Several
         drugs are known to act on this enzyme system. Drugs that
         increase cyclo-sporine concentrations include verapamil,
         diltiazem, ketoconazole, itracona-zole, erythromycin, and
         clarithro-mycin. Drugs that decrease cyclosporine levels
         include rifampin, phenytoin, phenobarbital, and
         carbamazepine. Monitoring of cyclosporine concentrations and
         appropriate dosage adjustment are essential when these drugs
         are used concomitantly.

         Concomitant use of nephrotoxic drugs (such as
         amphotericin, aminoglycosides, and vancomycin) may
         potentiate the renal dysfunction of cyclosporine. Careful
         monitoring of renal function should be practiced when these
         agents are used with cyclosporine.

         Precautions and
         Contraindications: Neoral® is
         contraindicated in patients with hypersensitivity to
         cyclosporine or to any of the ingredients of the
         formulation.

         Cyclosporine can cause nephrotoxicity and hepatoxicity
         when used in high doses. Cyclosporine is rated as Pregnancy
         Category C. In animal studies it was embryo- and feto-toxic.
         In case reports of pregnant women (most of whom were
         transplant recipients), most pregnancies had complications
         including: premature birth, low birth weight, pre-eclampsia,
         eclampsia, abrupto placentae, oligohydramnios, Rh
         incompatibility, and fetoplacental dysfunction.
         Malformations were also reported in 5 viable infants.
         Therefore, the risks and beneÞts of using cyclosporine
         during pregnancy should be carefully weighed.

         Dosage and
         Administration: The daily dose of Neoral®
         should always be given in two divided doses. Neoral®
         should be administered on a consistent schedule with regard
         to the time of day and in relation to meals. To make
         Neoral® oral solution more palatable, it should be
         diluted, preferably with orange or apple juice that is at
         room temperature. Grapefruit juice alters the metabolism of
         cyclosporine and should be avoided. The combination of
         Neoral® oral solution and milk can be unpalatable.

         Conversion from Sandimmune® to Neoral®: The
         Pharmacy and Therapeutics Committee recently approved a
         proposal to change the oral formulation of cyclosporine
         available at the Clinical Center from Sandimmune® to
         Neoral®. Sandimmune® and Neoral® are not
         interchangeable, and patients should be monitored closely
         when therapy is changed.

         All Clinical Center patients for whom cyclosporine
         therapy is indicated should be started on the Neoral®
         formulation. All patients who are currently on
         Sandimmune® should be switched to Neoral® with their
         next prescription reÞll. The following guidelines
         should be followed for conversion:

         Start Neoral® at the same daily dose as was
            previously used with Sandimmune® (1:1 dose
            conversion). If the patient is suspected of having
            malabsorption, the better absorption proÞle of
            Neoral® should be taken into consideration.
            Neoral® should always be prescribed for twice daily
            (q12h) dosing.Monitor cyclosporine blood trough concentrations
            every 4 to 7 days after conversion, and adjust the
            Neoral® dose until the level equals the
            pre-conversion value.Monitor clinical safety parameters such as serum
            creatinine and blood pressure every two weeks during the
            Þrst two months after conversion.Cost: The
         table below summarizes the acquisition costs of the
         available forms of cyclosporine. Costs are based on the
         federal supply schedule.

         Agent25
                  mg capsule100 mg capsuleOral solutionSandimmune®$22.61/box of 30$90.97/box of 30$151.45/50 mlNeoral®$24.17/box of 30$96.38/box of 30$160.23/50 mlConclusions:
         Neoral® is an improved oral formulation of cyclosporine.
         It appears to be equal to Sandimmune® in terms of safety
         and efÞcacy. Neoral® offers the advantage of more
         complete and consistent absorption which may, in some cases,
         allow for decreased cyclosporine doses and a decreased need
         for blood level monitoring. Patients who are switched from
         Sandimmune® to Neoral® should be closely monitored.

         References

         Neoral®package insert. Sandoz Pharmaceuticals Corporation.
            September 1995.Noble S, Markham A. Cyclosporin: A
            review of the pharmacokinetic properties, clinical
            efÞcacy and tolerability of a microemulsion-based
            formulation. Drugs 1995;59:924-41.Holt DW, Mueller EA, Kovarik JM et
            al. The pharmacokinetics of neoral: A new oral
            formulation of cyclosporine. Transplant Proc
            1994;26:2935-9.Kahan BD, Dunn J, Fitts C et al.
            Reduced inter- and intra-subject variability in
            cyclosporine pharmacokinetics in renal transplant
            recipients treated with a microemulsion formulation in
            conjunction with fasting, low-fat meals, or high-fat
            meals. Transplantation 1995;59:505-11.Niese D, Buchholz B, Land W et al. A
            double-blind randomized study of Sandimmun Neoral versus
            Sandimmun in new renal transplant recipients: Results
            after 12 months. Transplant Proc 1995;27:1849-56.Frei U, Taesch S, Niese D et al. Use
            of sandimmun neoral in renal transplant patients.
            Transplant Proc 1994;26:2928-31.Levy G, Altaif I, Rezieg M et al.
            Cyclosporine neoral in liver transplant recipients.
            Transplant Proc 1994;26:3184-7. |                                                                                                                                                                                                                                                                                                                                                                       
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|Agent                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    | 25
                  mg capsule                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   | 100 mg capsule                                                                                                                                                                                                                                                                                                                                                        
|                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
|Sandimmune®                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              | $22.61/box of 30                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  | $90.97/box of 30                                                                                                                                                                                                                                                                                                                                                      
|Neoral®                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  | $24.17/box of 30                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  | $96.38/box of 30                                                                                                                                                                                                                                                                                                                                                      
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|Up to Top                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                | Medication Utilization Evaluation:
         Omeprazole (Prilosec®)

         Omeprazole (Prilosec®) is a substituted benzimidazole
         compound with potent antisecretory properties. It suppresses
         gastric acid secretion by inhibiting the H+/K+ ATPase enzyme
         system (proton pump) at the surface of the gastric parietal
         cell. Omeprazole has been available at the Clinical Center
         since 1989. Use of omeprazole at the Clinical Center has
         gradually increased as the number of approved indications
         for the drug has increased. In Þscal year 1995,
         omeprazole accounted for $279,177 of the Pharmacy
         Department's drug budget.

         The Pharmacy and Therapeutics Committee in cooperation
         with the NIDDK Digestive Diseases Branch recently approved
         guidelines for the use of omeprazole. The following
         indications were considered appropriate justiÞcations
         for use of omeprazole at the Clinical Center:

         Endoscopically proven gastric ulcer refractory to
            treatment for 8 weeks with histamine H2-receptor
            antagonistEndoscopically proven duodenal ulcer refractory to
            treatment for 8 weeks with histamine H2-receptor
            antagonist or sucralfateEndoscopically proven grade 3 or 4 reþux
            esophagitisEndoscopically proven reþux esophagitis
            refractory to treatment for 3 months with histamine
            H2-receptor antagonistHypersecretory conditions (e.g., multiple endocrine
            adenomas, systemic mastocytosis, Zollinger-Ellison
            Syndrome)Endoscopically proven Barrett's esophagusHelicobacter pylori eradication in conjunction with
            antimicrobial agentsThe Pharmacy and Therapeutics Committee undertook a
         review of omeprazole use at the Clinical Center.

         Methods: A
         retrospective review of medical records was conducted. A
         search of the hospital's Medical Information System was used
         to identify patients (inpatients and outpatients) who had
         received omeprazole between January and April of 1996. The
         Þrst 100 records were reviewed. Basic demographic data
         regarding patients and prescribers were collected.
         Additionally, information about the indication for
         omeprazole use and dosage regimen were collected.
         Information about medication-related adverse effects was not
         collected because of the limitations of retrospective
         reviews.

         Results: Of
         the 100 medical records reviewed, only 75 contained
         sufÞcient documentation about omeprazole to be
         considered evaluable. In each of these cases, omeprazole was
         prescribed appropriately for indications consistent with the
         Clinical Center guidelines. The dosage regimen in all of
         these cases was also appropriate. Fifty-Þve of the
         orders were for patients with various hypersecretory
         conditions (mostly Zollinger-Ellison Syndrome). Sixty-two of
         the omeprazole orders were prescribed by physicians from the
         National Institute of Diabetes and Digestive and Kidney
         Diseases.

         Conclusions:
         Omeprazole prescribing, where clearly documented in the
         medical record, is appropriate. The dosing regimens and
         indications for use are consistent with accepted guidelines.
         The indications for omeprazole use are not always clearly
         documented in the medical record. Clinicians should be
         familiar with the Clinical Center's guidelines for
         omeprazole use and clearly document the indication for
         omeprazole (and other medications) in the medical record.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
|Up to Top                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                | Formulary Update

         The Pharmacy and Therapeutics Committee recently approved
         the following formulary actions:

         Additions

         Albendazole (Albenza), a broad-spectrum, oral
            antihelmintic agentCisatracurium (Nimbex®), an intermediate acting,
            non-depolarizing neuromuscular blockerRemifentanyl (Ultiva®), a short-acting, mu-opioid
            receptor agonistElliott's B solution, a vehicle for intrathecal drug
            administrationInsulin lispro (Humalog®), an anlog of regular
            human insulinTestosterone transdermal system (Androderm®)Cyclosporine (Neoral®)Clomiphene (Clomid®), an ovulation stimulantDeletions

         Nadolol (Corgard®)Propoxyphene (Darvon®)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
|                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         | Did You Know...

         The FDA approved a record 53 new molecular entities in
         1996. Of these, 47 are for therapeutic use and 6 are
         diagnostic agents.

         Donepezil (Aricept®) has been approved for the
         treatment of mild to moderate Alzheimer's disease. This
         agent joins tacrine (Cognex®) as the only agent
         sapproved for the treatment of this disease.

         Two new once-daily oral quinolones have recently been
         approved by the FDA Sparþoxacin (Zagam®) is
         indicated for use in the treatment of community-acquired
         pneumonias and bacterial exacerbations of bronchitis.
         Levoþoxacin (Levaquin®) was approved for use in
         respiratory tract infections as well as certain skin,
         kidney, and urinary tract infections. It is also available
         in a parenteral formulation.

         Somatropin [rDNA origin] (Nutropin®) recently gained
         approval for the treatment of growth failure associated with
         Turner syndrome.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
|Up to Top                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                | Editor's Note
         

         We wish to thank Cynthia Dunbar, M.D. for reviewing the
         article on cyclosporine, and acknowledge Michelle Plante,
         Pharm.D. and Melissa Johnson, Pharm.D. for their
         contributions to this issue of Pharmacy Update.

         Designed by Richard Barnes, NCRR, MAPB.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           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