University Hospital Pharmacy Update: June 1987 v. 2, no. 5

Transcription

1 Boston University OpenBU BU Publications University Hospital Pharmacy Update University Hospital Pharmacy Update: June 1987 v. 2, no. 5 Boston University Medical Center The University Hospital, Department of Pharmacy at Boston University Medical Center Boston University

2 B O S T O N U N I V E R S I T Y M E D I C A L The University Hospita. l»iiatb A Newsletter of Current Topics from the Pharmacy Volume 2, Number June Written By: Carol J. Tiani, R.Ph., Pharmacist, The University Hospital Terfenadine (Seldane) represents a new antihistamine class which, unlike common antihistamines, distinguished by the fact that it does not produce sedation like other antihistamines. It is promoted for the treatment of allergic rhinitis and urticaria. Antihistamine agents can be classified into seven different classes. They are alkylamines (i.e. chlorpheniramine, brompheniramine), ethanolamines (i.e. diphen- The University Hospital Formulary Now Available in Print The University Hospital Formulary has recently been published for the first time in over 20 years. The Formulary describes the drugs stocked in The University Hospital Pharmacy, as well as other pertinent information related to the Pharmacy Department and the Pharmacy and Therapeutics Committee of the Medical Staff. The Formulary is divided into three color coordinated sections. The first section (yellow) describes procedures related to the Department of Pharmacy as well as dosing nomograms for aminoglycosides and vancomycin. The second section (white) lists the drugs which can be ordered at The University Hospital by therapeutic classification, including dosage forms and strengths available. The last section (green) is an alphabetical index of drugs by generic and trade names as well as common drug groups. The Formulary are available in 3 ring binders on each Nursing Unit and in the Pharmacy. These formularies will be updated monthly by the Department of Pharmacy and are available for use by all physicians, nurses and unit secretaries. Pocket size versions of the Formulary are available from the Pharmacy for all members of the medical staff upon request. hydramine, clemastine), ethylenediamines (i.e. tripelennamine, pyrilamine), piperidines (i.e. cyproheptadine, diphenylpyraline), piperazines (i.e. cyclizine, meclizine), phenothiazines, (i.e. promethazine) and miscellaneous (i.e. terfenadine). Table 1 lists available antihistamine agents and their formulary status at The University Hospital. Table 1: Antihistamine Agents Antazoline Brompheniramine Chtoipheniramine* Cyproheptadine Diphenylpyraline Methdilazine Terfenadine* Tripelennamine* Azatadine Carbinoxamine Clemastine Diphenhydramine* Doxylamine Promethazine Trimeprazine Triprolidine * Signifies Formulary Agent at The University Hospital (Continued on next page) Index UH Formulary Now Available in Print Residency Program in Hospital Pharmacy Starts P&T Committee Actions Important Notes for House Staff & Nurses... Published by The University Hospital, Department of Pharmacy, 75 E. Newton Street, Boston, MA

3 (Continued from page 1) Pharmacology Terfenadine is a derivative of butyrophenone and is structurally unrelated to other available antihistamine agents. However all antihistamines share a core ethylamine structure. The classes of antihistamine differ in the chemical groups that attach to the core ethylamine structure. Terfenadine is a selective histamine H1 antagonist that appears to have a dual effect on the receptors. It competitively inhibits histamine at its receptor site at low plasma concentrations while an irreversible inhibition of histamine is observed at high concentrations. It does not block the effects of histamine once they have been initiated. Structural similarities between histamine and other biogenic amines (i.e. acetylcholine, 5-hydroxytryptamine, epinephrine and norepinephrine) can result in cross reactions of antihistamines at other receptor sites. These interactions can result in antiserotonergic, antiadrenergic and anticholinergic effects. Terfenadine possesses little antiserotonergic or antiadrenergic activity at normal doses. During clinical trials comparing terfenadine with other antihistamine agents, the incidence of anticholinergic effects (I.e. dry mouth) was similar for all agents. Terfenadine does not cross the blood-brain barrier well. As a result, interaction with H1 receptors in the brain is less likely to occur than with classic antihistamines which cross the blood-brain barrier more readily. This effect may account for the decreased sedation observed with terfenadine. Pharmacokinetics Terfenadine is well absorbed following oral administmiohltowevefttt undergoes extensive first pass metabolism in the liver and less than one percent reaches the circulation unchanged. Its effects begin within one to two hours after oral administration, are maximal within three to six hours and last for greater than 12 hours. Its half life is between 16.1 to 22.7 hours.., ^. ^. Tissue distribution in man has not been determined, however, following oral administration in rats and dogs, the highest concentrations of terfenadine were found in the liver and lung. The lowest concentration was found in the brain which suggests that terfenadine does not penetrate the blood-brain barrier well. Terfenadine is greater than 9 7 % bound to plasma proteins. Terfenadine undergoes extensive first pass metabolism in the liver to primarily two metabolites. The first metabolite is a carboxylic acid analog of terfenadine and possesses one third of the efficacy of the parent drug. The second metabolite is a piperidine carbinol derivative and is inactive. Other metabolites have been detected, but their structures have not been determined. Terfenadine is excreted in the urine and feces as inactive metabolites. Approximately 6 0 % of terfenadine is excreted in the feces, with the remaining 0 % eliminated in the urine. Clinical Efficacy Terfenadine is indicated for treatment of seasonal allergic rhinitis symptoms including sneezing, rhinorj J i e a a n d pruritus. ^ Kemp and colleagues conducted a multicenter, double-blind randomized study to compare the effectiveness of terfenadine, chlorpheniramine and placebo in seasonal allergic rhinitis and conjunctivitis. A total of 397 patients with symptoms of seasonal allergic rhinitis and conjunctivitis were enrolled in this study. All patients had a history of allergic rhinitis responsive to antihistamine therapy during the same season for the previous two years. Doses used were terfenadine 60 mg twice daily, chlorpheniramine mg three times a day and placebo three times a day. All tablets were identical and the noon dose of terfenadine was a placebo tablet so all medications were administered on a three times daily basis. Patients were instructed to take one tablet three times daily for seven days. The physician's assessment of terfenadine revealed that terfenadine and chlorpheniramine were equally efficacious in relieving the symptoms of allergic rhinitis. Both antihistamine agents were significantly beiterthan piaceboirnreating anergic rhmmsr Moderate to complete relief was achieved in 6 0 % of terfenadine or chlorpheniramine treated patients, while only 3 0 % of placebo treated patients had relief of their symptoms. Patient assessment of therapy revealed that both terfenadine and chlorpheniramine provided relief from symptoms on the first day of therapy. Further symptom improvement was noted on continued treatment with either antihistamine agent. Adverse effects were generally mild and incidences were similar for the three groups. The most common side effects were drowsiness/sedation, headache, fatigue and dry mouth. The incidence of drowsiness/sedation was highest in the chlorpheniramine group with 18.8% experiencing these ef-

4 (continued from page 2) fects. The incidences were similar for terfenadine and placebo treated patients at 7.6% and 2.% respectively. Headache was most comnrranly observed in the placebo treated group (1.5%), followed by the terfenadine treated group (9.2%) and the chlorpheniramine treated group (6.5%). Fatigue was observed in.3% and 1.5% of the chlorpheniramine and terfenadine treated groups, respectively. Dryness of the mouth, nose, throat and lips was observed in 5. 1 % of the chlorpheniramine treated group compared to.6% of the terfenadine treated group. Kemp and colleagues concluded that terfenadine and chlorpheniramine were equally efficacious in treating symptoms of allergic rhinitis. The incidence of sedation with terfenadine was similar to that of placebo & significantly less than chlorpheniramine. Kemp followed this study with an open-label study which evaluated the effect of terfenadine 60 mg twice daily on seasonal allergic rhinitis. One hundred fifty-four patients received terfenadine for up to 11 weeks of therapy. Less than 10% of patients required decongestant therapy to alleviate symptoms of allergic rhinitis. Terfenadine provided moderate to complete relief for the length of treatment. The most common adverse effect was headache which was observed in 27.9% of patients. Dry mouth, nose or throat was reported by 6. 1 % of patients while gastric irritation or abdominal cramps were felt by 5.0% of patients. Muscular pain was noted in 3.% of patients and increased appetite was reported by 2.8% of patients. Drowsiness or sedation was only reported in 2.8% of patients receiving terfenadine. Clinical tolerance to terfenadine was not observed during this study. Backhouse et al. conducted a double-blind, randomized, parallel study using 132 patients to compare terfenadine (60 mg twice daily), chlorpheniramine (8 mg twice daily) and placelx) (twice daily). Patients and physicians evaluated the efficacy of both antihistamines. Results were similar for both antihistamine agents and both were superior to placebo in relieving symptoms of allergic rhinitis. Sedation was observed in only one patient treated with terfenadine versus 2 5 % of patients receiving chlorpheniramine. Adverse Effects Adverse effects reported with the use of terfenadine are generally mild and occur infrequently. The most common reactions affect the central nervous system and are reported in 5 to 16% of patients. They include headache, drowsiness, fatigue, sleepiness and tiredness. Other effects may include nervousness, dizziness and weakness. Gastrointestinal effects have been reported in five to eight percent of patients. These effects range from abdominal distress, vomiting and nausea to increased appetite and weight gain. Anticholinergic effects have been reported in less than five percent of patients. These effects include dry mouth, nose, throat and lips. The incidence of these effects is comparable to other antihistamine agents. Other adverse effects have been observed in less than one percent of patients receiving terfenadine. They include skin eruptions, pruritus, alopecia, wheezing, bronchospasm, and sweating. Tachycardia and visual disturbances have been reported with terfenadine use. Drug Interactions There have not been any reported drug interactions in the literature. However, since terfenadine is highly protein bound, there is the potential for displacement from its protein binding site by another highly protein bound drug (i.e. aspirin). Dosage and Administration Terfenadine (Seldane) is available as 60 mg tablets. The usual dose of terfenadine is 60 mg twice daily for the symptomatic relief of allergic rhinitis. The costs of antihistamines on the Formulary at The University Hospital are presented in Table 2. Conclusion Terfenadine represents a new class of antihistamines that has less sedation than the classic agents. Terfenadine's effect as an antihistamine is comparable to the older classic antihistamines (i.e. chlorpheniramine). The decreased incidence of sedation may improve patient compliance. However the excessive cost of terfenadine when compared to older antihistamines is undesirable. Physicians should reserve terfenadine for patients in whom sedation is a critical issue. References Available Upon Request Table 2: Cost Comparison of Antihistamine Agents Aoent Chlorpheniramine Diphenhydramine Terfenadine Dosing Regimen mg qh 50 mg q6h 60 mg BID Cost/7 Davs $0.6 $1.12 $5.75

5 Residency Program in Hospital Pharmacy Initiated. The University Hospital Department of Pharmacy starts its first class for its Residency Program in Hospital Pharmacy on June 29th. The program is designed for graduate pharmacists (NOT students!) to provide experience and training in all aspects of hospital pharmacy practice (distributive, clinical and administrative). The program heavily emphasizes clinical experience in the use of drugs. Residents will participate in work and attending rounds on various medical and surgical services as well as various drug information services of the Department. Experience provided is considered to be equivalent to 3-5 years of on-the job training. Residents are selected as part of a national matching program, an generally represent the top 10% of their class. The program is currently undergoing accreditation by the American Society of Hospital Pharmacists, and represents only 1 of 3 such programs in the Boston area (Brigham & Women's Hospital and New England Medical Center are the other two). Only Pharmacy Departments meeting the most stringent of service requirements are permitted to conduct residency programs. Jen J. Yeh, a Doctor of Pharmacy graduate of the Massachusetts College of Pharmacy, and David Nicolau, a pharmacy graduate of the Northeastern University College of Pharmacy, are the first two residents selected to participate in The University Hospital program. Your cooperation in assisting these two pharmacy residents in their training experiences, and welcoming them to The University Hospital family is appreciated. The University Hospital Department of Pharmacy 75 East Newton Street Boston, MA P&T Committee Actions May 1987 Alan Sugar, M.D. and Thomas Parrino, M.D., were appointed to the Committee. The concept of an Antibiotic Order Sheet was approvedby the Committee. Alfa Interferon 2b, up for its 6 month review, was approved for permanent addition to the Formulary. Important Notes for House Staff & Nurses Nurses and physicians should not tiorrow drugs from BCH or other hospitals^ireetfyr~t1=»e^fhwrriaeyarvhfflot^t^ so borrowed. If a drug is needed, the Pharmacy should be contacted to obtain the drug It should be remembered that the Pharmacy is closed from 11:30PM to 7:00AM. All new orders, especially chemotherapy, should be received by the Pharmacy by 10PM to assure they can be processed prior to closing. Cephapirin, Cephalothin and Cefazolin are considered therapeutic equivalents at The University Hospital. Of these, only Cefazolin will now be stocked by the Pharmacy. The other two drugs will be considered non-formulary. Cefotaxime (Claforan), Ceftizoxime (Ceftizox), and Ceftriaxone (Rocephin) are considered therapeutic equivalents at UH. Ceftizoxime will now be the drug of this group stocked by the Pharmacy. Ceftriaxone will be restrictred to IM and outpatient chemotherapy clinic use only. Cefotaxime will be considered non-formulary.