Therapeutic-interchange program for oral histamine H2-receptor antagonists.

A therapeutic-interchange (TI) program for oral histamine H2-receptor antagonists at a hospital is described. In 1992 the pharmacy and therapeutics committee at a large teaching hospital accepted cimetidine as the preferred oral H2 antagonist. However, the program to promote cimetidine met with little success. The manufacturer of nizatidine then offered the hospital that drug at a reduced cost relative to all other members of the drug class. The committee recommended including nizatidine on the formulary; implementing a TI program so that when an order for an oral H2 antagonist was written nizatidine would be dispensed; deleting cimetidine and ranitidine tablets from the formulary; and retaining cimetidine and ranitidine oral liquid and i.v. formulations. The program was approved by the medical executive committee and was implemented in August 1994. Extensive efforts to inform the pharmacy, medical, and nursing staffs about the program were undertaken, and the pharmacy established mechanisms for monitoring compliance. Two months into the program, 97% of eligible patients were receiving nizatidine. Actual cost savings in the first four months exceeded $40,000. In July 1997 the same program was applied to famotidine, which had replaced nizatidine as the most cost-effective H2 antagonist. A successful TI program for oral H2 antagonists was achieved by gaining physician support for the program, educating providers, monitoring compliance, and responding to changes in drug costs.

Hyperkalemia and high-dose trimethoprim/sulfamethoxazole.

Evidence from the literature strongly supports that high doses of TMP, as used in the treatment of PCP in AIDS patients, have the propensity to cause hyperkalemia by inhibiting sodium channels in the distal nephron, thereby impairing potassium secretion. The mechanism of TMP-induced hyperkalemia is believed to be similar to that of triamterene and amiloride because of the structural similarity of these agents. It is also possible that declining renal function, which is a natural progression of HIV disease, may contribute to the hyperkalemia seen in this patient population. In addition, patients with AIDS also may exhibit a defect in adrenal function, potentiating the hyperkalemic effect of TMP therapy. Therefore, it is crucial for clinicians to monitor closely the serum potassium concentration in this patient population, especially during therapy with high doses of TMP.

Pharmaceutical services and inpatient drug costs in bone marrow transplantation.

A survey of U.S. bone marrow transplantation (BMT) programs was conducted to determine the role of pharmaceutical services in those programs and the pharmacy department resources allocated to support them. Surveys were sent to 92 U.S. BMT programs to solicit the following information: characteristics of the institution and the BMT program, extent of pharmacist involvement in the BMT program, and pharmacy resource allocation to the program. Fifty-five responses were received (60% response rate). BMT pharmacists were employed by 53 of these institutions (a total of 66 pharmacists). BMT pharmacists at 49 of the 53 institutions (92%) received their salary from the department of pharmacy. Common BMT pharmacist responsibilities included managing adverse effects (100% of respondents), adjusting medication doses (96%), providing drug information (94%), participating in BMT team rounds (87%), maintaining medication profiles (85%), and developing medication protocols (81%). Inpatient BMT-related drug costs (reported by 37 respondents) averaged 12% of the pharmacy's annual inpatient drug budget. One or more pharmacists were members of the BMT team at 46 of 53 institutions. BMT-related drug costs accounted for 12% of the total inpatient drug budget at the 37 institutions reporting cost data.

The formulary decision-making process in a US academic medical centre.

This article reviews and describes the formulary decision-making process in an academic medical centre. The pharmacy and therapeutics (P & T) committee is the organisational nucleus of the drug use control process in the institutional environment. Thomas Jefferson University Hospital (TJUH), a 720-bed academic medical centre in an urban locality in the US, is used as a model representative of how most of these committees function. Survey responses collected from 29 peer academic medical centres are presented to compare and contrast the structure and function of the P & T committee at TJUH with corresponding procedures in other university hospitals in the US. TJUH is typical of the institutions which comprise the University Hospital Consortium (UHC). The P & T committee of TJUH is composed of 29 members, meets once per month for 10 months of the year, and has a network of 13 subcommittees. TJUH has an intermediately controlled (mixed) formulary, and uses both restricted drugs and treatment guidelines. Of the 29 UHC member institutions responding to the survey, the average P & T membership is 18, the average meeting frequency is 11 times per year, and 83% of these committees have a network of subcommittees. None describe their formulary system as open, 86% have a closed formulary and 14% have a mixed formulary system. There is a restricted drug programme in 76% of the institutions, 79% utilise treatment guidelines, 76% practice therapeutic interchange and all employ generic substitution. Specific areas addressed in this review include the history of the formulary system, the structure and function of the P & T committee, types of formularies, cost containment and the formulary decision-making process, the impact of organisational culture on physician decision making, the role of the pharmacy department, the role of pharmaceutical sales representatives and their impact on prescribing habits, the impact of the Joint Commission on Accreditation of Healthcare Organisations (JCAHO) Agenda for Change on the formulary process, and future challenges.

Adjuvant corticosteroid therapy for Pneumocystis carinii pneumonia in AIDS patients.

OBJECTIVE: To review published abstracts, case reports, and journal articles and evaluate data examining the use of systemic corticosteroids as adjuvant treatment for Pneumocystis carinii pneumonia (PCP) in patients with AIDS. DATA SOURCES: Computerized online databases, peer-reviewed journals from January 1986 through September 1991, and personal communication with a National Institutes of Health correspondent. STUDY SELECTION: The authors identified 13 reports pertinent to this review. By author consensus, five studies were selected for analysis based on sample size, controlled study design, and clinical outcome measures. Recommendations of an expert panel from the National Institutes of Health and the University of California also are discussed. DATA EXTRACTION: Data are presented based on the methodologic strength of the studies reviewed. Studies are assessed on sample size, inclusion criteria, comparative cohort populations, specific patient outcome measures, and statistical analysis. DATA SYNTHESIS: Results of the study analysis support the use of systemic corticosteroids as early adjunctive therapy for AIDS patients with moderate-to-severe PCP who have an initial arterial oxygen partial pressure of less than 70 mm Hg or an alveolar-arterial gradient greater than 35 mm Hg on room air. Improved outcomes included decreased mortality, respiratory failure, and deterioration of oxygenation. Data evaluated have shown that adjuvant corticosteroid therapy is most effective when initiated within 72 hours of beginning specific antipneumocystis therapy. A small, but sometimes significant, increased rate of infection in steroid-treated patients was noted. CONCLUSIONS: Based on the literature reviewed, early systemic adjuvant corticosteroid therapy can benefit patients with moderate-to-severe AIDS-related PCP. The steroid regimen used in the largest controlled trial and recommended by the expert panel is prednisone 40 mg bid (days 1-5), then 40 mg/d (days 6-10), then 20 mg/d (days 1-21).

P & T Committee response to evolving technologies: preparing for the launch of high-tech, high-cost products. Roundtable discussion.

P & T Committees are entering an exciting era in which the introduction of biotechnology-derived pharmaceuticals is providing life-saving opportunities for conditions for which there was little or no hope for a cure. The P & T Committee at Thomas Jefferson University Hospital has anticipated the challenge that these novel therapeutics present, and has already positioned itself for the pending approval of the first therapeutic human monoclonal antibody. Nebacumab (HA-1A, formerly known as Centoxin; by Centocor) will be used for the treatment of gram-negative sepsis. Although this antiendotoxin has a good side effect profile, its use also carries a high price tag. This will raise several difficult ethical issues once the product is introduced. In this exclusive Hospital Formulary roundtable, members of Thomas Jefferson's P & T Committee and Technology Assessment Subcommittee provide their insights for responsibly managing a high-tech, high-cost product such as nebacumab.

Use of intravenous immune globulin therapy: an overview.

The intravenous immune globulin (IGIV) preparations are reviewed with respect to method of preparation, pharmacokinetics, clinical uses (with emphasis on the labeled indications), and adverse reactions; a brief review of the immune system also is provided. IGIV preparations are approved for the treatment of hypogammaglobulinemia, recurrent bacterial infections due to B-cell chronic lymphocytic leukemia, and idiopathic thrombocytopenic purpura (ITP). The mechanism of action in the first two indications is passive replacement of antibodies, but in ITP the mechanism is not clearly established. The clinical literature on the use of IGIV for these indications is summarized. In patients with ITP, platelet counts return to safe levels and the number of infections is reduced in patients with primary humoral immunodeficiency treated with IGIV. The use of IGIV in pregnant women and premature infants is controversial. Adverse reactions are primarily related to infusion rate, activation of complement, and anaphylactic reactions to a component of the product. There is minimal to no risk of viral transmission with IGIV therapy. IGIV also has been administered safely on an outpatient or homecare basis. This has led to a feeling of greater control by patients over their chronic illness. Other uses of IGIV are under investigation. As our understanding of the immune system and the pharmacology of immune globulin increases, the uses of IGIV will expand.

Treatment of Pneumocystis carinii pneumonia in patients with AIDS.

A 44-year-old man with acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia (PCP) who suffered adverse effects from treatment with trimethoprim-sulfamethoxazole (TMP-SMX) and was then treated with pentamidine isethionate is described, and approved and investigational drugs used in the management of PCP in the AIDS patient are discussed. After taking TMP-SMX, 240 mg trimethoprim and 1200 mg sulfamethoxazole, four times a day orally for 10 days at home, the patient was hospitalized complaining of nausea, vomiting, diarrhea, and fever. Intravenous TMP-SMX was begun at a dosage of 18 mg/kg/day of trimethoprim. Four days later, his condition had deteriorated and he had elevations of liver enzymes and a decrease in white blood cell (WBC) count. TMP-SMX was discontinued and pentamidine isethionate was started at a dosage of 4 mg/kg/day i.v. His symptoms and fever subsided and his liver enzyme levels and WBC count improved. After nine days of pentamidine his WBC count decreased; pentamidine was suspected as the cause and discontinued; no further therapy was needed. PCP was the initial infection that established this patient's diagnosis of AIDS. The patient did not have exertional dyspnea and nonproductive cough, which are usually seen in AIDS patients with PCP. TMP-SMX 20 mg/kg/day, based on the trimethoprim content, is the usual initial treatment for PCP. Adverse effects of TMP-SMX develop more frequently in AIDS patients than in non-AIDS patients with PCP. The recommended dose of pentamidine isethionate for the treatment of PCP is 4 mg/kg/day, im. or i.v. A few studies have shown good response to aerosolized pentamidine. Trials of investigational agents have excluded patients with severely compromised respiratory status; eflornithine, dapsone in combination with trimethoprim, and trimetrexate have been used. Corticosteroids should be considered a last effort until additional data are available. TMP-SMX may be used to prevent recurrence of PCP or to prevent the initial occurrence of PCP in AIDS patients. Intravenous or aerosol doses of pentamidine may be effective as prophylaxis. Sulfadoxine-pyrimethamine tried as prophylaxis produced adverse reactions. Despite its higher incidence of serious adverse effects in the AIDS population, TMP-SMX is considered preferable to pentamidine for initial therapy. Pentamidine is preferred for patients with documented allergy to TMP-SMX or failure to respond to a five- to seven-day course of TMP-SMX.

Management of Pneumocystis carinii pneumonia in patients with AIDS and other conditions: experience in a Philadelphia University Teaching Hospital.

We reviewed the records of 49 patients who had 55 episodes of Pneumocystis carinii pneumonia (PCP) from January 1984 to January 1987. Thirty-three patients had acquired immunodeficiency syndrome (AIDS), with the risk groups being homosexual/bisexual practices (26), hemophilia (6), and blood transfusion (1). Fourteen patients had a history of malignancy or chemotherapy and two underwent organ transplantation. Overall response to therapy of PCP was 75% (77% of patients with AIDS, 68% of those with other conditions). All six relapses occurred in patients with AIDS. Both trimethoprim-sulfamethoxazole (TMP-SMX) and pentamidine were associated with a higher rate of toxicity in those patients than in patients with other conditions. A 30% rate of failure due to side effects occurred when TMP-SMX was used as initial therapy, but the combination is considered effective and should be given an adequate therapeutic trial. Pentamidine was an effective alternative for patients who failed with TMP-SMX and for those who failed therapy due to side effects, but was associated with serious toxicities. Our experience was similar in some respects to previous published results from New York and California.

Intravenous immune globulin: dosage and administration.

Intravenous immune globulin (IV-IgG) is approved for use in substitution therapy of immunodeficiency syndromes and treatment of idiopathic thrombocytopenic purpura (ITP). The initial dose for substitution therapy is 0.2 g/kg body weight repeated monthly. If necessary, the dose may be increased to 0.3 g/kg and the frequency to every 2-3 weeks. The approved dosage for ITP is 0.4 g/kg daily for 2 to 5 consecutive days. Repeat doses of 0.4 g/kg have been used as maintenance therapy. The initial infusions of IgG to immunodeficient patients who have not been treated during the previous 8 weeks or never treated at all should proceed with caution. These patients are at risk of potentially serious complement-mediated adverse reactions. Adverse reactions due to IgG administration are less frequent and less severe for patients with ITP. Currently available preparations are contraindicated in patients with a selective IgA deficiency and detectable IgA antibodies.

Immunotherapy of idiopathic thrombocytopenic purpura and autoimmune neutropenia.

Idiopathic thrombocytopenic purpura (ITP) is a disorder characterized by a low platelet count and purpura. Identification of an antiplatelet antibody suggests that this is an autoimmune disease. Corticosteroids and splenectomy have been the major therapies for many years. High-dose intravenous immune globulin (IV-IgG) has been very successful in the management of ITP and has recently received FDA approval for this condition. It was also successful when administered to a few patients with autoimmune neutropenia. The exact mechanism of action of IV-IgG in autoimmune disorders is poorly understood. Currently, high-dose IV-IgG has a definite place in the management of ITP. Its role in therapy includes emergency treatment, preoperative preparation, the postponement of splenectomy in young children, and treatment of ITP during pregnancy.

Treatment of infectious complications of acquired immunodeficiency syndrome.

The infectious complications of the acquired immunodeficiency syndrome (AIDS) are discussed, and the conventional and nonconventional therapies used for these infections are reviewed. The infections most commonly encountered in patients with AIDS are Pneumocystis carinii pneumonia (58%), Candida esophagitis (31%), toxoplasmosis (21%), cytomegalovirus infections (15%), and herpes-simplex virus infections (12%). Pneumocystis carinii pneumonia is the most common life-threatening process in these patients. Trimethoprim-sulfamethoxazole (TMP-SMZ) is considered the drug of choice for its treatment. Oral candidiasis often indicates the progression to AIDS in the high-risk populations of homosexual or bisexual men, intravenous drug abusers, and individuals with hemophilia. Nystatin suspension is commonly used to treat oral candidiasis, while Candida esophagitis demands systemic therapy with ketoconazole. Toxoplasmosis most commonly manifests itself in patients with AIDS as a cerebral mass lesion. The recommended therapy includes sulfadiazine and pyrimethamine. AIDS patients frequently experience protozoal invasion of the intestinal tract with Giardia lamblia, Isospora belli, and Cryptosporidium muris. Various drugs have been tried for these infections, including quinacrine hydrochloride, metronidazole, TMP-SMZ, and spiramycin. Cytomegalovirus (CMV) infections commonly involve the lungs, gastrointestinal tract, eyes, brain, and nervous system. Attempts to treat these disseminated CMV infections with antiviral agents, including acyclovir, have not been successful. However, acyclovir has been found beneficial in the treatment of herpes-simplex virus infections. Multiple infectious complications may occur in patients with AIDS as a result of the cellular-immune deficiency associated with this disease. Until more research is done with AIDS patients, therapy must be based on the data available from the treatment of these infections in immunosuppressed patients without AIDS.

Grand rounds. Immune globulin in the treatment of autoimmune thrombocytopenic purpura.

Two patients with autoimmune thrombocytopenic purpura (ATP) who received high-dose intravenous immune globulin before undergoing splenectomy are described, and the pathogenesis, clinical presentation, diagnosis, and treatment of chronic ATP are reviewed. One patient was a 62-year-old white man who was admitted to the hospital with a history of thrombocytopenia and probable steroid-induced diabetes mellitus. The second patient was a 24-year-old black woman who was admitted for recurrent bleeding episodes and splenectomy. In both patients, immune globulin 1.5 g/kg administered over four to six days resulted in marked elevations of platelet counts. ATP is a platelet disorder of unknown etiology. Platelets with surface-bound antiplatelet antibody are destroyed by the reticuloendothelial system. As the platelet count falls below 30,000-50,000/cu mm, the patient may manifest signs of bleeding such as petechiae, purpura, ecchymosis, menorrhagia, epistaxis, and bleeding from other mucosal surfaces. Corticosteroids are the initial treatment of choice. Splenectomy is considered for children with the life-threatening hemorrhage and for patients who do not respond to corticosteroids. Patients who are refractory to steroid therapy and splenectomy may respond to immunosuppressant agents. Approximately, 80% of patients treated with immune globulin have responded with an increase in platelet count, although this increase is sometimes transient. Immune globulin therapy is recommended for emergency treatment of ATP, as preoperative medication before splenectomy, and for young children in order to postpone splenectomy. Despite a good response to treatment, immune globulin therapy should not be considered a cure for ATP.