bluuebunny/crossref_metadata_2025 huggingface dataset:
Medication-Induced Headache: Overview and Systematic Review of Therapeutic Approaches
Authors: Zed Peter J , Loewen Peter S , Robinson Gordon
Published: March 2004

OBJECTIVE:

To review medication-induced headache (MIH) through a systematic evaluation of the literature regarding the pharmacologic management of this condition.

METHODOLOGY:

To identify and evaluate all pharmacologic interventions for MIH, we conducted a qualitative systematic review of the English-language literature from 1966 to June 1998 using MEDLINE. The following search terms were used: chronic daily headache, transformed migraine, analgesic withdrawal headache, analgesic rebound headache, drug-associated headache, medication-induced headache, detoxification, and dihydroergotamine. In addition, a review of the references from relevant literature was also conducted to collect reports not identified in the MEDLINE search.

RESULTS:

Numerous therapies for acute management of MIH have been evaluated, although no rigorously conducted clinical trials were identified. Therapies evaluated include abrupt withdrawal of analgesics, initiation of dihydroergotamine, nonsteroidal antiinflammatory agents, methylergonovine, dihydroergotamine, sumatriptan, amitriptyline, dexamethasone, piracetam, prothipendyl, and valproate. Epidemiology, diagnosis, clinical features, pathophysiology, and long-term prognosis of therapy are discussed and therapeutic guidelines are offered.

CONCLUSIONS:

MIH is an underrecognized and difficult condition affecting headache-prone patients. The published literature concerning treatment of patients with MIH is scant and of poor quality, making it difficult for clinicians to decide on appropriate therapy. Recognition and treatment of MIH may lead to a long-term improvement in headache relief for many patients. It appears that complete withdrawal of the medications being overused is required for favorable long-term results.
Pyloric Channel Stricture Secondary to High-Dose Ibuprofen Therapy in a Patient with Cystic Fibrosis
Authors: Bell Edward A , Grothe Rayna , Zivkovich Veljko , Foote Jan M , Wellendorf Joyce
Published: March 2004

OBJECTIVE:

To describe a case of pyloric channel stricture secondary to high-dose ibuprofen therapy in a pediatric patient with cystic fibrosis.

CASE SUMMARY:

A 12-year-old white girl started taking high-dose ibuprofen to treat the pulmonary manifestations of cystic fibrosis. The peak plasma concentration at dose initiation was within the accepted therapeutic range. Approximately one month later, the patient developed emesis and intolerance of solid foods, which persisted for several months and resulted in a weight loss of seven kilograms. The patient was referred to a pediatric gastroenterologist, who performed an upper endoscopy and subsequently diagnosed a pyloric channel stricture. The patient's pyloric channel was successfully dilated with two balloons. It is felt that the pyloric stricture developed from healing antral/pyloric channel ulcers. Ibuprofen was discontinued and omeprazole therapy was begun. Over the course of the following year, the patient was asymptomatic. Follow-up upper gastrointestinal barium swallows were normal.

DISCUSSION:

When used for analgesia and fever in the pediatric population, ibuprofen has been shown to be a relatively safe drug. While it is known that ibuprofen may cause gastrointestinal adverse effects, the pediatric population is at lower risk; however, large doses of ibuprofen increase the risk of gastrointestinal adverse effects. The use of large doses of ibuprofen in the treatment of cystic fibrosis is a relatively new therapy. Limited data thus far in cystic fibrosis patients do not suggest increased risk of gastrointestinal complications.

CONCLUSIONS:

Limited data to date indicate that ibuprofen, when used in large doses to treat the pulmonary manifestations of cystic fibrosis, is relatively safe. However, because of the potential risks to the gastrointestinal tract of high-dose ibuprofen therapy, clinicians should be aware of its possible complications.
Hydrochlorothiazide-Induced Pulmonary Edema and Associated Immunologic Changes
Authors: Bernal Carlos , Patarca Roberto
Published: March 2004

OBJECTIVE:

To describe a patient with noncardiogenic acute pulmonary edema induced by hydrochlorothiazide and to investigate the possible involvement of an immunologic mechanism in this adverse reaction.

CASE SUMMARY:

A 66-year-old Hispanic woman developed acute pulmonary edema 30 minutes after the ingestion of one tablet of triamterene 75 mg/hydrochlorothiazide 50 mg. The reaction was associated with hemoconcentration; a decreased white blood cell count with a shift to a predominance of polymorphonuclear cells; decreased serum immunoglobulin (Ig) G, IgG1, and IgG4; and increased serum IgM and complement 3 concentrations.

DISCUSSION:

Although there have been 35 reports of cases of hydrochlorothiazide-induced pulmonary edema, the etiology of this adverse reaction remains unknown. The observations presented in this case report, along with commonalities with previously reported cases, suggest that granulocytic infiltration into the lungs and IgG deposition in alveolar membranes may play a role in hydrochlorothiazide-induced pulmonary edema.

CONCLUSIONS:

Noncardiogenic pulmonary edema may be an immunologically mediated rare idiosyncratic reaction to hydrochlorothiazide.
Treatment of Obsessive-Compulsive Disorder Using Clomipramine in a Very Old Patient
Authors: Trappler Brian
Published: March 2004

OBJECTIVE:

To describe the effect of the tricyclic drug clomipramine in a very old patient with obsessive–compulsive disorder and Alzheimer dementia.

CASE SUMMARY:

A 93-year-old woman had a history of obsessive–compulsive disorder since early adulthood. The obsession consisted of remembering names of famous people and the compulsion consisted of excessive list making. With the onset of memory loss secondary to Alzheimer disease, she became increasingly anxious and compulsive as a result of a failure to remember. After nine weeks on fluoxetine she became jittery and more confused. After a two-week washout period, she was given a nine-week course of clomipramine that was carefully titrated up to a therapeutic concentration.

RESULTS:

At the completion of clomipramine treatment, the patient no longer felt driven to recall the names of famous people. Her score from the Yale–Brown Obsessive–Compulsive Scale dropped from 29 to 3. Her Folstein Mini-Mental State Examination score increased from 21 to 23.

CONCLUSIONS:

Clomipramine appeared much more effective and better tolerated than fluoxetine in this very old patient despite its potential anticholinergic effect and the coexistence of Alzheimer disease.
Contemporary Utilization of Digoxin in Patients with Atrial Fibrillation
Authors: McAlister Finlay A , Ackman Margaret L , Tsuyuki Ross T , Kimber Shane , Teo Koon K
Published: March 2004

OBJECTIVE:

To define the contemporary practice patterns of digoxin utilization for the management of patients with atrial fibrillation (AF).

METHODS:

A retrospective medical records audit of 2490 patients with documented AF, from 12 Canadian hospitals and six outpatient clinics, during fiscal year 1993–1994, was conducted.

RESULTS:

There were 1158 women and 1332 men, with a mean age of 72 years; 956 patients were <70 years of age and 1534 were ≥70 years old. The majority of patients had nonvalvular AF (75% of those with a documented etiology). Paroxysmal AF (PAF) was documented in 800 patients, 936 had chronic AF, and 754 had new-onset AF. While the prescribing patterns were heterogeneous, the predominant strategy pursued in all subgroups appeared to be that of achieving rate control. Digoxin was the most commonly prescribed medication (79%) and was prescribed for the majority of patients in all subgroups, including patients with PAF (74%) and patients with a history of chronic AF who were currently in sinus rhythm (83%). Only 10% of the patients with PAF who were prescribed digoxin had congestive heart failure. Similarly, less than 25% of the patients with chronic AF who were prescribed digoxin after conversion to sinus rhythm had evidence of heart failure.

CONCLUSIONS:

In the absence of clinical trial evidence supporting either a strategy of antiarrhythmic therapy or rate control with anticoagulation, the appropriateness of the observed prescribing practices cannot be judged. However, digoxin is not the best rate-controlling agent for all patients and may be overused in certain subgroups of patients, such as those with PAF and those successfully converted to sinus rhythm.
Compliance with Sulfonylureas in a Health Maintenance Organization: A Pharmacy Record–Based Study
Authors: Venturini Francesca , Nichol Michael B , Sung Jennifer CY , Bailey Karen L , Cody Marisue , McCombs Jeffrey S
Published: March 2004

OBJECTIVE:

To determine which factors affect compliance with sulfonylureas in a population served by a health maintenance organization in Southern California.

METHODS:

Retrospective analysis of pharmacy records and healthcare utilization data for two years (April 1993–March 1995), and a survey mailed to patients. Patients treated with sulfonylureas were selected for analysis on the basis of their prescription profile. Compliance was measured from the pharmacy records as the proportion of days the patient was in possession of the prescribed medications. Patient compliance with sulfonylureas was modeled as a function of four clusters of determinants: patient-related attributes, drug regimen characteristics and complexity, health status and disease-related variables, and characteristics of the interaction with healthcare providers.

RESULTS:

786 patients were identified for analysis (49.1% women, mean age 59 y). The mean compliance rate was 83% ± 22% SD. Compliance was significantly positively related with age and self-reported level of medication-taking compliance at baseline. Factors shown to have an inverse relationship with compliance were treatment complexity, perception of general health, and being a newly treated patient (adjusted R2 for the final model = 0.148).

CONCLUSIONS:

Our results suggest that factors found to be associated with noncompliant behavior (e.g., being a newly treated patient, self-reported compliance, regimen complexity) can be assessed by physicians and pharmacists as a routine practice.
Adverse Effects in a Newborn Infant Breast-Fed by a Mother Treated with Doxepin
Authors: Frey Otto R , Scheidt Peter , von Brenndorff Alexis I
Published: March 2004

OBJECTIVE:

To report adverse effects in a newborn infant whose mother had been treated with doxepin during pregnancy and while breast-feeding.

CASE SUMMARY:

The nine-day-old white boy was admitted because of poor sucking and swallowing, with muscle hypotonia and vomiting. He was drowsy and had lost 150 g. At the time of admission, he was breast-fed by his mother who was being treated with doxepin 35 mg/d. Samples of plasma and breast milk were taken and analyzed by HPLC and fluorescence polarization immunoassay. The amount of doxepin and N-desmethyldoxepin (DDP) ingested via breast-feeding was approximately 10–20 μg/kg/d (i.e., only 2.5% of the weight-adjusted dose of the mother). Doxepin was detectable in small amounts in the infant's plasma (∼10 μg/L); DDP was below the lower limit of detection of 10 μg/L. All adverse effects subsided within 48 hours after breast-feeding was stopped.

DISCUSSION:

Despite the small doses of doxepin and its active metabolite ingested by breast-fed babies, there is a risk of accumulation and resultant adverse effects. In newborns, the metabolic activity is considerably decreased and may be further reduced by hyperbilirubinemia.

CONCLUSIONS:

Available data suggest that women treated with doxepin should breast-feed their infants with great caution, if at all, although much larger databases are needed to confirm this.
Rhabdomyolysis Associated with Naltrexone
Authors: Zaim Sina , Wiley David B , Albano Shirley A
Published: March 2004

OBJECTIVE:

To report a possible association between naltrexone therapy and the development of rhabdomyolysis in one patient.

CASE SUMMARY:

A 28-year-old white man in good physical health was started on naltrexone 50 mg/d for inpatient treatment of alcohol dependence and depression. A routine serum chemistry panel obtained on day 9 of naltrexone therapy showed marked new elevations in creatine kinase and aspartate aminotransferase. The patient remained asymptomatic and did not develop renal insufficiency. The serum enzyme concentrations returned to normal within eight days of naltrexone discontinuation.

DISCUSSION:

Rhabdomyolysis has not been previously reported to occur in patients during treatment with naltrexone. Alcoholism may result in a reversible acute muscle syndrome, but our patient did not fit the appropriate clinical profile for such a syndrome. Additionally, the other prescribed medications could not be implicated as possible causative agents.

CONCLUSIONS:

This case report illustrates a possible association between naltrexone therapy and rhabdomyolysis.
Indirect Modulation of Dopamine D2 Receptors as Potential Pharmacotherapy for Schizophrenia: I. Adenosine Agonists
Authors: Dixon Domeeka A , Fenix Lori A , Kim Denise M , Raffa Robert B
Published: March 2004

OBJECTIVE:

To review preclinical and clinical information related to pharmacologic modulation of dopamine D2 receptors as potential novel antipsychotic therapy. Specifically, to summarize the data that suggest a modulatory action of adenosine A2A receptors on dopamine D2 receptors and, therefore, a possible rational role of adenosine A2A agonists as novel antipsychotic agents.

DATA SOURCES:

Primary and review articles were identified by MEDLINE search (from 1966 to May 1998) and through secondary sources.

STUDY SELECTION AND DATA EXTRACTION:

All of the articles identified from the data sources were evaluated and all information deemed relevant was included in this review.

DATA SYNTHESIS:

For all of the older and many of the newer antipsychotic agents, there is a strong correlation between clinical antipsychotic activity and affinity for dopamine D2 receptors. Unfortunately, dopamine D2 receptors are believed to also be involved in the adverse effect profile of these agents. The indirect modulation of dopamine D2 receptors, rather than direct block, might produce antipsychotic effects without the usual adverse reactions. Several lines of evidence from animal studies suggest that the use of selective A2A agonists might represent a novel approach to the treatment of psychoses.

CONCLUSIONS:

Dopamine receptor modulation might represent a novel antipsychotic approach or adjunct therapy. The data regarding adenosine agonists (particularly selective A2A receptor agonists) are inconclusive at the present time. Direct clinical demonstration of effectiveness is required.
Economic Impact of a Drug Information Service
Authors: Kinky Denise E , Erush Sarah C , Laskin Mitchell S , Gibson Gene A
Published: March 2004

OBJECTIVE:

A cost-avoidance model was developed to determine potential cost savings or “avoidance” that results from a drug information service (DIS) responding to drug information requests.

DESIGN:

Patient-specific questions received by the DIS were reviewed and evaluated. A panel determined whether a drug misadventure event may have occurred if the DIS had not been consulted. Potential outcomes from drug information requests were classified using a decision-tree model. A severity rating was then attached to each applicable request to predict potential cost savings of the DIS.

RESULTS:

Seventy-seven of the 570 drug information responses received in the six-week study period had assessable potential cost savings to the institution. During the study interval, potential cost savings were estimated to be $195 000. Projected to one year, potential cost savings reached $1.7 million. Of the savings noted, most were attributable to prevention of increased monitoring or additional treatment. Using a sensitivity analysis, annual potential cost savings ranged from $417 792 to $2 052 740 per year. Based on the estimated annual costs related to maintaining a DIS of $145 950, the resultant range of benefit/cost ratio is 2.9:1 to 13.2:1.

CONCLUSIONS:

This model demonstrates that the DIS at our institution provides potential cost savings. This model may be modified to evaluate potential cost savings in other areas of pharmacy practice.
Therapeutic Failure of Trimethoprim/Sulfamethoxazole in the Treatment of Pneumocystis Carinii Pneumonia
Authors: Al-Tawfiq Jaffar A , Sorensen Suellyn J , Cushing Herbert E
Published: March 2004

OBJECTIVE:

To report a case of failure of treatment of Pneumocystis carinii pneumonia (PCP) with trimethoprim/sulfamethoxazole (TMP/SMX) in a patient with HIV infection, despite an adequate serum SMX concentration.

CASE SUMMARY:

A 52-year-old white man was treated with TMP/SMX for PCP. After discharge he returned to the hospital with worsening of the PCP despite a serum SMX concentration of 60 μg/mL 18 hours after his last dose of TMP/SMX.

DISCUSSION:

PCP is one of the most common complications of HIV infection. TMP/SMX is the drug of choice for prophylaxis and treatment. The causes of therapeutic failure with this agent are not well documented.

CONCLUSIONS:

Alternative therapies to TMP/SMX should be seriously considered if the serum concentrations are therapeutic and the patient is not clinically improved.
Probable Antagonism of Warfarin by Green Tea
Authors: Taylor James R , Wilt Vickie M
Published: March 2004

OBJECTIVE:

To report a case of the inhibition of the effect of warfarin by green tea.

CASE SUMMARY:

A 44-year-old white man was receiving warfarin for thromboembolic prophylaxis secondary to a St. Jude mechanical valve replacement in the aortic position. The patient had an international normalized ratio (INR) of 3.20 approximately one month prior to entering our clinic, and an INR of 3.79 on entering our clinic. Twenty-two days later his INR was 1.37. One month later the patient's INR was 1.14. It was subsequently discovered that the patient began drinking one-half to one gallon of green tea per day about one week prior to the INR of 1.37. On discontinuation of the green tea, the patient's INR increased to 2.55.

DISCUSSION:

Warfarin produces anticoagulation by inhibiting production of the vitamin K–dependent clotting factors (i.e., factors II, VII, IX, X). The exogenous administration of vitamin K inhibits the effect of warfarin and reduces a patient's degree of anticoagulation. Green tea can be a significant source of vitamin K and thus antagonize the effect of warfarin.

CONCLUSIONS:

Warfarin is a highly effective oral anticoagulant, but it requires close monitoring to prevent complications. Patients receiving warfarin need to be routinely questioned about their intake of vitamin K–containing foods and beverages.
Significant Interactions with New Antiretrovirals and Psychotropic Drugs
Authors: Tseng Alice Lin-In , Foisy Michelle M
Published: March 2004

OBJECTIVE:

To provide an update on relevant antiretroviral interactions and psychotropic medications for healthcare practitioners managing complex HIV-related pharmacotherapy.

DATA SOURCES:

Information was retrieved via a MEDLINE search (January 1966–September 1998) using MeSH headings human immunodeficiency virus, drug interactions, psychiatry, psychotropics, psychiatric illness, and names of medications commonly prescribed for the management of HIV infection. Abstracts of international and national conferences (until February 1999), review articles, textbooks, and references of all articles also were searched.

STUDY SELECTION AND DATA EXTRACTION:

Literature on pharmacokinetic interactions was considered for inclusion. Pertinent information was selected and summarized for discussion. In the absence of specific data, pharmacokinetic and pharmacodynamic properties were considered in order to predict the likelihood of potential drug interactions.

DATA SYNTHESIS:

All protease inhibitors and nonnucleoside reverse transcriptase inhibitors are substrates of the cytochrome P450 system and possess enzyme-inhibiting and/or -inducing properties. Psychotropic medications also possess similar metabolic characteristics and may interact with antiretrovirals. Modifications in drug selection, dose, or dosing regimen may be needed to ensure adequate antiretroviral concentrations and thus minimize the risk of incomplete viral suppression and/or development of drug resistance. In the absence of specific data, consideration of metabolic characteristics may assist practitioners in predicting the likelihood of possible interactions.

RESULTS:

The incidence and implications of antiretroviral drug interactions are reviewed. Practical management strategies are also discussed. Comprehensive tables on clinically significant interactions with antiretroviral combinations and with psychiatric medications are provided.

CONCLUSIONS:

Given the increasing use of multiple-drug therapy, the potential for drug interactions is extremely high. Drug interactions may lead to undesirable outcomes including subtherapeutic drug concentrations and risk of antiretroviral resistance. Practitioners need to consider pharmacokinetic, pharmacologic, therapeutic, and adherence factors when managing interactions with complex antiretroviral therapy.
Physician Over-the-Counter Drug Prescribing Patterns: An Analysis of the National Ambulatory Medical Care Survey
Authors: Pradel Françoise G , Hartzema Abraham G , Mutran Elizabeth J , Hanson-Divers Christine
Published: March 2004

OBJECTIVE:

To describe the prevalence of physician over-the-counter (OTC) drug prescribing in relation to selected physician, patient, and drug characteristics.

DATA SOURCE AND METHODS:

Data from the 1990 National Ambulatory Medical Care Survey, a multistage probability clustered sample, were analyzed. Physician drug utilization was expressed in drug mentions defined as “the physician's entry of a pharmaceutical agent ordered or provided, by any route of administration, for prevention, diagnosis, or treatment.” Sampling weights were used to obtain unbiased national estimates. Cross tabulations of the drug prescription status (OTC or prescription [Rx]) with independent variables were performed, overall and by therapeutic class. The overall OTC/Rx ratio (0.11) was used as the cutoff point for distinguishing high- from low-level OTC drug prescribing.

RESULTS:

In 1990, 9.7% of physician drug mentions were of OTC drugs. Women between 16 and 34 years, Asian/Pacific Islanders, white Hispanics, and African-Americans experienced high OTC drug mentions (OTC/Rx ≥ 0.11). After stratification by drug therapeutic class, physicians in general practice, family practice, internal medicine, obstetrics/gynecology, and pediatrics highly mentioned OTC drugs.

CONCLUSIONS:

OTC drug prescribing by physicians is substantial, and primary care specialties, patient gender, age, and race should be considered by those interested in evaluating OTC drug utilization in the ambulatory care setting.
Phenobarbital Dosing and Pharmacokinetics in a Neonate Receiving Extracorporeal Membrane Oxygenation
Authors: Elliott Ellie SR , Buck Marcia L
Published: March 2004

OBJECTIVE:

To describe the dosing and pharmacokinetics of phenobarbital in a neonate receiving extracorporeal membrane oxygenation (ECMO).

CASE SUMMARY:

The treatment of a 2.6 kg, 38-week gestational age boy with congenital diaphragmatic hernia who developed seizures while receiving ECMO support is described. A loading dose of 20 mg/kg resulted in concentrations of 16.4 and 12.9 μg/mL at 3 and 24 hours, respectively. A maintenance dose of 5 mg/kg/d provided a peak concentration of 19.7 μg/mL and trough concentration of 16.7 μg/mL after four doses. The calculated volume of distribution was 1.2 L/kg and the estimated elimination half-life was 92 hours. Serum concentrations decreased after circuit changes unless the new circuit was redosed.

DISCUSSION:

The reported incidence of seizures in neonates while receiving ECMO support is 18%. Despite this frequency, there are no clinical reports describing anticonvulsant use in this population. This case demonstrates the use of standard phenobarbital doses to achieve low, but therapeutic, serum concentrations. Pharmacokinetic analysis revealed a volume of distribution slightly larger than expected in neonates and an elimination half-life similar to published values. Altering circulating blood volumes resulted in significant reductions in serum concentrations.

CONCLUSIONS:

Neonates on ECMO may have a larger volume of distribution than neonates not receiving ECMO and may require larger phenobarbital doses to achieve desired serum concentrations. This may result from the presence of large exogenous blood volumes for priming, as well as loss of drug during circuit changes, extraction by the circuit, or hemofiltration. Further work is needed to better define the pharmacokinetics and pharmacodynamics of phenobarbital in the neonatal ECMO population.
Venlafaxine and Bupropion Combination Therapy in a Case of Treatment-Resistant Depression
Authors: Fatemi S Hossein , Emamian Effat-S , Kist David A
Published: March 2004

OBJECTIVE:

To report the therapeutic efficacy of venlafaxine and bupropion in a patient with treatment-refractory major depression.

CASE SUMMARY:

A 21-year-old white woman with chronic and recurrent major depression presented with lack of response to several antidepressants. On examination, the patient exhibited neurovegetative signs of depression, guilt feelings, and suicidal ideation. The patient was administered venlafaxine 75 mg three times daily. The dose was titrated to 150 mg three times daily over the next month. Later bupropion was instituted up to 100 mg three times daily over a four-month period. The patient responded favorably to combination therapy and has remained free of depression for approximately 23 months.

DISCUSSION:

Venlafaxine and bupropion are antidepressant agents with unique pharmacologic profiles, each effective in the treatment of depression. Recent data indicate that combinations of selective serotonin-reuptake inhibitors and bupropion can convert partial response to full response in patients with treatment-resistant depression. We considered whether a combination of venlafaxine and bupropion would reduce the depressive symptoms of a patient who was unresponsive to various classes of psychotropic agents. Gradual administration of venlafaxine and bupropion acted synergistically to significantly reduce depressive symptoms (p < 0.002) and significantly increase social function (p < 0.002) over a period of eight months.

CONCLUSIONS:

To our knowledge this is the first report of successful combination therapy with venlafaxine and bupropion in treatment of chronic recurrent and refractory major depression.
Discontinuation Rates for Protease Inhibitor Regimens Containing Ritonavir 600 mg versus Ritonavir 400 mg Plus Saquinavir 400 mg
Authors: Rublein John C , Eron Joseph J , Butts John D , Raasch Ralph H
Published: March 2004

OBJECTIVE:

A retrospective study was performed to determine whether twice-daily ritonavir 400 mg plus twice-daily saquinavir 400 mg (ritonavir 400/saquinavir 400) was better tolerated than ritonavir 600 mg twice daily (ritonavir 600). A secondary objective was to determine whether the rate of discontinuation due to therapeutic failure differed between the two ritonavir regimens.

DESIGN:

The study was a retrospective chart review. Data collected included ritonavir dose; length of ritonavir therapy; reason for discontinuation; HIV-1 RNA prior to and at discontinuation of ritonavir therapy; CD4+ count; and antiretroviral therapy prior to, concomitant with, and initiated after ritonavir therapy.

SETTING:

Patient charts were reviewed in a university teaching hospital clinic.

PATIENTS:

Patients were identified through a search of the pharmacy database from December 18, 1995, to December 18, 1997. Patients were >18 years old, but not restricted by gender or race.

MAIN OUTCOME MEASURES:

The main outcome measures were frequency of discontinuation of ritonavir due to intolerance or due to lack of therapeutic efficacy.

RESULTS:

The search identified 116 patients, including 57 patients taking ritonavir 400/saquinavir 400 and 54 patients taking ritonavir 600. Five patients on other ritonavir regimens were excluded. Significantly fewer patients receiving ritonavir 400/saquinavir 400 (14%) discontinued ritonavir due to intolerance compared with ritonavir 600 (37%; p = 0.002). Discontinuations due to therapeutic failure were not significantly different: 8.8% for ritonavir 400/saquinavir 400 and 7.4% for ritonavir 600, despite the fact that ritonavir/saquinavir therapy followed another protease inhibitor in 41 patients (73.2%) compared with 12 patients (24.5%) for ritonavir 600 (p = 0.001).

CONCLUSIONS:

Ritonavir 400/saquinavir 400 is better tolerated than ritonavir 600.
Potential Fluconazole-Induced Carbamazepine Toxicity
Authors: Nair Dileep R , Morris Harold H
Published: March 2004

OBJECTIVE:

To report a case of carbamazepine toxicity resulting from a drug interaction with fluconazole, and to review the possible mechanisms of this interaction.

DATA SOURCES:

Medical record review.

DATA SYNTHESIS:

A 33-year-old white man with a history of mental retardation and seizures experienced stupor due to carbamazepine toxicity after fluconazole was initiated. The patient had been taking carbamazepine for several years and maintained stable therapeutic concentrations. He started fluconazole therapy after developing a rash presumably due to candidiasis. After admission to the hospital for carbamazepine toxicity, both fluconazole and carbamazepine were withheld and the patient returned to his normal baseline mental status once the carbamazepine concentration declined to a therapeutic range. Carbamazepine was restarted and the patient experienced no further adverse events. Carbamazepine is metabolized by the cytochrome P450 3A4 isoenzyme. Fluconazole is renally excreted but has been noted to inhibit CYP3A4. Fluconazole has also been noted to increase phenytoin concentrations.

CONCLUSIONS:

Fluconazole may cause carbamazepine toxicity presumably by inhibiting the cytochrome P450 3A4 isoenzyme.
Allergic-Type Reactions to Corticosteroids
Authors: Kamm Gayle L , Hagmeyer Kathleen O
Published: March 2004

OBJECTIVE:

To review reported cases of suspected allergic reactions to various corticosteroids.

DATA SOURCES:

A MEDLINE search (January 1966–December 1997) was performed to obtain case reports and review articles on allergic-type reactions to corticosteroids. Further references were obtained from these publications.

STUDY SELECTION:

Reports involving allergic or allergic-type reactions to systemic administration of corticosteroids were chosen for this review. An allergic-type reaction was defined as any reaction after administration of the drug that involved the appearance of adverse symptoms that are characteristic of unwanted immune responses. These symptoms include rash, sneezing, dyspnea, edema, bronchospasm, or death. Articles were excluded from the evaluation if they described reactions to topical, intraarticular, or ophthalmic corticosteroid administration.

DATA SYNTHESIS:

Corticosteroids are medications that are often used to treat allergic reactions. However, it appears that patients can also have allergic-type reactions to these agents. The severity of the reaction can vary from a rash to anaphylaxis or death. Both immediate and delayed reactions can occur. Allergic-type reactions are reported to occur more frequently in asthmatic and renal transplant patients than other patient populations. However, it is questionable whether all of these are true allergic responses, as there is conflicting evidence regarding the mechanism of the reaction. The most commonly implicated corticosteroids are methylprednisolone and hydrocortisone, but reactions have also occurred with others. Intradermal skin testing can help determine cross-sensitivity, although its value has not been conclusively demonstrated.

CONCLUSIONS:

Clinicians should be aware that allergic reactions to corticosteroids are possible. Worsening of symptoms may not always mean treatment failure, but may indicate an allergic reaction. High doses of corticosteroids (≥500 mg) should be given over 30–60 minutes, and patients should be observed after administration for at least the same time period. Asthmatics, renal transplant patients, and hemodynamically unstable patients may be at higher risk for adverse events. If a patient is found to be allergic to one corticosteroid, intradermal skin testing may help identify another corticosteroid that can be tolerated.
Marked Elevation of Serum Creatine Kinase Associated with Olanzapine Therapy
Authors: Marcus Esther-Lee , Vass Agnes , Zislin Joseph
Published: March 2004

OBJECTIVE:

To report a case of marked elevation of serum creatine kinase (CK) associated with olanzapine therapy.

CASE SUMMARY:

A 39-year-old white Jewish schizophrenic man treated with olanzapine developed an elevated serum CK concentration with a peak concentration of 4000 IU/L (normal <230). No other diagnostic criteria for neuroleptic malignant syndrome (NMS) were present. On discontinuation of the drug, serum CK concentrations returned to normal within eight days.

DISCUSSION:

Olanzapine, like other atypical antipsychotic drugs, may cause muscle injury with concomitant elevations of serum CK of muscle origin. We suggest that in patients treated with olanzapine, CK concentrations should be checked on initiation of therapy, within the first 48 hours, and weekly thereafter for at least one month. In addition, patients with clinical signs suggestive of NMS should be monitored more carefully. For those patients with a history of NMS, or even of isolated serum CK elevation during antipsychotic therapy, follow-up should be stricter.

CONCLUSIONS:

Marked elevation of serum CK may be a possible complication of olanzapine therapy.
Use of Nonprescription Medications by Patients with Congestive Heart Failure
Authors: Ackman Margaret L , Campbell Jeffrey B , Buzak Kimberly A , Tsuyuki Ross T , Montague Terrence J , Teo Koon K
Published: March 2004

OBJECTIVE:

To define the utilization pattern of nonprescription therapies in patients with congestive heart failure (CHF) and to compare this pattern with that of an age- and gender-matched control group without any self-reported heart conditions.

DESIGN:

Survey questionnaire completed by participants at home.

SETTING:

Ambulatory CHF clinic in a tertiary care hospital.

SUBJECTS:

Patients attending the clinic between July 1995 and May 1996 who agreed to participate. Control subjects were age- and gender-matched participants identified and approached by participating patients.

OUTCOME MEASURES:

Nonprescription therapies used at least once weekly.

RESULTS:

Completed questionnaires were received from 180 (75%) of the 239 patients who agreed to participate and from 133 controls. Mean age of responding patients was 69 years (63% men). Controls were younger, with a mean age of 64 years (63% men). The most commonly used nonprescription medication categories for both patients and controls, with no significant intergroup differences, were vitamins and minerals (59% patients, 50% controls), pain relievers (48% and 43%, respectively), herbal or health food products (38% and 38%), antacids (26% and 28%), and laxatives (24% and 21%). Significantly fewer patients than controls used cough and cold products (9% vs. 17%; p < 0.05), specifically oral decongestants (0.6% vs. 5%; p < 0.01), and more patients than controls used nutritional supplements (17% vs. 4%; p < 0.01).

CONCLUSIONS:

Overall, use of nonprescription therapies by our CHF clinic patients is similar to that of an age- and gender-matched population without a self-reported heart condition. The differences in medication use observed between patients and controls included cough and cold products that might be harmful. This likely reflects appropriate caution with which CHF patients approach nonprescription therapies.
Clozapine-Associated Neuroleptic Malignant Syndrome: Two New Cases and a Review of the Literature
Authors: Karagianis James L , Phillips Leslie C , Hogan Kevin P , LeDrew Kellie K
Published: March 2004

BACKGROUND:

Clozapine has recently been found to be associated with neuroleptic malignant syndrome (NMS). Our objective is to determine if clozapine causes NMS, if the presentation of clozapine-induced NMS differs from that of traditional agents, and which set of diagnostic criteria will most readily allow diagnosis of NMS associated with clozapine.

METHODS:

Two new cases of clozapine-associated NMS are presented, along with previously reported cases from the literature, identified by using a MEDLINE search (1966-August 1998). From all cases, concomitant medications and washout periods were examined (if available) to assess clozapine as the likely cause of NMS. Characteristics of clozapine and traditional antipsychotic-induced NMS were compared. Different diagnostic criteria for NMS were applied to the cases to determine which were more likely to diagnose the syndrome.

RESULTS:

Clozapine was deemed a highly probable cause of NMS in 14 cases, a medium probability cause in five cases, and a low probability cause in eight cases. The most commonly reported clinical features were tachycardia, mental status changes, and diaphoresis. Fever, rigidity, and elevated creatine kinase were less prominent than in NMS associated with classical neuroleptics.

CONCLUSIONS:

Clozapine appears to cause NMS, although the presentation may be different than that of traditional antipsychotics. Levenson's original and Add-Onizio's modified criteria were more likely to diagnose NMS than were other criteria. Clozapine-associated NMS may present with fewer clinical features. Limitations are the lack of detailed information provided by many of the case reports and the use of “modified” diagnostic criteria for retrospective diagnosis.
Dextromethorphan and Diabetic Neuropathy
Authors: Criner Tonya M , Perdun Carla S
Published: March 2004

OBJECTIVE:

To review the use of dextromethorphan for the treatment of painful diabetic neuropathy.

DATA SOURCES:

MEDLINE and EMBASE searches for studies using dextromethorphan to manage diabetic neuropathy were conducted from 1966 to 1999 and 1980 to 1999, respectively.

DATA SYNTHESIS:

Peripheral neuropathy is a common manifestation of diabetic patients. Many classes of medications have been investigated to treat this condition, including N-methyl- D-aspartate inhibitors. A review of studies using dextromethorphan to manage diabetic neuropathy was performed.

CONCLUSIONS:

There are insufficient safety and efficacy data to justify the use of dextromethorphan for treating painful diabetic neuropathy. Further clinical trials are needed.
Levofloxacin-Induced Bilateral Achilles Tendonitis
Authors: Lewis James R , Gums John G , Dickensheets David L
Published: March 2004

OBJECTIVE:

To report a case of possible levofloxacin-induced bilateral Achilles tendonitis.

CASE SUMMARY:

An 83-year-old white woman presented to her physician with five days of hemoptysis. She was diagnosed with right lower-lobe pneumonia based on chest X-ray, and levofloxacin 500 mg/d po for 10 days was prescribed. Three days into treatment she began having a variety of adverse effects, including severe nausea, constipation, stomach cramps, and dizziness. Signs of tendonitis began three days after treatment and peaked four days after completion of therapy. Two weeks later, she was treated by her podiatrist with an ankle immobilizer and rest. At her three-week follow-up, she had marked improvement in her pain and bruising; however, her symptoms had not completely resolved.

DISCUSSION:

Tendonitis and tendon rupture are rare adverse effects of fluoroquinolone antibiotics; there are no reports in the literature of levofloxacin-induced tendonitis. As newer fluoroquinolones become available, the postmarketing studies will become increasingly important to capture the data on rare but serious adverse effects not discovered in the premarketing trials.

CONCLUSIONS:

To our knowledge, this is the first reported case of tendonitis caused by levofloxacin reported in the literature. Reports have been made, however, to the manufacturer via postmarketing surveillance. As more people are treated with newer fluoroquinolones, the clinical incidence of tendon rupture with these agents may become clearer.
Naratriptan: An Alternative for Migraine
Authors: Dulli Douglas A
Published: March 2004

OBJECTIVE:

To critically evaluate the literature regarding naratriptan's clinical pharmacology, efficacy, safety, and indications.

DATA SOURCE:

A MEDLINE search was conducted for the period from January 1990 to June 1998. Key words used included naratriptan, triptan, serotonin agonists, migraine, and migraine therapy. In addition, pertinent references cited in articles obtained from MEDLINE and product information for triptans were reviewed.

STUDY SELECTION AND DATA EXTRACTION:

All original and review articles and abstracts pertaining to naratriptan were reviewed, as were product information extracts. Clinical trials of naratriptan were critically reviewed and compared with pertinent clinical trials of other oral triptans.

DATA SYNTHESIS:

The treatment of migraine has been dramatically improved with the use of sumatriptan, other triptans, and serotonin-receptor subtype 1B and 1D agonists. Drawbacks to these medications, however, have included poorly tolerated adverse effects and the recurrence of the migraine. Naratriptan has been recently approved for acute oral migraine therapy. In two Phase III trials of naratriptan compared with placebo, relief at four hours was obtained in 60% and 68% of patients using the 2.5-mg dose, with recurrence of headache in 24 hours in 27% and 28% of patients. The data on migraine recurrence were similar to those of other oral triptans; the efficacy of naratriptan at two hours was not specifically analyzed. Adverse effects of naratriptan were similar to placebo, and its tolerability seemed superior compared with studies of other oral triptans.

CONCLUSIONS:

Naratriptan is a promising new oral therapy for acute migraine; it may successfully treat patients who poorly tolerate other triptan therapies or have longer duration migraine headaches.
Acute Renal Failure after Large Doses of Intravenous Immune Globulin
Authors: Haskin Janet A , Warner David J , Blank Douglas U
Published: March 2004

OBJECTIVE:

To describe a case of acute renal failure after high-dose intravenous immune globulin (IVIG) therapy and the measures undertaken to prevent this complication during subsequent administration.

CASE SUMMARY:

A 54-year-old white man with valvular cardiomyopathy was receiving large doses (2 g/kg/mo) of IVIG in order to attenuate his immune system in preparation for a heart transplant. After his first infusion, he had to be rehospitalized for nausea, vomiting, fever, chills, and acute renal failure (serum creatinine [Scr] peak 8.4 mg/dL, baseline 1.0 mg/dL). His second infusion produced similar complications. Sandoglobulin 100 mL/h (172 g; 10% solution prepared with sterile water) was used on both occasions, and the large sucrose load (1.67 g sucrose/g protein) was suspected to be the causative agent. Upon switching to Polygam (170 g; 10% solution prepared with sterile water), a glucose-containing product which only has 0.4 g glucose/g protein, and infusing it at half of the Sandoglobulin rate (50 mL/h), the patient was able to tolerate the infusion without complications (Scr and blood urea nitrogen unchanged).

DISCUSSION:

Stabilizing agents such as sucrose, maltose, and glucose are added to IVIG preparations to help reduce immunoglobulin aggregation. These aggregates are associated with some of the more serious adverse effects of IVIG administration. When large doses of IVIG are used, the stabilizing agents can induce an osmotic nephrosis due to the large solute load. A review of the previous literature on IVIG-induced renal failure is provided, as well as the differences in the various IVIG formulations. Also, general guidelines are offered to prevent this complication.

CONCLUSIONS:

Large doses of Sandoglobulin (400–2000 mg/kg) have been associated with acute renal failure due to the large sucrose load. By taking certain precautions, especially in high-risk patients, this uncommon, but serious, adverse effect can be avoided.
Onycholysis Associated with Weekly Administration of Paclitaxel
Authors: Flory Stefanie M , Solimando Dominic A , Webster Guy F , Dunton Charles J , Neufeld Julia M , Haffey Mary B
Published: March 2004

OBJECTIVE:

To report an unusual reaction associated with weekly administration of paclitaxel.

CASE SUMMARIES:

Onycholysis was seen in four women with recurrent ovarian cancer being treated with low-dose, weekly paclitaxel. Two of the patients had previously received higher doses of paclitaxel on an every-three-week schedule without similar reactions. Onycholysis developed between weeks 10–13 of treatment in three of the patients. In the fourth patient, it developed shortly after initiation of weekly paclitaxel. None of the reactions required dose adjustments or discontinuation of therapy. Direct toxicity to the nail bed or inhibition of angiogenesis are possible mechanisms for this reaction.

DISCUSSION:

Onycholysis, separation of the nail from the nail bed, is an infrequent adverse effect of drug therapy. Antineoplastic drugs have previously been reported to cause onycholysis, pigmentation, bands, thickening or thinning of the nail bed, and nail shedding. Nail changes with the taxanes, primarily docetaxel, are reported in up to 30–40% of patients. Paclitaxel is not commonly associated with dermatologic reactions, although localized skin reactions and tissue necrosis have been reported. Nail changes, pigmentation or discoloration of the nail bed, occur in 2% of patients receiving paclitaxel.

CONCLUSIONS:

Onycholysis is an uncommon reaction that may occur in some patients receiving weekly, low-dose paclitaxel therapy. The reaction is not life-threatening and does not warrant discontinuation of therapy. However, clinicians should be aware of the possibility of this effect and be prepared to advise patients who develop signs of nail changes.
Effect of Over-the-Counter Cimetidine on Phenytoin Concentrations in Patients with Seizures
Authors: Rafi John A , Frazier Lisa M , Driscoll-Bannister Susan M , O'Hara Kathryn A , Garnett William R , Pugh Carol B
Published: March 2004

OBJECTIVE:

To determine the effects of the maximum recommended over-the-counter (OTC) cimetidine dosage on phenytoin concentrations in ambulatory seizure patients on long-term phenytoin therapy.

METHODS:

Adults with seizure disorders requiring phenytoin therapy were recruited. Trough total phenytoin concentrations were measured initially and once weekly for six weeks. All assays were performed using Biotrack patient-side cartridges. After a two-week baseline period, patients took cimetidine 200 mg twice daily for two weeks. Toxicity was monitored via weekly neurologic examinations and midweek telephone surveys. Patients were asked to return to clinic weekly during a two-week cimetidine washout period.

RESULTS:

Nine patients entered and completed the study. All but two patients took other anticonvulsants known to interact with phenytoin (carbamazepine, n = 5; phenobarbital, n = 2). No adverse effects or changes in seizure frequency were reported. Paired Student's t-tests revealed no significant difference between serum phenytoin concentrations before (12.3 ± 3.2 mg/L [mean ± SD]) and after (12.8 ± 4.0 mg/L) two weeks on the OTC cimetidine regimen. No differences were noted in estimated pharmacokinetic parameters (maximum metabolic rate, Michaelis–Menten constant) for the same time periods (paired Student's t-test, p > 0.05). The Biotrack assay had an r2 = 0.7311 (p < 0.001, two-sided) when compared with TDx.

CONCLUSIONS:

It is possible that the lack of change in phenytoin concentrations was a result of the low daily dosage of cimetidine used or other factors related to the “real world” setting of the study. However, the potential for a serious drug interaction occurring in patients taking long-term oral phenytoin and OTC cimetidine appears to be small.