Showing papers by "American Pharmacists Association published in 2001"

Practical approach to determining costs and frequency of adverse drug events in a health care network.

Abstract: The frequency, preventability, severity, root causes, and projected costs of adverse drug events (ADEs) occurring after or causing admission to a four-hospital integrated academic health network were studied. The sample included all admissions during a 53-day study period. Events were identified through daily record review of a random patient sample, computerized flags, and self-reporting. A case review committee validated the occurrence, classification, and root causes of the events. Additional length of stay and costs associated with ADEs were analyzed by using a case-control, multiple linear regression model. The estimated ADE rate during hospitalization was 4.2 events per 100 admissions, with a cost of $2162 per ADE. In addition, 3.2% of admissions were caused by ADEs, with an associated cost of $6685 per event. Fifteen percent of hospital ADEs and 76% of ADEs causing admission were judged preventable. The annual cost to the organization for events occurring during hospitalization was $1.7 million, and the cost of preventable ADEs was $260,000, while the projected costs of preventable ADEs causing admission were $3.8 million. The rate of admissions to the mental health center caused by ADEs was higher than for other settings at 13.6%, with a cost of preventable ADEs of $1.3 million. Patient noncompliance was judged to be the cause of the 69% of the ADEs causing admission. Seventy-one percent of the serious medication errors occurred at the prescribing stage of the medication-use process. ADEs were frequent, costly, and often preventable and resulted in many admissions to a mental health center.

Antipsychotic polypharmacy: a survey of discharge prescriptions from a tertiary care psychiatric institution.

Abstract: Objective:To perform a retrospective survey of discharge medications at a tertiary care psychiatric facility and to assess the incidence of antipsychotic polypharmacy.Method:This is a retrospective survey that used the Department of Pharmacy's computer database to obtain relevant discharge information on all nongeriatric patients with schizophrenia discharged from Riverview Hospital between November 1, 1996 and October 31, 1998. From a total of 492 eligible patients, 229 met the inclusion criteria and formed the database for the survey.Results:The main finding of the survey was that 27.5% of our discharged patients diagnosed with schizophrenia left our facility on an antipsychotic polypharmacy regimen. Compared with patients discharged on a single antipsychotic, the pooled data revealed a significantly greater use of anticholinergic agents in those patients prescribed an antipsychotic polypharmacy regimen. Further, of the atypical agents, only risperidone showed a statistically significant reduction in do...

Perioperative activation of hemostasis in vascular surgery patients

Abstract: BackgroundPerioperative activation of hemostasis could play an important role in the occurrence of postoperative cardiac events. The authors conducted a prospective study to assess platelet function, coagulation, and fibrinolysis status during and after infrarenal aortic surgery.MethodsSeventeen pat

Management of Childhood Acute Respiratory Infections at Private Pharmacies in Vietnam

Abstract: OBJECTIVE:To investigate the knowledge and practice among private pharmacy staff in Hanoi regarding case management of mild acute respiratory infection (ARI) in children.METHODS:Sixty private pharmacies in Hanoi were randomly selected. Knowledge was assessed through interviews with pharmacy staff using a questionnaire; practice was assessed through the Simulated Client Method.RESULTS:In the questionnaire, 20% of the pharmacy staff stated that they would dispense antibiotics. In practice, 83% of the pharmacies dispensed antibiotics. Only 36% of the cases were handled according to guidelines. In the questionnaire, 81% of interviewees stated that antibiotics are not effective in short therapeutic courses. In practice, 48% of the antibiotics were dispensed in courses less than five days. Traditional herbal medicines were dispensed in 41% of the encounters. In the questionnaire, 53% of the pharmacy staff stated that they would ask the patient about difficulty of breathing. In practice, questions related to dif...

The transfer half-life of morphine-6-glucuronide from plasma to effect site assessed by Pupil size measurement in healthy volunteers

Abstract: Background: Clinical and experimental data suggested a long delay between the plasma concentration versus time course of morphine-6-glucuronide and the time course of its central opioid effects. This study was aimed at the quantification of the transfer half-life (t 1/2,ke0 ) of this delay. Methods: Pupil size was used as a measure of central opioid effect. Eight healthy volunteers (four men, four women) participated in that single-blind randomized crossover study. Median dosages administered intravenously were 0.5 mg morphine as loading dose followed by 10.7 mg given as infusion over a period of 4.7 h, and 10.2 mg M6G as loading dose followed by 39.1 mg M6G given over a period of 3.7 h. The duration of the infusion was tailored to achieve submaximum pupil constriction. The pupil diameter was assessed every 20 min for approximately 18 h. Values of t 1/2,ke0 were obtained by semiparametric pharmacokinetic-pharmacodynamic modeling. Results: The estimated median t 1/2,ke0 of M6G was 6.4 h (range, 2.9-16.2 h), and that of morphine was 2.8 h (range, 1.8-4.4 h). The individual t 1/2,ke0 of M6G was always longer than that of morphine. Judged by the concentration at half-maximun effect (EC 50 ) values of the sigmoid pupil size at maximum constriction (E max ) model describing concentration-response relation, M6G was apparently 22 times less potent than morphine (EC 50 = 740.5 nM [range, 500-1,520 nM] for M6G and 36.2 nM [range, 19.7-43.3 nM] for morphine). The steepness of the sigmoid E max model did not significantly differ between morphine and M6G (y = 1.9 and 2.6, respectively). To produce similar pupil effects, the M6G dose had to be 2.8 times greater than the morphine dose. Conclusions: The reported numerical value of the t 1/2,ke0 of M6G in humans obtained after direct administration of M6G is a step toward a complete modeling approach to the prediction of the clinical effects of morphine. The study raises questions about the high interindividual variability of the transfer half-life between plasma and effect site (k e0 ) values and the apparent low potency of M6G.

The transfer half-life of morphine-6-glucuronide from plasma to effect site assessed by pupil size measurement in healthy volunteers.

Abstract: Background: Clinical and experimental data suggested a long delay between the plasma concentration versus time course of morphine-6-glucuronide and the time course of its central opioid effects. This study was aimed at the quantification of the transfer half-life (t 1/2,ke0 ) of this delay. Methods: Pupil size was used as a measure of central opioid effect. Eight healthy volunteers (four men, four women) participated in that single-blind randomized crossover study. Median dosages administered intravenously were 0.5 mg morphine as loading dose followed by 10.7 mg given as infusion over a period of 4.7 h, and 10.2 mg M6G as loading dose followed by 39.1 mg M6G given over a period of 3.7 h. The duration of the infusion was tailored to achieve submaximum pupil constriction. The pupil diameter was assessed every 20 min for approximately 18 h. Values of t 1/2,ke0 were obtained by semiparametric pharmacokinetic-pharmacodynamic modeling. Results: The estimated median t 1/2,ke0 of M6G was 6.4 h (range, 2.9-16.2 h), and that of morphine was 2.8 h (range, 1.8-4.4 h). The individual t 1/2,ke0 of M6G was always longer than that of morphine. Judged by the concentration at half-maximun effect (EC 50 ) values of the sigmoid pupil size at maximum constriction (E max ) model describing concentration-response relation, M6G was apparently 22 times less potent than morphine (EC 50 = 740.5 nM [range, 500-1,520 nM] for M6G and 36.2 nM [range, 19.7-43.3 nM] for morphine). The steepness of the sigmoid E max model did not significantly differ between morphine and M6G (y = 1.9 and 2.6, respectively). To produce similar pupil effects, the M6G dose had to be 2.8 times greater than the morphine dose. Conclusions: The reported numerical value of the t 1/2,ke0 of M6G in humans obtained after direct administration of M6G is a step toward a complete modeling approach to the prediction of the clinical effects of morphine. The study raises questions about the high interindividual variability of the transfer half-life between plasma and effect site (k e0 ) values and the apparent low potency of M6G.

Nonprescription Drug—Related Problems and Pharmacy Interventions

Abstract: OBJECTIVE:To document the number and types of drug-related problems (DRPs) identified in customers purchasing nonprescription products in Swedish pharmacies; describe the distribution of DRPs by customer's gender, age, underlying ailment, and class of drug; determine whether problems are identified to the same extent in pharmacies with staffed nonprescription self-service departments as in pharmacies with over-the-counter sales; and document the number and types of pharmacy interventions to prevent or resolve DRPs, including reasons for drug switches and referrals to physicians.METHODS:A computerized instrument for documentation of DRPs and pharmacy interventions was developed. The study was conducted in 45 volunteer pharmacies in Sweden during 10 weeks in late 1999.RESULTS:A total of 1425 problems and 2040 interventions were recorded by 308 pharmacy practitioners. Relatively fewer DRPs were documented in pharmacies with self-service departments. The most common DRPs were uncertainty about the indication ...

Pulmonary Fibrosis Induced by Cyclophosphamide

Abstract: OBJECTIVE:To report a case of pulmonary fibrosis resulting from use of cyclophosphamide as chemotherapy to treat a patient with breast cancer.CASE SUMMARY:We describe the case of a 52-year-old woman with breast cancer who developed pulmonary fibrosis after four cycles of chemotherapy that included cyclophosphamide. Pulmonary function tests revealed the presence of a severe ventilatory restriction. The open lung biopsy revealed pulmonary fibrosis with vascular sclerosis and signs of pulmonary hypertension.DISCUSSION:Cyclophosphamide is an alkylating agent that has been associated with interstitial pneumonia and pulmonary fibrosis. The frequency of these unwanted effects is '1%. The clinical picture consists of the progressive appearance of dyspnea and a nonproductive cough that progresses to severe pulmonary insufficiency. The risk factors described for these complications have been the use of chemotherapy regimens that include other drugs with known pulmonary toxicities, the cumulative total dose, the add...

Hypersensitivity Related to Abacavir in Two Members of a Family

Abstract: TO THE EDITOR: The principal adverse effect of abacavir, a potent reverse transcriptase inhibitor, is a hypersensitivity reaction, which is seen in approximately 5% of patients, usually within the first six weeks of therapy.1 This is characterized by fever, nausea/vomiting, malaise, and/or rash, and respiratory symptoms.2,3 We report cases occurring in a father and his daughter. Case Reports. A 39-year-old white HIV-infected man with no known drug allergy received zidovudine, lamivudine, saquinavir, and cotrimoxazole for several years. His CD4+ count was 180/mm3 and plasma HIV-1-RNA 16 000 copies/mL. Fifteen days after abacavir 300 mg twice daily was added to the preexisting treatment regimen, the patient developed nausea, vomiting, and fever. Three days later, he was admitted to the hospital with high fever and a circulatory collapse (BP 70/40 mm Hg). Other complications included headache, diarrhea, generalized erythema, neutropenia (441 cells/mm3), cytolytic hepatitis, and increase in serum creatinine concentration (169 μmol/L) and C-reactive protein (18.8 mg/L). All treatments were stopped. The duration of abacavir therapy was 17 days. Within seven days, the clinical and biological status of the patient improved. The eosinophil count had always been normal. When the patient was discharged, co-trimoxazole, saquinavir, nelfinavir, zidovudine, and lamivudine were resumed with no adverse event. For years, the patient had complained of chronic rhinitis: in this context, total immunoglobulin (Ig) was within the normal range. The daughter of this patient, a nine-year-old girl (140 cm/35 kg), without known atopy or drug allergy, had been treated for mother-to-child HIV transmission since she was 18 months old. She had been treated with lamivudine and efavirenz for several months. Nine days after the start of abacavir 300 mg twice daily, she developed headache, fatigue, and fever (39 ̊C). In the following days, the fever increased, and erythema of the face, trunk, and limbs appeared. Abacavir was discontinued, and all symptoms resolved within one day without treatment. Biological tests were not performed. Her new treatment regimen comprises efavirenz, stavudine, and lamivudine. Use of the Naranjo ADR probability scale4 indicated a possible relationship between adverse effects reported and abacavir in these patients. Discussion. Abacavir-related hypersensitivity reaction may limit the use of this drug in a small number of patients. The management of this adverse effect is now well documented, and rechallenge with abacavir is unnecessary.5 This is the first report of a familial hypersensitivity reaction to abacavir. The genetic predisposition of drug allergy is known with antibiotics: children of parents who are allergic to an antibiotic have been reported6 to have a 15-fold greater relative risk for allergic reactions to antibiotics than children without such family histories. Hypersensitivity reactions to drugs can be explained by immunologic and/or metabolic pathways involving cytochrome P450. Abacavir is not metabolized by cytochrome P450, and the reactivity of the formed metabolites is unknown. Immunologic factors may also be involved. In cases previously reported,2,3 the rapid onset of hypotension after rechallenge with abacavir may point to an IgE-mediated reaction, although there is no direct evidence of this type of reaction. A recent study7 suggests that epidermal cytokines and activated CD8+ lymphocytes are involved in abacavir-induced hypersensitivity. All infiltrating lymphocytes expressed HLA-DR, with no evidence of B cells, eosinophils, or CD23 expression (suggesting the absence of type 2 cytokines such as interleukin 4). The conclusions of this study suggest that the immune response in the skin does not involve antibody responses and type 2 cytokines, but may be primarily a type 1 cytokine response. The absence of CD4+ cells in the epidermis distinguishes this rash from more severe cutaneous adverse events, such as Stevens–Johnson syndrome. At this time, the pathogenesis (metabolic, immunologic, or genetic) of this reaction is undefined. Thus, our cases suggest that the genetic predisposition may play a role in abacavir hypersensitivity. The research of the precise mechanisms underlying this hypersensitivity reaction should allow to propose predictive factors to this reaction and to improve the risk/benefit ratio of this essential drug. Although confirmation is needed, abacavir should be administered with caution in children of parents who have developed a hypersensitivity reaction.

Phenytoin and Fluorouracil Interaction

Abstract: OBJECTIVE:To report a probable drug interaction between phenytoin and fluorouracil.CASE REPORT:A 66-year-old white man started adjuvant chemotherapy for colon cancer with weekly bolus injections of fluorouracil and leucovorin calcium. He had been taking phenytoin 300 mg/d for epilepsy for more than four years. Eleven weeks later, the patient was reported to be unsteady on his feet and had fallen several times. The serum phenytoin concentration at that time was 36 μg/mL. The phenytoin dosage was decreased and the symptoms resolved. Phenytoin concentrations were monitored and the dosages were adjusted accordingly throughout the remaining 15 weeks of treatment with fluorouracil. After completion of chemotherapy, the phenytoin dose was gradually increased to the original dose with no signs of toxicity.DISCUSSION:Phenytoin is principally metabolized by CYP2C9. Inhibition of that isoenzyme by fluorouracil, and possible interference with its synthesis, appears to be the most likely cause of this interaction. The...

Cerivastatin and Gemfibrozil—Associated Rhabdomyolysis

Abstract: OBJECTIVE:To report a case of rhabdomyolysis resulting from concurrent use of cerivastatin and gemfibrozil.CASE SUMMARY:An 82-year-old white man presented to the emergency department with severe muscle weakness and inability to walk approximately one month after starting cerivastatin. He had been taking gemfibrozil for several years without any known adverse effects. Both medications were discontinued and the patient recovered. He was discharged with a diagnosis of rhabdomyolysis secondary to his medications.DISCUSSION:Four previous reports describing rhabdomyolysis in patients on concomitant cerivastatin and gemfibrozil have been cited. Although monotherapy with cerivastatin is well tolerated and has a low frequency of adverse events, the combination with nicotinic acid (i.e., niacin) or a fibric-acid derivative (i.e., gemfibrozil, fenofibrate) may result in severe skeletal muscle toxicity and rhabdomyolysis.CONCLUSIONS:According to the Naranjo scale, a probable relationship exists between the concomitan...

What's ahead in glucose monitoring? New techniques hold promise for improved ease and accuracy.

Abstract: Advances in blood glucose monitoring have made it easier, more comfortable, and more practical for patients to monitor frequently. The new meters for intermittent monitoring are smaller and less dependent on technical aptitude than older models. They require less blood, and many provide downloadable information for glucose analysis. Data systems used with new meters provide valuable information that can dramatically improve glycemic control. Continuous glucose sensing (figure 4) is another major breakthrough in management of diabetes. Current systems allow only retrospective analyses, but real-time readings should be available in the near future. Such technological advances hold promise for preventing both hypoglycemia and hyperglycemia and for reducing the risk of long-term complications associated with diabetes. An artificial, mechanical islet cell may be the big next step toward bringing this disease under control. By combining continuous glucose monitoring data with continuous insulin delivery via an external or an implantable insulin pump, the outlook promises to be much brighter for patients with type 1 diabetes.

Coenzyme Q10: A Review:

Abstract: Coenzyme Q10 (CoQ10) is a provitamin manufactured by the body. It functions as a coenzyme for mitochondrial enzymes. It has been shown to be deficient in patients with cardiovascular disease, cance...

Anticoagulation Therapy for Radiation-Induced Myelopathy

Abstract: OBJECTIVE:To report the use of heparin and enoxaparin for radiation-induced myelopathy.CASE SUMMARY:A 46-year-old white woman with presumed metastatic lung cancer presented with worsening numbness and weakness of both legs. The neurooncology service was consulted and determined that the symptoms were consistent with radiation-induced myelopathy. The patient briefly responded to steroid treatment. A trial of intravenous heparin therapy was initiated by the primary team and managed by the clinical pharmacy services. Her symptoms improved when heparin was begun. She was able to walk and was subsequently discharged home on enoxaparin.DISCUSSION:Spinal cord injury is one of the known adverse effects of radiation. The onset of symptoms can be acute or delayed. The clinical signs and symptoms of delayed neurologic injury are related to the narrowing and occlusion of the vessel lumen, ischemia, edema, and cell death in the surrounding nervous tissue. Treatment often consists of corticosteroids and/or hyperbaric o...

Converting Patients from Brand-Name Clozapine to Generic Clozapine

Abstract: OBJECTIVE:To evaluate safety and dosage requirements when patients taking brand-name clozapine (Clozaril, Novartis Pharmaceuticals) are converted to generic clozapine (Zenith Goldline).METHODS:In November 1999, patients at Colorado Mental Health Institute at Pueblo taking Clozaril were changed to generic clozapine. Seventeen patients had been prescribed Clozaril for three years and were included in the study. Drug dosage, white blood cell (WBC) count values, and adverse drug reaction reports were compared. Data regarding patients on the brand-name product were evaluated retrospectively for the months of November, December, January, and February during the years 1996/1997, 1997/1998, and 1998/1999. These data were compared with those from the same patients after switching to generic clozapine for the same months in 1999/2000. A one-year comparison of brand-name (1998/1999) with generic drug (1999/2000) was also performed. Statistical analysis included a standard t-test comparing WBC values and a Brown—Fors...

Seizures with Intravenous Codeine Phosphate

Abstract: OBJECTIVE:To describe an adverse effect with intravenous codeine in a child diagnosed with sickle cell anemia.CASE SUMMARY:A seven-year-old boy with sickle cell anemia was admitted to the emergency department with severe pain unresponsive to high doses of oral acetaminophen; subsequently, intravenous codeine phosphate was administered. The patient immediately developed a tonic—clonic seizure, which was treated with intravenous diazepam and naloxone.DISCUSSION:Seizures associated with the intravenous administration of codeine phosphate have not been extensively reported in the literature, and special precautions for using the parenteral route for this drug have been vague and limited. Because of the frequent need for acute pain control in children with sickle cell crisis, they may be exposed to this type of reaction when intravenous narcotics are administered. The need for clear guidelines regarding the drug's appropriate parenteral dosing and administration is essential.CONCLUSIONS:Codeine phosphate—induc...

Seizure Induced by Ropivacaine

Abstract: OBJECTIVE:To report development of a seizure after administration of ropivacaine.CASE SUMMARY:A 26-year-old woman was scheduled for a cesarean section because of a stagnation of the uterine neck dilatation after 4.5 hours. After peridural administration of 279 mg of ropivacaine (total dose) over five hours, she presented with oculogyric movements and slurred speech that preceded convulsions of the face and of the upper limbs.DISCUSSION:Convulsions are well-known complications of local anesthetics. Ropivacaine, a relatively new agent, is considered safer for the central nervous system. Currently, there are only four published reports that implicate ropivacaine as being associated with convulsions. The likelihood that ropivacaine caused the seizure in our patient was possible based on the Naranjo probability scale.CONCLUSIONS:Clinicians should be aware of the possibility of seizures as an adverse effect of ropivacaine.

Intravenous clonidine use in a neonate experiencing opioid-induced myoclonus.

Abstract: USE of clonidine in the management of pain and opioid taper is well-established for adults. Various treatment modalities have been described, ranging from abrupt opioid cessation with clonidine substitution to gradual taper with clonidine as an adjunct. Oral administration of clonidine in neonatal abstinence syndrome has been cited as safe and effective. Short-term use of intravenous clonidine for sedation in children has been recently reported in the literature. This report describes prolonged and continuous use of intravenous clonidine in the management of opioid-induced myoclonus and opioid taper in a neonate.

Lamotrigine: a review of clinical studies in bipolar disorders.

Abstract: Objectif : Cet article examine les etudes publiees sur l'utilisation de la lamotrigine dans le traitement du trouble bipolaire (TB). Methode : Nous avons effectue une recherche dans Medline afin de reperer les bases de donnees disponibles sur les essais ouverts, les essais a double insu et les series de cas portant sur l'utilisation de la lamotrigine pour traiter le TB. Resultats : Trois essais a double insu, 3 essais ouverts et 2 series de cas ont ete menes jusqu'ici (n = 401 patients). La plupart des patients ne repondaient pas ou repondaient partiellement aux autres regulateurs de l'humeur. En tout, 50% a 83% des patients repondaient a la lamotrigine, les doses des etudes variaient de 50 a 400 mg par jour. Avec une dose de 200 mg de lamotrigine, le passage a la manie etait extrement rare, et aucun effet indesirable grave n'a ete declare durant la periode des etudes. Conclusion : La lamotrigine se revele un agent efficace dans le traitement du TB et peut etre utile aux patients qui n'ont pas repondu aux autres regulateurs de l'humeur.

Aseptic Meningitis Related to Valacyclovir

Abstract: both digoxin and drugs known to effect digoxin absorption (such as liquid antacids and antidiarrheals) on a long-term basis, it is recommended to separate their times of administration by at least two hours. 8 We chose to separate the dosing times of digoxin and cisapride in our patient by four hours because it was a practical approach for our patient to adhere to, as we aimed to reduce the promotility effect of cisapride on digoxin absorption. An improvement in both clinical response and digoxin concentration appeared to be achieved by this approach. We recommend that physicians remain vigilant to any potential interaction between cisapride and digoxin.

Practice Guidelines for Lipid-Based Amphotericin B in Stem Cell Transplant Recipients:

Abstract: OBJECTIVE:To provide clinicians who practice in the stem cell transplantation (SCT) setting with practical guidelines for the use of lipid-based amphotericin B (AmB) formulations in SCT patients who have documented or probable invasive fungal infections, are experiencing neutropenic fever, or require secondary prophylaxis for fungal infections.DATA SOURCES:Recommendations are based on the results of a two-day consensus meeting that convened clinicians versed in the management of infectious complications in patients undergoing SCT. This meeting, which was held October 21–23, 1998, in Orlando, Florida, was sponsored by an educational grant from The Liposome Company. In addition, primary articles were identified by MEDLINE search (1980–December 1999) 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:Immunocompromised patients, particularly patient...

Training and support program for pharmacists in rural Victoria.

Abstract: The ‘Rural Pharmacist Training and Support Program’ was a pilot project that was conducted by the Monash University Centre for Rural Health. It examined the implementation of Pharmacy Board of Victoria Guidelines to Residential Care Facilities in the Loddon Mallee region of Victoria. Through a series of workshops, pharmacists were encouraged to discuss and address difficulties that were impeding implementation of the guidelines. These included upskilling in clinical pharmacy and ways to overcome the shortage of pharmacists in rural areas. Furthermore, the project was a catalyst for eight additional outcomes. This project highlighted the challenges facing rural pharmacists as they seek to implement the guidelines and resulted in a number of recommendations that addressed workforce issues, training and continuing education, Pharmacy Board requirements, improved communication with other health professionals and undergraduate training.

Bromide Intoxication and Pseudohyperchloremia

Abstract: 1. Hirsh J, Dalen JE, Anderson DR, Poller L, Bussey H, Ansell J, et al. Oral anticoagulants. Mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 1998;114(suppl):445S-69S. 2. Cropp JS, Bussey HI. A review of enzyme induction of warfarin metabolism with recommendations for patient management. Pharmacotherapy 1997;17:917-28. 3. Michalets EL. Update: clinically significant cytochrome P-450 drug interactions. Pharmacotherapy 1998;18:84-112. 4. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45. 5. Miller LG. Recent developments in the study of the effects of cigarette smoking on clinical pharmacokinetics and clinical pharmacodynamics. Clin Pharmacokinet 1989;17:90-108. 6. Miller LG. Cigarettes and drug therapy: pharmacokinetic and pharmacodynamic considerations. Clin Pharm 1990;9:125-35. 7. Schein JR. Cigarette smoking and clinically significant drug interactions. Ann Pharmacother 1995;29:1139-48. 8. Zevin S, Benowitz NL. Drug interactions with tobacco smoking: an update. Clin Pharmacokinet 1999;30:425-38. 9. Mungall DR, Luden TM, Marshall J, Hawkins DW, Talbert RL, Crawford MH. Population pharmacokinetics of racemic warfarin in adult patients. J Pharmacokinet Biopharm 1985;13:213-27. 10. Bachmann K, Shapiro R, Fulton R, Carroll FT, Sullivan TJ. Smoking and warfarin disposition. Clin Pharmacol Ther 1979;25:309-15. 11. Weiner B, Faraci PA, Fayad R, Swanson L. Warfarin dosage following prosthetic valve replacement: effect of smoking history. Drug Intell Clin Pharm 1984;18:904-6. 12. Ahmad S. Lovastatin–warfarin interaction (letter). Arch Intern Med 1990;150:2407. 13. Grau E. Simvastatin–oral anticoagulant interaction (letter). Lancet 1996; 347:405-6. 14. Trilli LE, Kelley CL, Aspinall SL, Kroner BA. Potential interaction between warfarin and fluvastatin. Ann Pharmacother 1996;30:1399-402. 15. Hobbs WR, Rall TW, Verdoorn TA. Hypnotics and sedatives: ethanol. In: Hardman JG, Limbird LE, editors-in-chief, Goodman & Gilman’s the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill, 1996:387-92.

Warfarin and Ropinirole Interaction

Abstract: OBJECTIVE:To report a case of increased international normalized ratio (INR) in a geriatric patient receiving warfarin and ropinirole.CASE SUMMARY:A 63-year-old African-American man with a history of Parkinson disease, Alzheimer disease, and status postcardio-vascular accident was evaluated for symptoms of progressing stiffness and rigidity. Ropinirole was added to his current therapy for Parkinson disease, with a corresponding decrease in the dose of levodopa/carbidopa to allow levodopa sparing. On laboratory evaluation, he was noted to have an increased INR nine days after these adjustments; the INR had previously been stable. No other significant medication, social, or diet changes were noted. Warfarin was withheld for four days and restarted at approximately 75% of the previous weekly dose. The patient had no obvious signs of bleeding. Furthermore, the warfarin dose was again increased after discontinuation of ropinirole due to common gastrointestinal adverse effects.DISCUSSION:Warfarin is an oral ant...

Systemic Adverse Effects from Topical Doxepin Cream

Abstract: TO THE EDITOR:We report a case of anticholinergic toxicity associated with topically applied doxepin in an elderly man. Case Report. An 80-year-old white male nursing home patient with moderately severe dementia was treated for several months for excoriations on both arms from frequent scratching. No skin rash was evident. Initially, the areas were kept clean and covered with a dressing; however, the scratching continued. Over several months, attempts at management included long-sleeve shirts, gloves, taped arm wraps, and nonmedicated moisturizing lotions. The scratching and excoriations persisted. Considering the scratching as a neurodermatitis and perhaps a manifestation of the patient’s dementia, empiric treatment was begun with haloperidol 1 mg at bedtime. This was discontinued after a two-week trial without benefit. He was then started on carbamazepine 100 mg twice daily, and the dosage was increased to 100 mg in the morning and 200 mg at bedtime after one week. No benefit was seen after three weeks of treatment; therefore, the carbamazepine was discontinued. Additionally, as empiric treatment for possible atopic dermatitis, hydroxyzine 25 mg twice daily for two weeks and loratadine 10 mg/d for five weeks were given in separate trials. The antihistamine therapy produced no changes in the scratching behavior. A trial of acetaminophen was initiated and continued through the time of doxepin therapy; this agent was also ineffective. Therapy with doxepin 5% topical cream was initiated, which was applied to both arms as well as areas on his legs and back three times daily. After two days, the nurses noted the patient was more confused and was yelling. On the third day, he began having difficulty voiding and over the next several days required frequent catheterizations. He also became “thick-tongued.” On day 6 of doxepin therapy, he required treatment for a stool impaction. On day 14 of treatment, the patient began having visual hallucinations, reaching for objects in the air. Doxepin was discontinued at that time. Most of a 30-g tube of doxepin cream had been used. Over the next few days, the patient voided more easily without the need for catheterizations. One week later, the yelling and hallucinations decreased significantly, but persisted. He continued to exhibit some increased confusion compared with that before doxepin was started. Risperidone 0.5 mg at bedtime was initiated. Three weeks later, the nursing staff indicated the patient had returned to his condition prior to initiation of doxepin. The scratching had not diminished over the course of doxepin treatment. The patient’s past medical history included mild chronic obstructive pulmonary disease, type 2 diabetes mellitus, and chronic constipation. Routine medications included glyburide 2.5 mg/d, casanthranol 30 mg with docusate 100 mg, and acetaminophen 650 mg four times daily. He had used an albuterol inhaler, but had not required this in the past two years. Fasting blood glucose during the time he received doxepin was unchanged from previous measurements (103–211 mg/dL). The patient had no history of urinary retention. During the time he was treated for scratching behavior, he twice received courses of sertraline, initiated because of agitation with nursing care, decreasing social interaction, a sad mood, and spending more time in his room. Sertraline was never used concurrently with the previously outlined therapeutic trials and was last discontinued six weeks before the doxepin trial; it also had no effect on his scratching. Discussion.This case represents probable systemic anticholinergic toxicity from topical doxepin administration. 1 Symptoms began on day 2 of therapy; we did not associate doxepin with this reaction until day 14. Symptoms significantly improved over the following weeks. Doxepin has significant antihistaminic properties, and the topical formulation is marketed as an antipruritic. Systemic absorption from topically administered doxepin is well documented. The manufacturer 2 states that serum concentrations from undetectable to 47 ng/mL were found in 19 patients with eczema treated with topical doxepin for eight days. Drake et al. 3 treated 24 adults with acute atopic dermatitis for eight days. On day 8, serum concentrations were undetectable (<5 μg/L) in five patients. In the remaining patients, concentrations varied from 5 to 67 μg/L. The therapeutic serum concentrations of doxepin for depression are 30–150 μg/L. The prescribing information 2,4 for topical doxepin indicates drowsiness as the most common systemic adverse effect. Other possible anticholinergic adverse effects described included dry mouth and emotional changes. Delirium, urinary retention, and constipation are not mentioned. Sedation from topical doxepin has been reported during clinical trials. Additionally, two case reports 5,6 of severe doxepin toxicity in children from topical application have been published. Toxic symptoms with anticholinergic agents may include dry mouth, blurred vision, sinus tachycardia, constipation, urinary retention, and delirium. Our patient demonstrated urinary retention and delirium. He also had a stool impaction during doxepin therapy; however, he had a history of chronic constipation. The nurses’ observation of “thick-tongued” may have represented dry mouth. The patient’s blood pressure and heart rate were never elevated. The patient’s age and dementia may have predisposed him to these reactions. His skin was abraded, which may have enhanced drug absorption. The events described here suggest that topical doxepin was the cause of the hallucinations and aggressive behavior, although we cannot support this with more objective information. Unfortunately, we did not obtain a doxepin concentration during the time our patient was experiencing toxic symptoms. Rechallenge with doxepin was not considered clinically appropriate. The fact that his confusion did not resolve completely after the doxepin is difficult to evaluate because of the unpredictable course of dementia. Possible systemic adverse events must be considered when topical doxepin cream is used. Increased adverse drug reaction monitoring of patients using doxepin cream is recommended.

Clinical pharmacy: an evolving area of pharmacy practice in India

Abstract: Prior to 1997, clinical pharmacy teaching and practice were virtually non-existent in India. However, this changed as a result of a joint Indo-Australian program of cooperation between the Repatriation General Hospital in South Australia and the JSS Colleges of Pharmacy in India. Postgraduate courses in clinical pharmacy practice and departments of clinical pharmacy have now been established at several colleges of pharmacy and hospitals respectively. In 2000 the Karnataka Lingayat Education Society (KLES) College of Pharmacy established a Department of Clinical Pharmacy at KLES Hospital in Belgaum, South India. This paper discusses the recent development of clinical pharmacy in India and describes the introduction of clinical pharmacy practice at KLES Hospital. It also reports on three pharmacy conferences held in India in 2000. (author abstract)