Pharmacy Division Ramathibodi Hospital

Home
Pharmacist
About
รอบรู้เรื่องยา
คุยกันเรื่องยา


News 10/05/2545


LORATIDINE LINKED TO BIRTH DEFECTS IN EUROPE
The European Medicines Evaluation Agency (EMEA) announced a safety review of Schering-Plough's hayfever drug loratidine (Clarityn) after reports of an unusually high number of birth defects in children born to mothers who used the drug while pregnant.

GLAXO'S AVANDIA AND TAKEDA'S ACTOS GET STRENGTHENED CARDIOVASCULAR WARNINGS
GlaxoSmithKline and Takeda Pharmaceuticals are modifying the labels of their type II diabetes drugs to more clearly outline the potential cardiovascular risks associated with the drugs, according to documents released by the US Food and Drug Administration (FDA).

NSAIDS TRIPLE RISK OF SEVERE UPPER GI EVENTS
The results of a meta-analysis of cohort and case control studies of severe upper gastrointestinal (GI) complications suggest that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk of perforation, ulcers, and bleeds by a factor of approximately three.

ACUTE MANIC PSYCHOSIS INDUCED BY TRIPLE THERAPY FOR H PYLORI
Patients with multiple chronic diseases can be taking multiple medications, increasing the risk for drug interactions.


Loratidine Linked to Birth Defects in Europe


LONDON (Reuters Health) Apr 25 - The European Medicines Evaluation Agency (EMEA) announced on Thursday a safety review of Schering-Plough's hayfever drug loratidine (Clarityn) after reports of an unusually high number of birth defects in children born to mothers who used the drug while pregnant.

The drug is sold by the name Claritin in the US.

An agency spokesman said that the agency had been told by Sweden of 15 cases of hypospadia out of 2780 children born to mothers taking the drug in early pregnancy. Because the 2780 children included both girls and boys, the actual rate of hypospadia may be twice as high.

The spokesman said that number of hypospadia cases reported in Sweden was about three times higher than normal. However, there had been no reports from any other European country.

"The product has not been withdrawn, but the Committee for Proprietary Medicinal Products...will be looking at these reports over the next 3 months. We are not making any judgements at the moment."

Responding to the EMEA announcement, Dr. Robert Spiegel, Schering-Plough's chief medical officer, told Reuters Health: "We have not been able to corroborate this finding in the Swedish birth registry with any other registry worldwide."

"We are confident that these cases constitute random events. Hypospadia is one of the most common birth abnormalities reported anywhere in the world," he continued. Some estimates put the rate as high as 8 per 1000 births. "So the Swedish birth rate is within the range of what you would expect by chance."

.

Glaxo's Avandia And Takeda's Actos Get Strengthened Cardiovascular Warnings


WASHINGTON (Reuters Health) Apr 26 - GlaxoSmithKline and Takeda Pharmaceuticals are modifying the labels of their type II diabetes drugs to more clearly outline the potential cardiovascular risks associated with the drugs, according to documents released on Friday by the US Food and Drug Administration (FDA).

The modifications to the labeling of Glaxo's Avandia (rosiglitazone) and Takeda's Actos (pioglitazone) provide a more explicit alert about the possibility of fluid retention that might lead to or exacerbate congestive heart failure (CHF) in patients taking either drug with or without insulin.

Previously, both drugs carried a class warning to alert physicians about the risk of edema that might result in cardiovascular complications.

The Warnings, Precautions and Adverse Reactions sections of the drugs' labeling have been updated, and the firms have sent letters to healthcare providers alerting them to the changes. The new labels note that post-marketing cases of CHF have been reported.

In the US, Actos is co-marketed by Eli Lilly and Co.

At close of Friday trading on the New York Stock Exchange, Glaxo's shares were down $0.27 to $48.91, while shares of Lilly were down $0.38 at $70.02.


NSAIDs Triple Risk of Severe Upper GI Events


NEW YORK (Reuters Health) Apr 29 - The results of a meta-analysis of cohort and case control studies of severe upper gastrointestinal (GI) complications suggest that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk of perforation, ulcers, and bleeds by a factor of approximately three, US investigators report.

Previously reported meta-analyses were marred by restrictions on type of study and language of publication, and by omission of nonpublished data, Dr. Joshua J. Ofman, of Cedars-Sinai Health System and Zynx Health Inc., in Beverly Hills, California, and associates note. Their analysis, which appears in The Journal of Rheumatology for April, attempts to overcome these restrictions.

The researchers evaluated 4881 published titles and identified randomized controlled trials involving three US Food and Drug Administration studies and 13 published reports regarding outcomes of perforation, ulcers and bleeds. They also evaluated 23 case control studies and 9 cohort studies.

Randomized control trials involved 4431 patients and yielded a pooled odds ratio of 5.36 compared with placebo. Case control studies, which contributed more than 25,000 patients, yielded a pooled odds ratio of 3.0.

When Dr. Ofman's group stratified their analysis according to whether studies were published before or after 1990, they found no significant difference between the results of randomized control trials and case control studies. However, the risk ratio for cohort studies that appeared before 1990 was 2.0, while the risk ratio for those published in 1990 or later was 3.4.

Dr. Ofman and his associates did not address differences between selective and nonselective cyclooxygenase (COX) inhibitors. In an editorial, Dr. Chris J. Hawkey, of the University Hospital Nottingham in the UK, recommends that similar analysis be conducted for both classes of drugs and for non-GI toxicities.

"The challenge of such studies will be to assess the effect of drugs on overall health, morbidity, and mortality," Dr. Hawkey concludes.

J Rheumatol 2002;29:804-812.


Acute Manic Psychosis Induced by Triple Therapy for H pylori


Nancy E. Neff, MD, Grace Kuo, PharmD

J Am Board Fam Pract 15(1):66-68, 2002. © 2002 American Board of Family Practice

Introduction

Commonly used medications can produce uncommon side effects. Patients with one or more chronic diseases can be taking multiple medications, increasing the risk for drug interactions. New-onset psychosis in middle-aged patients who have no history of psychiatric illness should provoke search for reversible causes. Numerous patients are being treated with triple therapy for Helicobacter pylori-associated peptic ulcer disease. We describe case of organic psychosis in patient who recently had triple therapy for H pylori peptic ulcer disease added to her maintenance medications. Previous reports in the medical literature have described psychiatric complications with various components of triple therapy in patients with previously documented psychiatric disorders. When an adverse event occurs, all medications and possible drug interactions should be considered.

Case Report

A 55-year-old woman with history of hypertension, poorly controlled diabetes, arthritis, and dyspepsia was brought to the emergency department because of strange behavior during the previous few days.

She had no previous psychiatric or substance abuse history other than chronic insomnia. She maintained her usual level of activity as homemaker until 4 days before admission, when she began talking more and sleeping less. She declared that God has chosen me as his prophet, and that He was speaking through her. Her husband and friends reported that the patient did not use any alcohol or other substances and did not have any history of drug allergies, fever, head trauma, headache, nausea, vomiting or change in weight. One week earlier she had received new medicines for dyspepsia from her primary care physician. Her husband indicated that she took her maintenance medications of 5 mg of glyburide, combination human insulin, and 10 mg of lisinopril, as well as 500 mg of acetaminophen intermittently. She had been on low-dose amitriptyline (25 mg) therapy, as needed, for insomnia for 5 months. Because her dyspepsia had not responded to ranitidine and omeprazole in the past, these medications were discontinued. One week before admission, she started taking twice daily 500 mg of clarithromycin, 1 g of moxicillin, and 30 mg of lansoprazole for presumed H pylori peptic ulcer disease, as well as 100 mg celecoxib.

The patient was moderately obese, disheveled, middle-aged woman who was alert and oriented to person only, with marked hyperactivity including pacing, tapping furniture, and praying. Her speech was loud but clear, and the content was extremely religious. Her concentration was poor, and she appeared to have auditory hallucinations. Her temperature, blood pressure, heart rate, and respirations were stable. She was agitated and cooperated poorly. There was no evidence of head trauma or nuchal rigidity. When examined, she had clear lung elds on auscultation, an absence of cardiac murmurs or gallops, and no abdominal tenderness. Other than mild hypesthesia in both feet, there were no gross focal neurologic findings.

Initial finger stick blood glucose was 260 mg/dL, and she was started on sliding scale of regular insulin. When she became more combative, the patient was given one dose of intramuscular haloperidol and lorazepam. She was observed during the next 12 hours, and while less agitated, she remained psychotic. She scored 27 out of 30 on Mini Mental Status Examination.[1]

She was admitted to the inpatient psychiatric service. She continued her outpatient dosage regimens of glyburide, combination human insulin, celecoxib, and lisinopril, but the H pylori triple therapy and the amitriptyline was stopped. She received one dose of risperidone but refused subsequent doses. Results of admission laboratory analyses (including complete metabolic profile, complete blood count, thyroid function tests, and urine drug screen) were normal except for hyperglycemia and glycosuria. A chest radiograph was negative for active disease. An electrocardiogram was normal. Her agitation and psychosis cleared within 36 hours after admission. On questioning, the patient indicated that she had taken the amitriptyline as directed and did not exceed the dose. She was discharged with diagnosis of "organic psychosis" - resolved. Follow-up telephone calls to the patient and her primary care physician indicated that she did well after discharge, showing no signs of psychiatric disease after discontinuing triple therapy for H pylori peptic ulcer disease and amitriptyline.

Discussion

This patient developed an acute manic psychosis within 4-day period. There was no evidence of infection, substance abuse, or hypoglycemia to account for her symptoms. The psychosis began approximately 3 days after the initiation of triple therapy with clarithromycin, amoxicillin, and lansoprazole for presumed H pylori peptic ulcer disease and celecoxib for arthritis pain. Serious adverse effects from insulin, glyburide, and lisinopril were believed to be unlikely.

A review of the literature failed to find psychiatric complications that were due to celecoxib and lansoprazole therapy. Paranoid ideation has been reported with amitriptyline.[2] One case of reversible psychosis[3] and one case of hallucinations[4] have been reported with amoxicillin. Clarithromycin, however, was associated with reversible psychosis in 5 patients.[5-7] One patient had been on long-term omeprazole therapy, and another was taking ranitidine without noticeable morbidity until clarithromycin was added. In both these cases,[5] there was lag time of about 1 week between initiation of clarithromycin and the development of mental toxicity, then complete resolution of symptoms in 24 to 36 hours, such as in our patient. Two other cases were in patients with acquired immunodeficiency syndrome being treated for disseminated Mycobacterium avium infection.[6] The fifth case was an elderly patient with soft-tissue infection.[7] Another case of delirium has been reported with clarithromycin in patient who had been stable on long-term fluoxetine for treatment of depression.[8] The mechanism of the psychotic effect might relate to the inhibition of hepatic cytochrome P-450 enzymes. The possibility of drug interactions increases whenever patient receives two (or more) drugs binding to the same P-450 system. With the exception of amoxicillin, the drugs in this case affect number of P-450 isoenzymes (Table 1). Conceivably this patient's manic psychosis could have been secondary to elevated levels of amitriptyline caused by isoenzyme inhibition by clarithromycin. The previous dose of amitriptyline had been low, however, and compliance had been questionable. The mechanism for psychosis as result of clarithromycin alone is unclear,[5,8] particularly since diffusion of the macrolides into the central nervous system is poor.

No medication is completely benign. When patients with several chronic diseases are on several medications, the potential for drug interactions is increased, and careful attention should be paid to the indications for medication use. In such individuals, definitive testing for H pylori should be considered before starting triple therapy for peptic ulcer disease. This case and the others cited suggest that clarithromycin or its interaction with other agents should be considered as possible cause of acute reversible psychosis in such patients.

Tables

Table 1. Medications That Inhibit the Hepatic Cytochrome P-450 Isoenzymes


Drug 1A2 2C9 2C19 2D6 2E1 3A4
Amitriptyline S* S S S   S
Acetaminophen S       S  
Celecoxib   S   (-)    
Lansoprazole     S(-)     S
Risperidone       S    
Insulin (+)          
Clarithromycin (-)         (-)


*S = substrate, (-) = inhibition, (+) = induction.

References

  1. Folstein MF, Folstein SE, McHugh PR. Mini-Mental State: practical method for grading the state of patients for the clinician. J Psychiatr Res 1975;12: 189-98.
  2. Soloff PH, George A, Nathan RS, Schulz PM, Perel JM. Paradoxical effects of amitriptyline on borderline patients. Am J Psychiatry 1986;143:1603-5.
  3. Beal DM, Hudson B, Zaiac M. Amoxacillin-induced psychosis? Am J Psychiatry 1986;143(2):255-6.
  4. Stell IM, Ojo OA. Amoxycillin-induced hallucinations a variant of Hoigne's syndrome? Br J Clin Pract 1996;50:279.
  5. Gomez-Gil E, Garcia F, Pintor L, Martinez JA, Mensa J, de Pablo J. Clarithromycin-induced acute psychoses in peptic ulcer disease. Eur J Clin Microbiol Infect Dis 1999;18:70-1.
  6. Nightingale SD, Koster FT, Mertz GJ, Loss SD. Clarithromycin-induced mania in two patients with AIDS. Clin Infect Dis 1995;20:1563-4.
  7. Cone LA, Sneider RA, Nazemi R, Dietrich EJ. Mania due to clarithromycin therapy in patient who was not infected with human immunodeficiency virus. Clin Infect Dis 1996;22:595-6.
  8. Pollak PT, Sketris IS, MacKenzie SL, Hewlett TJ. Delirium probably induced by clarithromycin in patient receiving fluoxetine. Ann Pharmacother 1995;29:486-8.

Nancy E. Neff, MD, Grace Kuo, PharmD, Department of Family and Community Medicine (NEN, GK), Baylor College of Medicine, Houston


Back To Top © 2001-2009 RxRama ---- All rights reserved.