Gabapentin Induced Hypersensitivity Syndrome

Hypersensitivity syndrome (HSS) is a rare condition that can occur with any drug. Diagnosis is clinically based, with variable symptoms appearing anywhere between one week to three months after the introduction of the implicated drug. A case of HSS due to gabapentin in a 35 years old lady has been published in the Journal of Postgraduate Medicine.

Naranjo's algorithm, a systematic method of objectively determining the probability of adverse drug reaction having occurred, was applied to this case. A score of 6 was calculated, equating to a "probable" adverse reaction to gabapentin.

Source: J Postgrad Med 2007;53:276-7

http://www.jpgmonline.com/text.asp?2007/53/4/276/37527

Risedronate induced transient ocular myasthenia

A case of ocular myasthenia gravis induced by risedronate therapy for osteoporosis in a 81 years old lady has been reported in The Journal of Postgraduate Medicine.

On Applying the Naranjo's adverse drug reactions (ADR) probability scale, a causality assessment was made which categorized this reaction as probable with a score of 7.

Source: J Postgrad Med 2007;53:274-5

http://www.jpgmonline.com/text.asp?2007/53/4/274/37525

Drug rash with eosinophilia and systemic symptoms syndrome due to quinine

A case of a 58 years old male patient with drug rash with eosinophilia and systemic symptoms (DRESS) syndrome due to quinine has been published in the Journal of Postgraduate Medicine.

On Naranjo scale it scored 5, classifying it as a probable adverse drug reaction.

Source: J Postgrad Med 2007;53:272-3

http://www.jpgmonline.com/text.asp?2007/53/4/272/37523

Tobramycin induced Hepatotoxicity

A case of a hepatotoxicity occuring as a result of tobramycin adminstration has been published in the December issue of the Annals of Pharmacotherapy.
Liver enzymes rose when tobramycin therapy was initiated, markedly increased when the tobramycin dose was increased, then resolved upon discontinuation of therapy. Other medication-related causes were ruled out by temporal relationship or rechallenge (aztreonam). Use of the Naranjo probability scale indicated a possible relationship between hepatotoxicity and tobramycin therapy. Other adverse reaction scales specific for evaluation of drug-induced liver disease were also used. Both the Council for International Organizations of Medical Sciences and Maria and Victorino scales indicated a probable likelihood of tobramycin-induced hepatotoxicity.

Reference: The Annals of Pharmacotherapy 2007;41(12): 2061-2065.

http://www.theannals.com/cgi/content/abstract/41/12/2061

Lumiracoxib

The European Medicines Agency (EMEA) has recommended the withdrawal of the marketing authorisations for all lumiracoxib-containing medicines, because of the risk of serious side effects affecting the liver. Lumiracoxib is a non-steroidal anti-inflammatory drug (NSAID) that belongs to the group ‘COX-2 inhibitors’. It is used for symptomatic relief in the treatment of osteoarthritis of the hip and knee.

Source: http://www.emea.europa.eu/pdfs/human/press/pr/PR_Lumiracoxib_57930107en.pdf

Carbamazepine

FDA informed healthcare professionals that dangerous or even fatal skin reactions (Stevens Johnson syndrome and toxic epidermal necrolysis), that can be caused by carbamazepine therapy, are significantly more common in patients with a particular human leukocyte antigen (HLA) allele, HLA-B*1502. This allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including South Asian Indians. Patients with ancestry from areas in which HLA-B*1502 is present should be screened for the HLA-B*1502 allele before starting treatment with carbamazepine. If these individuals test positive, carbamazepine should not be started unless the expected benefit clearly outweighs the increased risk of serious skin reactions. Patients who have been taking carbamazepine for more than a few months without developing skin reactions are at low risk of these events ever developing from carbamazepine. This is true for patients of any ethnicity or genotype, including patients positive for HLA-B*1502.

Source: http://www.fda.gov/cder/drug/InfoSheets/HCP/carbamazepineHCP.htm

Radio Frequency Ablation Devices

FDA alerted healthcare professionals of reports of patient deaths associated with the use of radio frequency (RF) ablation devices during lung tumor ablation. Patient selection, subsequent treatment, and technical use of the RF device, including placement and operation, may have contributed to the fatalities. While RF ablation devices have been cleared for general indications- ablation of soft tissue by thermal coagulation necrosis- the devices have not been cleared specifically for lung tumor ablation. Healthcare professionals should use caution when operating RF ablation devices, adhering strictly to information contained in the labeled operating instructions, Operators Manual, the Manufacturer's Instructions for Use and any training provided. Additionally, if healthcare professionals plan to use RF ablation devices to treat patients with lung tumors, they should consider enrolling patients in an approved clinical study, where training is available.

Source: http://www.fda.gov/cdrh/safety/121107-rfablation.html

Electric Dental Handpieces

FDA informed healthcare professionals about serious patient injuries, including third degree burns, associated with the use of poorly maintained electric dental handpieces during dental procedures. Some patients had third degree burns which required plastic surgery. Burns may not be apparent to the operator or the patient until after the tissue damage occurred, because the anesthetized patient cannot feel the tissue burning and the handpiece housing insulates the operator from the heated attachment. Although the reported burns occurred during the cutting of tooth and bone, tooth extraction and other dental surgical procedures, overheating can also occur during any dental procedure. This problem is not limited to dentistry. Rotary surgical handpieces can cause patient burns during orthopedic procedures, as reported in the July 2003 edition of FDA Patient Safety News (http://www.fda.gov/cdrh/psn/show17-burns.html). Read the FDA Public Health Notification for specific actions to prevent or minimize serious patient injuries associated with using electric dental handpieces.

Source: http://www.fda.gov/cdrh/safety/121207-dental.html

PedvaxHIB [Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)] COMVAX [Haemophilus b Conjugate (Menigococcal Protein Conjugate)

Merck & Co. and FDA informed healthcare professionals and consumers of a voluntary recall of eleven lots of PedvaxHIB and two lots of COMVAX vaccines. The vaccines were recalled because the manufacturer cannot assure sterility of the affected lots. Routine testing of the vaccine manufacturing equipment used to produce PedvaxHIB and COMVAX identified the presence of Bacillus cereus bacteria. Sterility tests of the vaccine lots themselves have not found any contamination. The affected doses were distributed in the U.S. starting in April 2007. Healthcare professionals should immediately discontinue use of any of the affected lots and follow the manufacturer's instructions for returning recalled vaccines. See the FDA Consumer Update (link given below) for a list of the specific lots of each vaccine recalled.

Source: http://www.fda.gov/consumer/updates/hib121307.html

Cardiac Risks associated with Omeprazole

FDA informed healthcare professionals of the issuance of the Agency's follow-up communication regarding its review of safety data for the drugs omeprazole and esomeprazole that raised concerns about a potential increased risk of heart problems for patients treated with these drugs. The Agency conducted a comprehensive review of the data from two studies that were submitted to FDA. FDA continues to believe that long-term use of omeprazole or esomeprazole is not likely to be associated with an increased risk of heart problems and recommends that healthcare providers continue to prescribe and patients continue to use these products in the manner described in the labeling for the two products.

Source: http://www.fda.gov/cder/drug/early_comm/omeprazole_esomepazole_update.htm

Cefepime

FDA issued an early communication about the ongoing review of new safety data and the request for additional data to further evaluate the risk of death in patients treated with cefepime. An article in the May 2007 issue of The Lancet Infectious Diseases (Efficacy and safety of cefepime: a systematic review and meta-analysis) raised the question about increased mortality with the use of cefepime, a broad spectrum B-lactam antibiotic currently approved for the treatment of a variety of infections due to susceptible strains of microorganisms. The article describes a higher all-cause mortality in patients treated with cefepime compared to other B-lactam antibiotics. Until FDA's evaluation is completed, healthcare professionals who are considering the use of cefepime should be aware of the risks and benefits described in the product's prescribing information and the new information from this meta-analysis.

Source: http://www.fda.gov/cder/drug/early_comm/cefepime.htm

Varenicline and Neuropsychiatric disorders

FDA informed healthcare professionals of reports of suicidal thoughts and aggressive and erratic behavior in patient who have taken Chantix, a smoking cessation product. There are also reports of patients experiencing drowsiness that affected their ability to drive or operate machinery. FDA is currently reviewing these cases, along with other recent reports. A preliminary assessment reveals that many of the cases reflect new-onset of depressed mood, suicidal ideation, and changes in emotion and behavior within days to weeks of initiating Chantix treatment. The role of Chantix in these cases is not clear because smoking cessation, with or without treatment, is associated with nicotine withdrawal symptoms and has also been associated with the exacerbation of underlying psychiatric illness. However, not all patients described in the cases had preexisting psychiatric illness and not all had discontinued smoking.

Healthcare professionals should monitor patients taking Chantix for behavior and mood changes. Patients taking this product should report behavior or mood changes to their doctor and use caution when driving or operating machinery until they know how quitting smoking with Chantix may affect them.

Source: http://www.fda.gov/cder/drug/early_comm/varenicline.htm

Myfortic (mycophenolic acid) Delayed-Release Tablets

Novartis and FDA informed healthcare professionals and patients that use of Myfortic Delayed- Release Tablets during pregnancy is associated with increased risks of pregnancy loss and congenital malformations. The pregnancy category for Myfortic has been changed to Category D (Positive evidence of fetal risk). This change is a result of postmarketing data from the United States National Transplantation Pregnancy Registry and additional postmarketing data collected in women exposed to systemic mycophenolate mofetil (MMF) during pregnancy.

MMF is converted to the active ingredient in Myfortic, following oral or intravenous administration. A patient who is planning a pregnancy should not use Myfortic unless she cannot be successfully treated with other immunosuppressant drugs. Healthcare professionals should discuss the risks and benefits of Myfortic as well as alternative immunosuppressant therapy with the patient. Female patients of childbearing potential must receive contraceptive counseling and must use effective contraception while taking Myfortic. Myfortic is indicated for the prophylaxis of organ rejection in patients receiving allogeneic renal transplants, administered in combination with cyclosporine and corticosteroids.

Source: http://www.fda.gov/medwatch/safety/2007/Myfortic_DHCP_Letter.pdf

Flu drugs and neuropsychiatric changes.

The FDA’s Pediatric Advisory Committee has recommended changing the label of Roche’s flu medication Tamiflu to reflect the potential for neuropsychiatric adverse events, but it did not specify what changes should be made.

The relationship between Tamiflu (oseltamivir phosphate) and neuropsychiatric adverse events, including suicides, cannot be determined, the FDA said. Committee members proposed including an indication that the adverse events are sometimes fatal and adding language showing the uncertainty over the drug’s causal effect.

The committee also voted to change the labeling of GlaxoSmithKline’s (GSK) Relenza (zanamivir) to reflect an increase in adverse event reports but did not determine what the changes should be or whether the label should be the same as Tamiflu’s.

Last year, Roche revised its Tamiflu package insert to add warnings about the potential for self-injury and confusion, particularly in pediatric patients. Twenty-five patients younger than 21 years old have died while taking Tamiflu, with 21 of the cases occurring in Japan and three in the U.S. Five of the deaths came from children “falling from windows or balconies or running into traffic,” the FDA said.

Source: FDA News

Teratogenicity associated with mycophenolate mofetil

Roche and FDA notified healthcare providers that use of CellCept (mycophenolate mofetil) is associated with increased risk of first trimester pregnancy loss and increased risk of congenital malformations, especially external ear and facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, and kidney.

Based on postmarketing data from the United States National Transplantation Pregnancy Registry and additional postmarketing data collected in women exposed to systemic mycophenolate mofetil during pregnancy, the pregnancy category for CellCept has been changed from Category C (risk of fetal harm cannot be ruled out) to Category D (positive evidence of fetal risk).

Within one week of beginning CellCept therapy, women of childbearing potential should have a negative serum or urine pregnancy test. In addition, women of childbearing potential (including pubertal girls and peri-menopausal woman) taking CellCept must receive contraceptive counseling and use effective contraception. Healthcare professionals and patients should be aware that CellCept reduces blood levels of the hormones in the oral contraceptive pill and could theoretically reduce its effectiveness.

Source: http://www.fda.gov/medwatch/safety/2007/CellCept_dearhcpoct07.pdf

Intramuscular Methotrexate-Induced Aseptic Meningitis

A case of a 62-year-old male presenting on 3 separate occasions with symptoms consistent with aseptic meningitis: 2 requiring hospitalization and 1 noted during a subsequent ambulatory care visit, has been published in the latest issue of Annals of Pharmacotherapy.

Methotrexate-induced aseptic meningitis has been reported in the literature; however, in those cases, the effect occurred only when methotrexate was given via the intrathecal route. The Naranjo probability scale indicates a probable relationship between the development of the condition and the methotrexate use in this patient.

Source: The Annals of Pharmacotherapy 2007;41(11):1906-1911.

http://www.theannals.com/cgi/content/abstract/41/11/1906

FDA Advisory Committees Recommend Against Cough and Cold Medications in Children Under 6

Citing a lack of proven effectiveness and a need for clinical trials in children, the FDA’s Nonprescription Drugs and Pediatric Advisory Committees recommended the ingredients in cough and cold medications not be used in children younger than 6.

The agency convened a two-day meeting in response to a citizen petition requesting the FDA not allow the drugs to be marketed for children younger than 6. The petition was filed by the Baltimore City Health Department on behalf of several hospitals and universities. Although the petitioners’ request applies to children younger than 6, the agency told the committees any actions it takes could apply to children younger than 12.

The FDA is not required to accept advisory committee recommendations but usually does. Petitioners testifying to the committees argued, based on review of published studies, that cough and cold products intended for use in children have not been proven effective. Therefore, any adverse events associated with their use in the respective patient populations are not appropriate, and use of the drugs in children should be limited.The FDA agreed that the drugs have not been shown to be effective but said it was important to consider the studies were not well designed. If the agency were to act on the advisory committees’ recommendations, it would have to start the rulemaking process.

The panel voted unanimously that the products should not be used in children younger than 2 and voted 13-9 against use in those between the ages of 2 and 6. The committees did not recommend against use of the drugs in children between the ages of 6 and 12, with seven members voting to ban it and 15 not to. However, the members voted unanimously that cough and cold medicines have not been shown effective in children younger than 12.

Source: http://news.google.co.in/news?hl=en&ned=in&q=FDA

Sildenafil, Tadalafil and Vardenafil.

FDA informed healthcare professionals of reports of sudden decreases or loss of hearing following the use of PDE5 inhibitors Viagra (Sildenafil), Levitra (Vardenafil), Cialis (Tadalafil) for the treatment of erectile dysfunction, and Revatio (Sildenafil) for the treatment of pulmonary arterial hypertension.
In some cases, the sudden hearing loss was accompanied by tinnitus and dizziness. Medical follow-up on these reports was often limited which makes it difficult to determine if the loss of hearing was related to the use of one of the drugs, an underlying medical condition or other risk factors for hearing loss, a combination of these factors or other factors.
The PRECAUTIONS and ADVERSE REACTIONS sections of the approved product labeling for Viagra, Levitra, and Cialis were revised. FDA is working with the manufacturer to revise the labeling for Revatio.

Source: http://www.fda.gov/medwatch/safety/2007/safety07.htm

Acute Pancreatitis Associated with Exenatide

FDA has reviewed 30 postmarketing reports of acute pancreatitis in patients taking exenatide, a drug used to treat adults with type 2 diabetes. An association between Exenatide and acute pancreatitis is suspected in some of these cases.

Healthcare professionals should be alert to the signs and symptoms of acute pancreatitis and instruct patients taking Exenatide to seek prompt medical care if they experience unexplained, persistent, severe abdominal pain which may or may not be accompanied by vomiting. If pancreatitis is suspected, Exenatide should be discontinued. If pancreatitis is confirmed, Exenatide should not be restarted unless an alternative etiology is identified.

Source: http://www.fda.gov/cder/drug/infopage/exenatide/default.htm

Atrial Fibrillation associated with Bisphosphonates

FDA issued an early communication about the ongoing review of new safety data regarding the association of atrial fibrillation with the use of bisphosphonates. Bisphosphonates are a class of drugs used primarily to increase bone mass and reduce the risk for fracture in patients with osteoporosis, slow bone turnover in patients with Paget’s disease of the bone, treat bone metastases, and lower elevated levels of blood calcium in patients with cancer. FDA reviewed spontaneous postmarketing reports of atrial fibrillation reported in association with oral and intravenous bisphosphonates and did not identify a population of bisphosphonate users at increased risk of atrial fibrillation.

In addition, as part of the data review for the recent approval of once-yearly Reclast (Zoledronic Acid) for the treatment of postmenopausal osteoporosis, FDA evaluated the possible association between atrial fibrillation and the use of Reclast. Most cases of atrial fibrillation occurred more than a month after drug infusion. Also, in a subset of patients monitored by electrocardiogram up to the 11th day following infusion, there was no significant difference in the prevalence of atrial fibrillation between patients who received Reclast and patients who received placebo.

Upon initial review, it is unclear how these data on serious atrial fibrillation should be interpreted. Therefore, FDA does not believe that healthcare providers or patients should change either their prescribing practices or their use of bisphosphonates at this time.

Source: http://www.fda.gov/cder/drug/early_comm/bisphosphonates.htm

FDA Takes Action To Stop Marketing Of Unapproved Hydrocodone Products

FDA informed healthcare professionals and consumers of its intent to take action against companies that market unapproved prescription products containing hydrocodone, a narcotic widely used as a coughsuppressant and to treat pain.

The drug has also been an extremely popular drug of abuse and can lead to serious illness, injury, or death,if improperly used. Hydrocodone overdose can result in breathing problems or cardiac arrest, and its use may impair motor skills andjudgment. The FDA has received reports of medication errors associated withformulation changes in unapproved hydrocodone products and reports of confusion over the similarity of the names of unapproved products to approved drug products. Most of the hydrocodone formulations now marketed to suppress coughs have not been approved. The agency isparticularly concerned about improper pediatric labeling of unapproved hydrocodone cough suppressants (also known as antitussives), and the risk of medication error involving the unapproved products.

No hydrocodone cough suppressant has been established as safe and effective for children under 6 years of age and some of these unapproved products carry labels with dosing instructions for children as young as 2 yearsof age. Anyone marketing unapproved hydrocodone products that are currently labeled for use in children younger than 6 years of age must end further manufacturing and distribution of the products on or before October 31,2007.

Those marketing any other unapproved hydrocodone drug products must stop manufacturing such products on or before December 31, 2007,and must cease further shipment in interstate commerce on or beforeMarch 31, 2008. Further legal action could be taken against those failing to meet these deadlines. There are a number of alternatives for patients who might be using unapproved hydrocodone cough suppressants. Consumers should consult ahealthcare professional for detailed guidance on treatment options.

Source: http://www.fda.gov/medwatch/safety/2007/safety07.htm#Hydrocodone

The number of Serious Adverse Events doubles in seven years in the US

The number of reported serious adverse events from drug treatment more than doubled in the United States from 1998 to 2005, rising from 34,966 to 89,842.

Over the same period the number of deaths relating to drugs nearly tripled, from 5519 to 15 107, show data from the US Food and Drug Administration's adverse event reporting system, which collects all reports of adverse events submitted voluntarily to the agency either directly or through drug manufacturers.

Source: Archives of Internal Medicine 2007;167:1752-9.

BMJ 2007;335:585 (22 September), doi:10.1136/bmj.39339.624711.DB

http://www.bmj.com/cgi/content/extract/335/7620/585-a

Oral Aloe Vera induced Hepatitis

A case of a 73-year-old female admitted to the hospital for acute hepatitis has been published in the Annals of Pharmacotherapy. Extensive laboratory testing did not reveal the cause of the patient's disease. She was asked multiple times whether she was taking any home medications, which she initially denied. It was only after an extensive medication history done by a clinical pharmacist that the patient admitted to using oral aloe vera capsules for constipation. Upon discontinuation of the oral aloe vera, liver markers of hepatotoxicity returned to normal levels.

Using the Roussel Uclaf Causality Assessment Method for determining drug hepatotoxicity, the patient's symptoms were scored as probably caused by oral aloe vera.

Source: The Annals of Pharmacotherapy 2007;41(10):1740-1743.

http://www.theannals.com/cgi/content/abstract/41/10/1740

Visual Loss associated with Povidone-Iodine Pleurodesis

Three cases of bilateral severe loss of vision (ranging from 20/800 vision to the perception of hand motions only) after thoracoscopic surgery involving resection of parts of one lung and instillation of 200 to 500 ml of Jodobac, a 10% povidone–iodine solution, into the thoracic cavity for disinfection and to cause scarring of the pleura for prophylaxis against pneumothorax have been reported in the latest issue of the New England Journal Of Medicine.

Source: NEJM 2007;357(12):1264-65.

http://content.nejm.org/cgi/content/full/357/12/1264

Aplastic Anemia associated with Temozolomide

A safety review of temozolomide identified cases of aplastic anemia, some fatal, associated with use of the drug. Healthcare professionals should be alert to the possibility of aplastic anemia in the setting of refractory or prolonged myelosuppression in patients receiving temozolomide and report cases to FDA's MedWatch.

From August 11, 1999, to November 3, 2006, FDA received 18 (domestic-14, foreign-4) reports of aplastic anemia among patients receiving temozolomide. Product labeling currently includes a warning regarding myelosuppression and describes pancytopenia among reported adverse events.

Source: http://www.fda.gov/cder/dsn/2007_fall/postmarketing.htm#Temozolomide

Serious Skin Reactions Associated with Modafinil

Modafinil (Provigil) is an oral wakefulness-promoting agent to treat patients with excessive sleepiness (ES) associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSAHS), and shift work sleep disorder (SWSD).

FDA has been monitoring cases of serious skin reactions, including erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), in its postmarketing reviews of adverse event reports associated with the use of modafinil. The product labeling for modafinil has been recently updated to include a bolded warning for serious rash, including SJS.

Source: http://www.fda.gov/cder/dsn/2007_fall/postmarketing.htm#modafinil

Progressive Multifocal Leukoencephalopathy (PML) associated with Rituximab

A safety review on rituximab identified an association of the drug with a serious adverse event, progressive multifocal leukoencephalopathy (PML), a viral infection of the central nervous system. The product labeling has been updated to reflect this new safety information, and a public health advisory and information for healthcare professionals have been posted on FDA's Web site.
As of December 2006, FDA has received a total of 24 reports of PML in patients who received rituximab treatment.

Source: http://www.fda.gov/cder/dsn/2007_fall/postmarketing.htm#Rituximab

Cardiovascular Risk with Haloperidol

Johnson and Johnson and FDA informed healthcare professionals that the WARNINGS section of the prescribing information for haloperidol has been revised to include a new Cardiovascular subsection regarding cases of sudden death, QT prolongation and Torsades de Pointes(TdP) in patients treated with haloperidol, especially when given intravenously, or at doses higher than recommended. Although injectable haloperidol is only approved by the FDA for intramuscular injection, there is considerable evidence that the intravenous administration of haloperidol is a relatively common off-label clinical practice.

There are at least 28 case reports of QT prolongation and TdP, some with fatal outcome in the context of off-label intravenous haloperidol. Healthcare professionals should consider this new risk information when making individual treatment decisions for their patients.

Source: http://www.fda.gov/cder/drug/InfoSheets/HCP/haloperidol.htm

Potential Risk Associated With Concomitant Use Of Ceftriaxone With Calcium Containing Products

Roche informed healthcare professionals about revisions made to the prescribing information for Rocephin (Ceftriaxone Sodium) to clarify the potential risk associated with concomitant use of Rocephin with calcium or calcium-containing solutions or products.

Healthcare professionals are advised that Rocephin and calcium-containing solutions including continuous calcium-containing infusions such as parenteral nutrition, should not be mixed or co-administered to any patient irrespective of age, even via different infusion lines at different sites. Rocephin and IV calcium-containing solutions should not be administered within 48 hours of each other in any patient. No data are available on the potential interaction between ceftriaxone and oral calcium-containing products or interaction between intramuscular ceftriaxone and calcium-containing products (IV or oral).

Source: http://www.fda.gov/medwatch/safety/2007/safety07.htm#Rocephin

valproate-induced hyperammonemic encephalopathy

A case of valproate-induced hyperammonemic encephalopathy in a 18 years old female being prescribed valproate 750mg per day for temporal lobe epilepsy and having normal liver function has been published in Canadian Medical Association Journal.

Source: CMAJ. September 11, 2007; 177 (6). doi:10.1503/cmaj.061272.

http://www.cmaj.ca/cgi/content/full/177/6/568

Viracept (nelfinavir mesylate) and guidance on use in pregnant women and pediatric patients

Pfizer issued a Dear Healthcare Professional Letter to inform healthcare professionals of the presence of ethyl methanesulfonate (EMS), a process-related impurity in Viracept and to provide guidance on the useof Viracept in pregnant women and pediatric patients.

EMS is a potential human carcinogen. Data from animal studies indicate EMS is teratogenic, mutagenic and carcinogenic; however, no data from humans exist. FDA has asked Pfizer to implement new specifications to limit the presence ofEMS in Pfizer-manufactured Viracept products marked in the UnitedStates.

For pediatric patients who are stable on Viracept-containing regimens, FDA and Pfizer agree that the benefit-risk ratio remains favorable and those patients may continue to receive Viracept. Pediatric patients who need to begin HIV treatment should not start regimens containingViracept until further notice. Pregnant women who need to begin antiretroviral therapy should not be offered regimens containingViracept until further notice. As a precautionary measure, pregnant women currently receiving Viracept should be switched to an alternative antiretroviral therapy while Pfizer and FDA work to implement the longterm EMS specification for Viracept. For pregnant women with no alternative treatment options, FDA and Pfizer agree that therisk-benefit ratio remains favorable for the continued use of Viracept.

Source: http://www.fda.gov/medwatch/safety/2007/safety07.htm#Viracept

Acute hepatitis attack after exposure to telithromycin

A case of 25 years old male patient having been prescribed 400 mg of Telithromycin for an upper respiratory tract infection and presenting with Jaundice, nausea and malaise has been published in Clinical Therapeutics.

Pathological Examination revealed 'drug induced toxic hepatitis' and the Naranjo adverse drug reaction probability scale had a score of 8 for this case.

Source: Clin Ther 2007;29:1725-1729.

http://www.clinicaltherapeutics.com/articles/1725_onu.pdf

High-Dose Prexige (Lumiracoxib) Withdrawn in New Zealand

New Zealand’s drug regulatory authority, Medsafe, has canceled the registration of 200- and 400-mg tablets of the Cox-2 inhibitor Prexige after reviewing local and international reports of severe liver damage in patients taking high doses of the drug.

The move comes just over a week after Australia’s Therapeutic Goods Administration (TGA) withdrew Novartis’ pain killer altogether. The TGA’s decision was in response to eight serious reactions, including two deaths and two liver transplants.

The 100-mg Prexige (lumiracoxib) tablet remains on the market in New Zealand. The drug is used for the management of osteoarthritis.

Source: http://www.medsafe.govt.nz/hot/media/2007/Prexige.asp

Acute stroke with high-dose intravenous immune globulin

A case of acute stroke in a 43 years old female patient who was receiving high-dose intravenous immune globulin (IVIG) for dermatomyositis has been published in the American Journal of Health System Pharmacy.

Although rare, stroke associated with thrombosis caused by the administration of IVIG has been reported in the literature. On the basis of the Naranjo probability scale, this adverse drug event was calculated as a probable reaction due to the administration of IVIG.

Source: American Journal of Health-System Pharmacy, Vol. 64, Issue 15, 1611-1614

http://www.ajhp.org/cgi/content/abstract/64/15/1611

Elevated serum transaminase levels resulting from concomitant use of rosuvastatin and amiodarone

The case of a 73 years old female patient whose serum transaminase levels became elevated after concomitant use of rosuvastatin and amiodarone has been published in the current issue of American Journal of Health System Pharmacy.

Source: American Journal of Health-System Pharmacy, Vol. 64, Issue 17, 1818-1821

http://www.ajhp.org/cgi/content/abstract/64/17/1818

Indian Drug Regulator to get serious about Pharmacovigilance

The Indian drug regulator is planning a major overhaul in the country’s drug adverse reaction monitoring system.

The Central Drugs Standard Control Organisation is now planning to appoint a team of about 100 clinical pharmacologists across the country, on a contract basis, to collect adverse drug reaction reports and patient complaints from hospitals, clinics and practising clinicians.

“We are not taking any chances now, because the domestic pharma market is growing and a host of new drugs are being launched by domestic as well as foreign companies,” said M. Venkateswarlu, India’s drug controller general. “Though the new drugs are approved after verifying the clinical trial data, this will not be enough to establish the absolute safety of a drug as these are conducted in limited number of volunteers or patients, which are only indicative. So a regular post-marketing study will only provide the actual response (effects and side effects) of the drug as it has been practically used in a wider patient pool.”

Though it is the responsibility of drug manufacturers to do these studies on newly marketed drugs and submit the data to the regulator, the system has been a failure in India as most companies flout the law.

As a result, the country had hardly any drug recalls, even though several drugs marketed here are alleged to have a doubtful safety profile. The system could also be an early-warning system unlike recent cases, including recall controversies over GlaxoSmithKline Plc.’s Avandia diabetes drug and the voluntary recall of cardiac stents by Johnson & Johnson, where Indian authorities are still seeking information from their Western counterparts and the multinational drug companies.

Source and detailed report: http://www.livemint.com/2007/08/27004814/Drug-regulator-to-monitor-side.html

Eli Lilly to Cease Sale of Pergolide Due to Risk of Cardiac Valvulopathy

Eli Lilly Canada Inc., in collaboration with Health Canada, has informed healthcare professionals that sales of Permax will cease in Canada as of August 30, 2007.

Subsequent to new post-market safety information coming from two papers published in the January 4, 2007 issue of the New England Journal of Medicine (NEJM) that provided further evidence consistent with previous reports of valvulopathy cases in patients taking pergolide,1 2 Health Canada considers that there is insufficient evidence to support the continued safe use of Permax under the current recommendations outlined in the Product Monograph.

Source and detailed report: http://www.docguide.com/news/content.nsf/news/852571020057CCF685257339005C676C?OpenDocument&id=48DDE4A73E09A969852568880078C249&c=Parkinson&count=10

Risperidone- and Quetiapine-Induced Cholestasis

The Annals of Pharmacotherapy describes a case of a patient who developed drug-induced cholestasis after being on risperidone maintenance therapy for 8 years.

A 30-year-old male with schizoaffective disorder, bipolar type, and insulin-dependent diabetes mellitus had been stable on risperidone 6 mg at night for 8 years. His other medications included lithium 900 mg twice daily and enalapril 5 mg daily, as well as regular insulin and NPH insulin as needed. The patient developed cholestasis that resolved once risperidone was discontinued. Over the next 11 months, he tolerated trials of ziprasidone and olanzapine. When quetiapine was initiated, the patient developed signs and symptoms of cholestasis within 3 weeks after starting this medication. The signs and symptoms of cholestasis resolved with removal of quetiapine. The Naranjo probability scale indicated that these atypical antipsychotics (risperidone and quetiapine) were the probable cause of cholestasis in this patient.

Source: Annals of Pharmacotherapy 2007;41(9):1518-1523.
http://www.theannals.com/cgi/content/abstract/41/9/1518

Pegfilgrastim-Induced Hyperleukocytosis

Annals of Pharmacotherapy has reported a pediatric case of pegfilgrastim-induced hyperleukocytosis.

A 3-year-old boy with medulloblastoma therapy presented with white blood cell (WBC) count 0.1 x 103/µL and absolute neutrophil count (ANC) 0.014 x 103/µL on day 27 following a course of induction chemotherapy. The patient received pegfilgrastim 200 µg/kg the following day. On his return 6 days later for the next planned course of chemotherapy, hyperleukocytosis was determined, with WBC 149 x 103/µL and ANC 110 x 103/µL ("neutrophil overshoot"). No sources of the elevated WBC count other than administration of pegfilgrastim (eg, steroids, antiepileptics, infection) were present. Chemotherapy was delayed until the WBC count had fallen to 35.2 x 103/µL (ANC 28.9 x 103/µL). No sequelae from this adverse effect occurred.
Use of the Naranjo probability scale suggested that pegfilgrastim was the probable cause of hyperleukocytosis in the patient.

Source: Annals of Pharmacotherapy 2007;41(9):1524-1530.
http://www.theannals.com/cgi/content/abstract/41/9/1524

Amlodipine-Induced Bilateral Upper Extremity Edema

A case of bilateral upper extremity edema associated with Amlodipine use has been reported in the latest issue of The Annals of Pharmacotherapy.

A previously well and normotensive 6-year-old girl presented with a generalized vasculitis of unknown origin and severe hypertension. Large vessels predominantly affecting the neck, chest, and abdomen were found to be involved, resulting in abnormal arterial circulation and significant blood pressure differences between the upper and lower extremities. Multiple antihypertensive agents were initially required to control blood pressure. She was stabilized and discharged on amlodipine 10 mg each evening, atenolol 50 mg/day, and warfarin. Three days later she was noted to have facial and bilateral upper extremity pitting edema. Laboratory and radiologic assessments for possible etiologies were negative. Discontinuation of amlodipine resulted in resolution of edema. According to the Naranjo probability scale, amlodipine was a probable cause of bilateral upper extremity edema in this child.

Source: The Annals of Pharmacotherapy 2007;41(9):1536-38.
http://www.theannals.com/cgi/content/abstract/41/9/1536

Thiazolidinediones (Glitazones)

After a review of postmarketing adverse event reports, FDA determined that an updated label with a boxed warning on the risks of heart failure was needed for the entire thiazolidinedione class of antidiabetic drugs. These drugs are used in conjunction with diet and exercise to improve blood sugar control in adults with type 2 (non-insulin-dependent) diabetes. Manufacturers of certain drugs have agreed to the upgraded warning.

The strengthened warning advises healthcare professionals to observe patients carefully for the signs and symptoms of heart failure, including excessive, rapid weight gain, shortness of breath, and edema after starting drug therapy. Patients with these symptoms who then develop heart failure should receive appropriate management of the heart failure and use of the drug should be reconsidered. People who have questions should contact their healthcare providers to discuss alternative treatments.

Source: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01683.html

Nonprescription Cough and Cold Medicine Use in Children

FDA announced that on October 18 - 19, 2007, the Nonprescription Drugs Advisory Committee will discuss the safety and effectiveness of cough and cold drug product use in children. Questions have been raised about the safety of these products and whether the benefits justify any potential risks from the use of these products in children, especially in children under two years of age. In preparation for the meeting, FDA is reviewing safety and efficacy data for the ingredients of these products.

Some reports of serious adverse events associated with the use of these products appear to be the result of giving too much of these medicines to children. An over-the-counter cough and cold medicine can be harmful if more than the recommended amount is used, if it is given too often, or if more than one cough and cold medicine containing the same active ingredient are being used. To avoid giving a child too much medicine, parents must carefully follow the directions for use of the product in the “Drug Facts” box on the package label. The Public Health Advisory offers parents and caregivers of children recommendations when using cough and cold products in children.

Complete Advisory: http://www.fda.gov/cder/drug/advisory/cough_cold.htm

Lopinavir/ Ritonavir Oral Solution (Kaletra)

Abbott Laboratories disseminated a Dear Healthcare Provider Letter throughout the world to physicians and pharmacists that prescribe/distribute Kaletra Oral Solution. The letter informed healthcare professionals of an accidental overdose that occurred with a pediatric patient taking Kaletra Oral Solution. The infant received a significantly large dose of Kaletra and subsequently died. Healthcare professionals should pay special attention to accurate calculation of the dose of Kaletra, transcription of the medication order, dispensing information and dosing instructions to minimize the risk for medication errors.

Source: http://www.fda.gov/medwatch/safety/2007/safety07.htm#kaletra

Dear Healthcare Professional Letter - Abbot [PDF]: http://www.fda.gov/medwatch/safety/2007/Kaletra_DHCP.pdf

Australian Medicines Regulator cancels registration of Lumiracoxib

Australia's medicines Regulator, the Therapeutic Goods Administration (TGA) has cancelled the registration of the osteoarthritis drug, Lumiracoxib because of serious liver side effects associated with the use of the drug.

Lumiracoxib, marketed by Novartis Pharmaceuticals under the brand name of Prexige, is a Cox 2 inhibitor belonging to the group of medicines known as non-steroidal anti-inflammatory drugs (NSAIDS).

As of 10 August 2007, the TGA had received eight reports of serious liver adverse reactions associated with use of lumiracoxib, including two deaths and two patients requiring liver transplants. All these reports have been received since March 2007, with 6 reports received in the last 6 weeks. The TGA has urgently investigated these reports and as a result has acted to deregister the drug to prevent further cases of liver damage related to lumiracoxib.

Although there is limited data on the natural history of the hepatic side effects of lumiracoxib, the pre-registration clinical trial data suggested that if a patient developed elevated liver function tests while on the drug, they were likely to normalise their biochemistry when the lumiracoxib was ceased. However, in the 8 serious Australian reports studied, some patients have not improved on cessation of the medicine, due to the severity of the hepatic injury.

The TGA and its expert advisory committee, the Adverse Drug Reactions Advisory Committee (ADRAC), have urgently investigated these reports. ADRAC has today recommended the cancellation of the registration of Lumiracoxib due to the severity of the reported side effects associated with this drug.

The regulator has labelled it as a Class I defect. Class I defects are potentially life-threatening or could cause a serious risk to health.

The TGA has thus advised that all patients cease taking lumiracoxib immediately, and are assessed by their doctor for any clinical or biochemical evidence of liver damage.

Recall letters are expected to be dispatched by the sponsor within the next week.

Source: http://www.tga.gov.au/alerts/prexige.htm

http://www.tga.gov.au/recalls/2007/lumiracoxib.htm

http://www.tga.gov.au/media/2007/070811-lumiracoxib.htm

European Commission Suspends Roche's License To Market Antiretroviral Viracept (Nelfinavir)

The European Commission has suspended Swiss drugmaker Roche's licence to market the HIV drug Viracept (Nelfinavir) in the European Union.

"The suspension is due to the contamination of certain lots of Viracept with ethyl mesilate, a genotoxic substance," the EU executive said in a statement.

The suspension follows the withdrawal of the drug from the market in June when Roche said its licence for Viracept was being temporarily suspended pending a review by authorities.

The Commission said Tuesday's announcement was based on the scientific conclusions from the European Medicines Agency (EMEA) and consultations with EU member states.

"The suspension could only be lifted by a further decision by the Commission, after the evaluation of new data given by the Agency," the EU executive said.

In June, Roche said it had identified a chemical impurity in the product, leading to the recall in Europe and some other regions.

Source: http://www.reuters.com/article/companyNewsAndPR/idUSL0734726920070807

Early Communication About an Ongoing Safety Review - Omeprazole and Esomeprazole

FDA issued an early communication about the ongoing review of new safety data for the proton pump inhibitors, Prilosec (Omeprazole) and Nexium (Esomeprazole). The new safety data was from two small long-term clinical studies in patients with severe gastroesophageal reflux disease (GERD). In both studies, patients were randomly assigned to receive treatment with a drug (either omeprazole or esomeprazole) or to have surgery to control their GERD.

The results from the study of Prilosec and analyses from an ongoing study of Nexium raised concerns that long-term use of Prilosec or Nexium may have increased the risk of heart attacks, heart failure, and heart-related sudden death in those patients taking either one of the drugs compared to patients who received surgery. After reviewing these and other data submitted by the company, FDA's preliminary conclusion at this time, is that collectively, these data do not suggest an increased risk of heart problems for patients treated with omeprazole or esomeprazole. Healthcare providers should not change their prescribing practices and patients should not change their use of these products at this time.

Source: http://www.fda.gov/cder/drug/early_comm/omeprazole_esomeprazole.htm

Potential Drug Interactions with Tizanidine

Acorda Therapeutics recently alerted healthcare professionals about new contraindications for Zanaflex. Zanaflex (tizanidine) is used to treat spasticity.

New labeling says that this drug should not be used concomitantly with either of two CYP1A2 inhibitors: fluvoxamine, which is used to treat depression and anxiety disorders, or the antibiotic ciprofloxacin. Taking either of these drugs together with tizanidine can cause dangerously elevated serum levels of tizanidine, which can lead to side effects such as severe hypotension and sedation. The company says that other CYP1A2 inhibitors may also lead to substantial increases in tizanidine blood concentrations, although there have been no clinical studies to substantiate this. Therefore, using tizanidine with other CYP1A2 inhibitors should ordinarily be avoided. These drugs include zileuton, other fluoroquinolones, antiarrythmics, H-2 blockers, oral contraceptives, acyclovir and ticlopidine.

Source: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/psn/transcript.cfm?show=66#7

New Warnings on Defarasirox

Novartis has notified healthcare professionals that new warnings have been added to the labeling for Exjade (defarasirox). Exjade is used to treat transfusional hemosiderosis, the chronic iron overload that can result from blood transfusions.

Cases of acute renal failure, some of them fatal, have been reported in patients taking this drug. Most occurred in patients with multiple co-morbidities who were in advanced stages of their hematological disorders.

Before beginning therapy with Exjade, all patients should have their serum creatinine assessed in duplicate to establish a baseline level, and then creatinine should be monitored monthly during treatment. Patients who may be at increased risk of complications should be monitored weekly during the first month of Exjade therapy or when the treatment is modified, and then monthly thereafter. These high-risk patients include the elderly, people with pre-existing renal disease or other co-morbid conditions, and those receiving drugs that can depress renal function. There have also been reports of cytopenias in patients on Exjade, some of them fatal. The relationship between the drug and these effects is uncertain, since most of the patients had pre-existing hematological disorders that themselves are associated with bone marrow failure. Blood counts should be monitored regularly and treatment interrupted in patients who develop unexplained cytopenia.

Source: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/psn/transcript.cfm?show=66#4

Avandia to stay on Market

A federal drug advisory committee voted overwhelmingly on Monday to recommend that the diabetes drug Avandia remain on the market, even after finding that it raised the risks of heart attacks.

Panel members said that studies concerning Avandia were too murky to merit drastic regulatory action and that other diabetes medicines might have similar risks.

Source: http://www.nytimes.com/2007/07/31/health/31drug.html?hp

Bisphosphonate induced Osteonecrosis of the Jaw [BONJ]

Bisphosphonate associated osteonecrosis of the jaws (BONJ) has been well documented recently in relation to intravenous preparations of the drug. These are most commonly used as part of the management of hypercalcaemia of malignancy and metastatic bone disease but BONJ can also occur in association with oral bisphosphonate use. The oral preparations can also be prescribed in the management of metastatic bone disease but are more commonly used for the prevention and treatment of osteoporosis.

Three case reports have been published in the British Dental Journal in which alendronate, risedronate and ibandronate have been associated with osteonecrosis of the jaws.The authors conclude, in agreement with other published authors, that prevention and early detection could be improved to reduce the occurrence and severity of this condition. However when BONJ is diagnosed, the early application of a closely monitored conservative regimen, with consideration given to discontinuation of the bisphosphonate, may give the best chance of containing or resolving the condition.

Source: British Dental Journal 2007;203:93-97.

http://www.nature.com/bdj/journal/v203/n2/full/bdj.2007.636.html

Antidepressant induced Liver injury

Antidepressant-induced liver injury described in published cases were of the idiopathic type and, by definition, cannot be predicted based on dose or specific risk factors. Paroxetine had the largest number of cases within the selective serotonin-reuptake inhibitor class. Nefazodone, a serotonin-norepinephrine reuptake inhibitor, appeared to have the most serious cases and is the only antidepressant agent that carries a Food and Drug Administration Black Box Warning regarding hepatotoxicity. The tricyclic antidepressants and monoamine oxidase inhibitors are capable of producing hepatotoxicity, but fewer cases with these agents have been reported in the past 15 years, possibly due to a decline in their use. Causality has not been well established in all reports due to the concurrent use of other drugs and/or underlying liver disease.

Most antidepressant agents have the potential to produce idiopathic liver injury. There is no way to prevent idiopathic DILI, but the severity of the reaction may be minimized with prompt recognition and early withdrawal of the agent. The clinician must be careful to provide ongoing therapy of the underlying depressive disorder and be aware of possible drug discontinuation syndromes should potential hepatotoxicity be suspected.

Source: The Annals of Pharmacotherapy 2007;41(7):1201-1211.

http://www.theannals.com/cgi/content/abstract/41/7/1201

Rabeprazole induced Neuropsychiatric Symptoms

A case of a patient who developed marked anxiety associated with episodes of panic attacks after starting rabeprazole therapy has been reported in The Annals of Pharmacotherapy.

An otherwise healthy 55-year-old woman was prescribed rabeprazole 20 mg/day administered in the morning for persistent symptoms of dyspepsia. Ten days later, she presented with a 7 day history of marked anxiety associated with panic attacks, night terror (pavor nocturnus), episodic mental confusion, and attention deficit. Within 2 days of discontinuing rabeprazole, the patient recovered completely from the neuropsychiatric manifestations. Subsequent esomeprazole therapy did not cause psychiatric symptoms.

Source: http://www.theannals.com/cgi/content/abstract/41/7/1315

Elevation of LDL cholesterol concentration with Over the Counter Fish oil preparation

A case of elevated low-density lipoprotein cholesterol (LDL-C) concentration in a patient taking fish oil supplements for hypertriglyceridemia has been reported in the Annals of Pharmacotherapy.

A 63-year-old white woman had been taking 2.7 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) daily in 9 g of over-the-counter (OTC) fish oil capsules for triglyceride lowering. Prior to the adverse event, she had baseline fasting triglyceride (TG) and LDL-C concentrations of 278 mg/dL and 106 mg/dL, respectively. After 6 weeks of treatment with fish oil, fasting TG levels decreased by 47.5% (-132 mg/dL) and the LDL-C increased by 75% (+80 mg/dL). Discontinuation of therapy for 6 weeks resulted in TG returning to high concentrations (334 mg/dL; +56 mg/dL change from baseline) and LDL-C decreasing toward baseline (143 mg/dL; +37 mg/dL change from baseline).

This case documents a much higher LDL-C elevation associated with OTC fish oil supplementation than has been previously identified in the literature. Healthcare providers should be advised that LDL-C levels may increase with use of OTC fish oil and should monitor patients periodically for such elevations. The significance of this increase on clinical outcomes is not known.

Source: http://www.theannals.com/cgi/content/abstract/41/7/1296

China stops sale of Methotrexate

China's drug safety agency has suspended sales of Methotrexate, a drug used to treat acute leukemia and rheumatoid arthritis.

Sales of methotrexate produced by Shanghai Hualian Pharmaceutical Co. Ltd. have been suspended because it caused an adverse reaction in several child leukemia patients in three hospitals in Shanghai and the southern province of Guangxi.

Some children felt pain in their legs while others experienced difficulty in walking after being injected with methotrexate numbered 070403A and 070403B.

Source: Reuters

http://www.reuters.com/article/healthNews/idUSPEK1476920070707

Ceftriaxone Sodium

Roche and FDA informed healthcare professionals of revisions to the CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION sections of the prescribing information for Rocephin for Injection. The revisions are based on new information that describes the potential risk associated with concomitant use of Rocephin with calcium or calcium containing solutions or products. Cases of fatal reactions with calcium-ceftriaxone precipitates in the lungs and kidneys in both term and premature neonates were reported. Hyperbilirubinemic neonates, especially prematures, should not be treated with Rocephin. The drug must not be mixed or administered simultaneously with calcium-containing solutions or products, even via different infusion lines. Additionally, calcium-containing solutions or products must not be administered within 48-hours of the last administration of ceftriaxone.

Source: FDA MedWatch July 5th 2007.

http://www.fda.gov/medwatch/safety/2007/safety07.htm#Rocephin

Unusual side effects with Acamprosate

A case report of a subject reporting with Extra Pyramidal Symptoms after adminstration of Acamprosate for treatment of Alcohol dependence has been reported.

Source: Indian J Psychiatry 2007;49:143.

http://www.indianjpsychiatry.org/article.asp?issn=0019-5545;year=2007;volume=49;issue=2;spage=143;epage=143;aulast=Sidana

Escitalopram induced Mania

A report of a case of recurrent depression with hypertension, ischemic heart disease and diabetes mellitus which switched to mania while on escitalopram. Escitalopram, one of the newer selective serotonin reuptake inhibitors (SSRIs), is considered to have fewer adverse effects and a lower propensity for drug interactions. However, escitalopram may induce mania at a maximum dose of 20 mg especially when given with Alprazolam which is known to boost efficacy of SSRIs.

Source: Indian J Psychiatry 2007;49:121-122.

http://www.indianjpsychiatry.org/article.asp?issn=0019-5545;year=2007;volume=49;issue=2;spage=121;epage=122;aulast=Parker

Sanofi-Aventis Withdraws New Drug Application for Rimonabant

Sanofi-aventis announced it would withdraw its new drug application for Zimulti (Rimonabant) after an FDA advisory committee recommended against approving the drug over concerns it increased the risk of suicide.

The agency’s Endocrinological and Metabolic Drugs Advisory Committee voted unanimously that available safety data was insufficient to evaluate Zimulti’s (rimonabant) risk profile. The committee held the meeting over concerns of potential safety signals for psychiatric adverse events and suicidality.

Sanofi-aventis also said it plans to submit an update of rimonabant’s safety data to the European Medicine’s Agency (EMEA) Committee for Medicinal Products for Human Use. The agency announced it will review data on psychiatric events as part of its continuous monitoring of the drug’s safety. The EMEA announced it would re-examine the drug after the FDA advisory committee voted against its approval.

Source: American College of Clinical Pharmacology eNews group dated 3rd July 2007.

Piroxicam

The European Medicines Agency (EMEA) has recommended restrictions on the use of piroxicam containing medicinal products because of the risk of gastrointestinal side effects and serious skin reactions.

The Agency’s Committee for Medicinal Products for Human Use (CHMP) concluded that piroxicam should no longer be used for treatment of short-term painful and inflammatory conditions. Piroxicam can still be prescribed for the symptomatic relief of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. However it should not be the first choice of non-steroidal anti-inflammatory drug (NSAID) treatment in these conditions.

Prescription of piroxicam should always be initiated by a physician experienced in the treatment of patients with inflammatory or degenerative rheumatic diseases and treatment should be used in the lowest dose (no more than 20 mg per day) and for the shortest duration possible. In any case, the treatment should be reviewed after the first 14 days of starting.

Source: EMEA Press release: http://www.emea.europa.eu/pdfs/human/press/pr/26514407en.pdf

Omalizumab

Genetech and FDA informed healthcare professionals and asthmatic patients that the prescribing information for Xolair (Omalizumab) was revised to include a new BOXED WARNING, and updated WARNINGS, PRECAUTIONS, and ADVERSE REACTIONS sections that address the risk of anaphylaxis (the onset of action can be delayed for 24 hours or more) when taking this medication. In addition, a new MEDICATION GUIDE was developed and will be provided to patients when a prescription for Xolair is filled or refilled at the pharmacy. Due to the risk of anaphylaxis, Xolair should only be administered to patients in a healthcare setting under direct medical supervision. Patients should be observed for an appropriate period of time following each Xolair injection.

Source: FDA MedWatch http://www.fda.gov/medwatch/safety/2007/safety07.htm#Xolair

Hypopigmentation associated with Imatinib Mesylate

Three cases of hypopigmentation in patients of CML (Chronic Myelogenous Leukemia) being treated with Imatinib have been reported in Journal of Association of Physicians of India JAPI.

Source and Detailed Report: JAPI 2007;55:527.

http://www.japi.org/july2007/Corr1.pdf

Colistimethate

FDA notified healthcare professionals and cystic fibrosis patients that the Agency is investigating the possible connection between the use of a liquid solution of Colistimethate that was premixed for inhalation with a nebulizer and the death of a patient with cystic fibrosis (CF). Colistimethate is FDA approved for intravenous or intramuscular injection for the treatment of acute or chronic infections due to sensitive strains of certain Gram-negative bacilli, particularly sensitive strains of Pseudomonas aeruginosa which are a significant problem for patients with CF and for patients with neutropenia, and/or immune system compromise. The product is not FDA approved for use as a liquid to be inhaled via nebulizer. In this case, the drug was prepared by a pharmacy and dispensed as prescribed in premixed unit dose ready-to-use vials. Once Colistimethate is mixed into a liquid form, the product breaks down into other chemicals that can damage lung tissue.

Healthcare professionals who choose to prescribe Colistimethate to treat patients with CF should be aware of the potential for serious and life threatening side effects from inhalation of pre-mixed, ready-to-use liquid forms of the product. Patients should discard any unused pre-mixed liquid forms of Colistimethate.

Source: FDA Medwatch
http://www.fda.gov/cder/drug/InfoSheets/HCP/colistimethateHCP.htm

Propofol

FDA informed healthcare professionals about several clusters of patients who experienced chills, fever, and body aches shortly after receiving propofol for sedation or general anesthesia. Multiple vials and several lots of propofol used in patients who experienced these symptoms were tested and there was no evidence that the propofol vials or prefilled syringes used were contaminated with bacteria or endotoxins. Propofol is an intravenous sedative-hypnotic agent for use in the induction and maintenance of anesthesia or sedation.

To minimize the potential for bacterial contamination, propofol vials and prefilled syringes should be used within six hours of opening and one vial should be used for one patient only. Patients who develop fever, chills, body aches or other symptoms of acute febrile reactions shortly after receiving propofol should be evaluated for bacterial sepsis. Healthcare professionals who administer propofol for sedation or general anesthesia should carefully follow the recommendations for handling and use in the product's full prescribing information.

Source: FDA Medwatch
http://www.fda.gov/cder/drug/infopage/propofol/default.htm

FDA Updates RotaTeq Label

The FDA has added information about Kawasaki disease to the label for the rotavirus vaccine (RotaTeq), but has not issued new warnings or precautions about the vaccine's use and maintains that it is safe.

The updated label includes information about six cases of Kawasaki disease that occurred during the drug's clinical trials and three cases reported since the vaccine was licensed in February 2006. The number of cases reported is no greater than the number that would be expected by chance. There is no known cause-and-effect relationship between the vaccine and the disease.

The FDA will monitor for additional cases of Kawasaki disease, but says that the vaccine is safe and effective and the "best way to protect a child against rotavirus disease."

Source: Physician's First Watch June 18th 2007

Detailed FDA report: http://www.fda.gov/cber/label/rotateqLBinfo.htm

FDA Advisory Panel Rejects Obesity Drug

An FDA advisory panel has voted unanimously not to recommend sale in the U.S. of rimonabant, a widely anticipated antiobesity drug, the New York Times reports.
The drug, available in 37 countries, was rejected "because of worries that it causes neurological and psychiatric problems and increases the risk of suicide," according to the newspaper.
Rimonabant is a cannabinoid-receptor blocker. In clinical studies, it had shown favorable effects not only on weight loss but also on fasting glucose, HDL cholesterol, and triglycerides.

Source: Physician’s First Watch June 15th 2007

Link: http://www.nytimes.com/2007/06/14/business/14drugs.html?ex=1182657600&en=1879e8c6b01830c7&ei=5070

Indian Drug Regulator to investigate Glitazones

The Indian drug regulator (Drug Controller General of India DCGI) will now investigate safety concerns on Avandia and Actos, two key diabetes medicines that could potentially be affecting 10 million diabetics in India.

The move follows the US Food and Drug Administration (FDA) directive putting both the drugs, Rosiglitazone and Pioglitazone, under the strictest drug safety warnings (Black Box) following the publication of recent studies linking them to an increased risk of heart failures.

Versions of Avandia are being sold by Indian companies such as Sun Pharmaceuticals Ltd, Cipla Ltd, Glenmark Pharmaceuticals Ltd and Torrent Pharmaceuticals Ltd, besides Glaxo’s GSK Pharmaceuticals Ltd unit.

Source: http://www.livemint.com/2007/06/08002046/DrugregulatorasksGSK-for-Av.html

FDA Asks for Black-Box Warning on Heart Failure Risk with Thiazolidinediones

The US FDA commissioner revealed that the agency has requested the manufacturers of rosiglitazone (Avandia) and pioglitazone (Actos) to add black-box warnings about the risk for heart failure with these drugs.

The FDA indicated that the request was made because although the drugs currently carry warnings about potential heart failure, they are still sometimes being prescribed to patients with this condition thus creating a need for stricter action.

Reference: New York Times dated 7th June 2007

http://www.nytimes.com/2007/06/07/health/07drug.html?_r=1&hp=&adxnnl=1&oref=slogin&adxnnlx=1181219366-DOm2snpHxZbSZJFCCGfiqw

Interstitial Nephritis Associated with Omeprazole

Case
A 62-year-old man presented with acute renal failure. On examination, there were no allergic features such as rash, fever or eosinophilia. Urine examination was normal. Previous renal function was normal. His creatinine peaked at 470 micromol/L. Investigations included tests for anti-neutrophil cytoplasmic and antinuclear antibodies, antibodies against extractable nuclear antigens, double-stranded DNA, complement, hepatitis serology, serum paraprotein concentration and renal ultrasound, all of which were normal. Renal biopsy showed florid interstitial nephritis.

A few weeks earlier, he was diagnosed with Helicobacter gastritis and treated with triple therapy (omeprazole, amoxycillin, clarithromycin) followed by omeprazole 40 mg daily. He had previously been taking pantoprazole for dyspepsia. Other medical history included a knee injury six months earlier. This had been treated with diclofenac, which was associated with the development of a rash and was substituted with rofecoxib. The exact duration of treatment with rofecoxib was unclear.

Omeprazole was changed to ranitidine and the man was treated with tapering doses of prednisolone, commencing at 75 mg daily. On examination three years later, his creatinine had improved to 123 micromol/L.

Comment
Acute interstitial nephritis is due to a hypersensitivity reaction and is typically associated with reversible acute renal failure. Drugs account for 71% of cases of acute interstitial nephritis.Medicines commonly implicated include non-steroidal anti-inflammatory drugs (NSAIDs), penicillins, cephalosporins, sulfonamides and proton pump inhibitors. Drug-induced interstitial nephritis is not dose dependent and can recur with rechallenge. The classic triad for interstitial nephritis of fever, rash and eosinophilia occurs in less than 10% of cases.Urine examination including microscopy may show haematuria, proteinuria, white cells, casts and eosinophiluria, but may be unremarkable.

Interstitial nephritis may occur with all of the proton pump inhibitors, although most reports to the Australian Adverse Drug Reactions Advisory Committee (ADRAC) have been with omeprazole.To date (14 May 2007) ADRAC have 82 reports associated with proton pump inhibitors. Of these cases, 50 were associated with omeprazole, 12 with esomeprazole, 6 with pantoprazole and 14 with rabeprazole. The duration of proton pump inhibitor treatment before presentation is usually between two weeks and nine months.

The temporal relationship in this case suggests that omeprazole was the most likely cause of interstitial nephritis, although the possibility that amoxycillin, pantoprazole or the NSAID were implicated cannot be excluded.

For more detailed information refer to the source article
Interstitial Nephritis Associated with Omeprazole (Aust Prescr 2007;30:67)

http://www.australianprescriber.com/magazine/30/3/artid/884/

FDA Warns on Chinese-Manufactured Toothpaste

The FDA is warning consumers to throw out any Chinese toothpaste after it found a component of antifreeze in several products.

Because diethylene glycol (DEG) is not always listed in the ingredients on the package, the FDA says people should examine their toothpaste and discard any imported from China. So far there have been no reports of injuries from DEG-contaminated toothpaste, but there have been deaths in several countries from DEG-contaminated products like cough syrup. The FDA is concerned about chronic exposure to DEG, particularly to vulnerable populations like children and people with kidney or liver disease.

Source: Physician's First Watch June 4 2007

Reference: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01646.html

Rosiglitazone

FDA News

FOR IMMEDIATE RELEASE
P07-88
May 21, 2007

Media Inquiries:Susan Cruzan, 301-827-6242
Consumer Inquiries:888-INFO-FDA

FDA Issues Safety Alert on Avandia

The U.S. Food and Drug Administration (FDA) is aware of a potentialsafety issue related to Avandia (rosiglitazone) , a drug approved totreat type 2 diabetes. Safety data from controlled clinical trialshave shown that there is a potentially significant increase in therisk of heart attack and heart-related deaths in patients takingAvandia. However, other published and unpublished data from long-termclinical trials of Avandia, including an interim analysis of data fromthe RECORD trial (a large, ongoing, randomized open label trial) andunpublished reanalyses of data from DREAM (a previously conductedplacebo-controlled, randomized trial) provide contradictory evidenceabout the risks in patients treated with Avandia.

Patients who are taking Avandia, especially those who are known tohave underlying heart disease or who are at high risk of heart attackshould talk to their doctor about this new information as theyevaluate the available treatment options for their type 2 diabetes.

FDA's analyses of all available data are ongoing. FDA has notconfirmed the clinical significance of the reported increased risk inthe context of other studies. Pending questions include whether theother approved treatment from the same class of drugs, pioglitazone,has less, the same or greater risks. Furthermore, there is inherentrisk associated with switching patients with diabetes from onetreatment to another even in the absence of specific risks associatedwith particular treatments. For these reasons, FDA is not askingGlaxoSmithKline, the drug's sponsor, to take any specific action atthis time. FDA is providing this emerging information to prescribersso that they, and their patients, can make individualized treatmentdecisions.

"FDA remains committed to assuring that doctors and patients have thelatest information available to make treatment and medication usedecisions. In this case, FDA is carefully weighing several complexsources of data, some of which show conflicting results, related tothe risk of heart attack and heart-related deaths in patients treatedwith Avandia," said Steven Galson, M.D., M.P.H., director of FDA'sCenter for Drug Evaluation and Research. "We will complete ouranalyses and make the results available as soon as possible. FDA willtake the issue of cardiovascular risk associated with Avandia andother drugs in this class to an Advisory Committee as soon as one canbe convened."

Avandia was approved in 1999 for treatment of type 2 diabetes, aserious and life threatening disease that affects about 18 to 20million Americans. Diabetes is a leading cause of coronary heartdisease, blindness, kidney failure and limb amputation. Since the drugwas approved, FDA has been monitoring several heart-related adverseevents (e.g., fluid retention, edema and congestive heart failure)based on signals seen in previous controlled clinical trials ofAvandia alone and in combination with other drugs, and frompostmarketing reports. FDA has updated the product's labeling onseveral occasions to reflect these new data, most recently in 2006.The most recent labeling change for Avandia also included a newwarning about a potential increase in heart attacks and heart-relatedchest pain in some individuals using Avandia. This new warning wasbased on the result of a controlled clinical trial in patients withexisting congestive heart failure.

Recently, the manufacturer of Avandia provided FDA with a pooledanalysis (meta analysis) of 42 randomized, controlled clinical trialsin which Avandia was compared to either placebo or other anti-diabetictherapies in patients with type 2 diabetes. The pooled analysissuggested that patients receiving short-term (most studies were6-months duration) treatment with Avandia may have a 30-40 percentgreater risk of heart attack and other heart-related adverse eventsthan patients treated with placebo or other anti-diabetic therapy.These data, if confirmed, would be of significant concern sincepatients with diabetes are already at an increased risk of heart disease.

Avandia is manufactured by GlaxoSmithKline, which is based in ResearchTriangle Park, N.C.

Source: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01636.html