Olanzapine induced Tardive Dystonia

A case of a 32 years old male suffering from Olanzapine induced tardive dystonia has been reported in Indian Journal of Pharmacology.
Reference: Indian J Pharmacol 2008;40:237-8
Source: http://www.ijp-online.com/text.asp?2008/40/5/237/44158

Quetiapine induced myoclonus

Cases of 2 young females who developed myoclonic jerks while on quetiapine have been reported in Indian Journal of Medical Sciences.
Reference: Indian J Med Sci 2008;62:422-3
Source: http://www.indianjmedsci.org/text.asp?2008/62/10/422/44024

Paracetamol induced angioedema

A case of a 4-year-old boy with a presumed viral infection who developed allergic rash and angioedema probably related to paracetamol exposure.
Causality analysis (Naranjo's algorithm) gave a score of 6 (probable reaction).
Reference: Indian J Med Sci 2008;62:420-2
Source: http://www.indianjmedsci.org/article.asp?issn=0019-5359;year=2008;volume=62;issue=10;spage=420;epage=422;aulast=Panchabhai

Multifocal bullous fixed drug eruption due to fluconazole

A case of a 35-year-old female patient who presented with multifocal bullous FDE due to fluconazole has bee reported in the Indian Journal of Dermatology.

Reference- Indian J Dermatol 2008;53(3):156-157
Source: http://www.e-ijd.org/article.asp?issn=0019-5154;year=2008;volume=53;issue=3;spage=156;epage=157;aulast=Nath

Phenytoin and Fosphenytoin Sodium

FDA is investigating new preliminary data regarding a potential increased risk of serious skin reactions including Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) from phenytoin therapy in Asian patients positive for human leukocyte antigen (HLA) allele, HLA-B*1502. This allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including Han Chinese, Filipinos, Malaysians, South Asian Indians, and Thais. Until the FDA evaluation is completed, healthcare providers who are considering the use of phenytoin or fosphenytoin should be aware of the risks and benefits described in the current prescribing information for this drug. Healthcare providers should consider avoiding phenytoin and fosphenytoin as alternatives for carbamazepine in patients who test positive for HLA-B*1502.

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

Bisphosphonates and Atrial Fibrilation

FDA issued an update to the Agency's review of safety data regarding the potential increased risk of atrial fibrillation in patients treated with a bisphosphonate drug. 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, and to treat bone metastases and lower elevated levels of blood calcium in patients with cancer. FDA reviewed data on 19,687 bisphosphonate-treated patients and 18,358 placebo-treated patients who were followed for 6 months to 3 years. The occurrence of atrial fibrillation was rare within each study, with most studies containing 2 or fewer events. Across all studies, no clear association between overall bisphosphonate exposure and the rate of serious or non-serious atrial fibrillation was observed. Additionally, increasing dose or duration of bisphosphonate therapy was not associated with an increase rate of atrial fibrillation. Healthcare professionals should not alter their prescribing patterns for bisphosphonates and patients should not stop taking their bisphosphonate medication.

Source: http://www.fda.gov/cder/drug/early_comm/bisphosphonates_update_200811.htm

Efalizumab (Raptiva)

FDA notified healthcare professionals of extensive labeling changes, including a Boxed Warning, to highlight the risks of life-threatening infections, including bacterial sepsis, viral meningitis, invasive fungal disease, progressive multifocal leukoencephalopathy and other opportunistic infections with the use of Raptiva. In addition, the prescribing information will be updated to describe a potential risk for the permanent suppression of the immune system with repeat administration of Raptiva in children. Raptiva is not approved for children under 18 years of age. Doctors and other prescribers should carefully evaluate and weigh the risk/benefit profile of Raptiva for patients who would be more susceptible to these risks. Health care professionals should monitor patients treated with Raptiva for the signs and symptoms of these adverse events and also instruct patients to report any such signs and symptoms to them without delay. Patients identified to begin therapy with Raptiva should have received all their age-appropriate vaccinations before starting the drug.Patients with pre-existing infections or who have a compromised immune system should notify their health care professional before beginning treatment with Raptiva.
Source: http://www.fda.gov/bbs/topics/NEWS/2008/NEW01905.html

Over The Counter Cough and Cold Medications

FDA notified healthcare professionals and consumers that the Consumer Healthcare Products Association (CHPA) is voluntarily modifying the product labels for consumers of over the counter (OTC) cough and cold medicines to state "do not use" in children under 4 years of age. FDA supports CHPA members to help prevent and reduce misuse and to better inform consumers about the safe and effective use of these products for children. FDA continues to assess the safety and efficacy of these products and to revise its OTC list of approved ingredients and amounts for these medicines. Parents and care givers should adhere to the dosage instructions and warnings on the label that accompanies OTC cough and cold medications before giving the product to children, and should consult their healthcare professionals if they have any questions or concerns.
Source: http://www.fda.gov/bbs/topics/NEWS/2008/NEW01899.html

Statin drugs and amyotrophic lateral sclerosis (ALS)

An FDA analysis provides new evidence that the use of statins does not increase incidence of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease often referred to as "Lou Gehrig's Disease." The FDA analysis, undertaken after the agency received a higher than expected number of reports of ALS in patients on statins, is based on data from 41 long-term controlled clinical trials. The results showed no increased incidence of the disease in patients treated with a statin compared with placebo.The FDA is anticipating the completion of a case-control or epidemiological study of ALS and statin use. Results from this study should be available within 6-9 months. FDA is also examining the feasibility of conducting additional epidemiologic studies to examine the incidence and clinical course of ALS in patients taking statins. Based on currently available information, health care professionals should not change their prescribing practices for statins and patients should not change their use of statins.
Source: http://www.fda.gov/bbs/topics/NEWS/2008/NEW01892.html

Epoetin alfa

FDA has been made aware of preliminary safety findings from a clinical trial conducted in Germany investigating the use of epoetin alfa to treat acute ischemic stroke. The clinical trial utilized doses of epoetin alfa that were considerably higher than the doses recommended for the treatment of anemia as described in the FDA-approved labeling for the product. Over a period of ninety days after the start of the trial, there were more deaths in the group of patients who received epoetin alfa compared to patients who received the placebo (16% versus 9%). Roughly half of all deaths in both groups occurred within the first seven days after starting the drug, with death from intracranial hemorrhage (bleeding within the brain) occurring among approximately 4% of patients who received epoetin alfa compared to 1% of patients in the placebo group. FDA anticipates the receipt of additional data within the next several weeks. As soon as the review of these data is complete, FDA will communicate our conclusions and recommendations to the public. The finding of increased mortality in patients receiving epoetin alfa in the German trial suggests the need to closely monitor patients enrolled in other ongoing trials for adverse outcomes and to evaluate whether the potential benefits for enrolled patients outweigh the risks in these trials.
Source: http://www.fda.gov/cder/drug/early_comm/epoetin_alfa.htm

Erlotinib

OSI and Genentech notified healthcare professionals that cases of hepatic failure and hepatorenal syndrome, including fatalities, have been reported during use of Tarceva (Erlotinib), particularly in patients with baseline hepatic impairment. Patients with hepatic impairment receiving Tarceva should be closely monitored during therapy and the product should be used with extra caution in patients with total bilirubin >3x ULN. Dosing should be interrupted or discontinued if changes in liver function are severe, such as doubling of total bilirubin and/or tripling of transaminases in the setting of pretreatment values outside the normal range. New information from a pharmacokinetic study in patients with moderate hepatic impairment associated with significant liver tumor burden has been provided in the revised prescribing information, and other recommendations are included in the WARNINGS and DOSAGE AND ADMINISTRATION sections.

Source: http://www.fda.gov/medwatch/safety/2008/Tarceva_PI_DearHCPLetter.pdf

Rituximab

Genentech informed healthcare professionals of revisions to prescribing information for Rituxan regarding a case of progressive multifocal leukoencephalopathy (PML) leading to death in a patient with rheumatoid arthritis who received Rituxan in a long-term safety extension clinical study. The patient developed a JC virus infection with resultant PML and death 18 months after taking the last dose of Rituxan. Healthcare professionals treating patients with Rituxan should consider PML in any patient presenting with new onset neurologic manifestations. Additionally, consultation with a neurologist, brain MRI and lumbar puncture should be considered as clinically indicated.

Source: http://www.fda.gov/medwatch/safety/2008/rituxan_DHCP_Final%209411700.pdf

Tumor necrosis factor-alpha blockers (TNF blockers), Cimzia (certolizumab pegol), Enbrel (etanercept), Humira (adalimumab), and Remicade (infliximab)

FDA notified healthcare professionals that pulmonary and disseminated histoplasmosis, coccidioidomycosis, blastomycosis and other opportunistic infections are not consistently recognized in patients taking tumor necrosis factor-α blockers (TNF blockers). This has resulted in delays in appropriate treatment, sometimes resulting in death. For patients taking TNF blockers who present with signs and symptoms of possible systemic fungal infection, such as fever, malaise, weight loss, sweats, cough, dypsnea, and/or pulmonary infiltrates, or other serious systemic illness with or without concomitant shock, healthcare professionals should ascertain if patients live in or have traveled to areas of endemic mycoses. For patients at risk of histoplasmosis and other invasive fungal infections, clinicians should consider empiric antifungal treatment until the pathogen(s) are identified.

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

Natalizumab

FDA informed healthcare professionals of two new cases of progressive multifocal leukoencephalopathy (PML) in European patients receiving natalizumab monotherapy for multiple sclerosis for more than one year. PML, which is usually fatal, is a known risk of natalizumab treatment, but previous cases in patients with multiple sclerosis were seen in combination with other immunomodulatory therapies. Approximately 39,000 patients have received treatment with natalizumab worldwide, with approximately 12,000 patients receiving treatment for a least one year. No new cases have been seen in the US, where about 7,500 patients have received the drug for greater than one year and approximately 3,300 patients have received the drug for at least one and one-half years. In the U.S., natalizumab is available only to patients with relapsing multiple sclerosis or Crohn's disease who are enrolled in the risk minimization plan called the TOUCH Prescribing Program. Under this program, every natalizumab-treated patient is closely monitored and followed for the occurrence of PML and other serious opportunistic infections. While the two patients who developed PML were on monotherapy, the FDA still believes that natalizumab monotherapy may confer a lower risk of PML than when natalizumab is used together with other immunomodulatory medications. Prescribing information for natalizumab will be revised to include information informing prescribers and patients that cases of PML have occurred in patients taking natalizumab as monotherapy. Healthcare professionals should continue to monitor patients for sign and symptoms of PML. Additionally, natalizumab should not be infused if PML is suspected.

Source: http://www.fda.gov/cder/drug/InfoSheets/HCP/natalizumab2008HCP.htm

Ezetimibe/Simvastatin (marketed as Vytorin)

FDA informed healthcare professionals that the Agency is investigating a report from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of a possible association between the use of Vytorin and a potentially increased incidence of cancer. Vytorin is a combination product of simvastatin and ezetimibe used to decrease the production of cholesterol by the liver and inhibit the absorption of cholesterol in the intestine to reduce LDL-cholesterol levels and reduce the risk of cardiovascular events. Recently, FDA obtained preliminary results from the SEAS trial. The clinical trial tested whether lowering LDL-cholesterol with Vytorin would reduce the risk of cardiovascular events in individuals with aortic stenosis. A lower overall cardiovascular risk was not found with Vytorin. However, there was an additional observation that a larger percentage of subjects treated with Vytorin were diagnosed with and died from all types of cancer combined when compared to placebo during the 5-year study.
FDA anticipates receiving a final SEAS study report in about 3 months and the Agency's review and evaluation of the clinical trial data and other relevant information should take approximately 6 months. FDA will communicate its conclusions and recommendations at that time. Healthcare professionals and caregivers should continue to monitor patients taking Vytorin and report side effects from the use of this drug to the Agency.

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

Naltrexone

FDA informed healthcare professionals of the risk of adverse injection site reactions in patients receiving naltrexone. Naltrexone is indicated for the treatment of alcohol dependence in patients who are able to abstain from alcohol in an outpatient setting prior to initiation of treatment. Naltrexone is administered as an intramuscular gluteal injection and should not be administered intravenously, subcutaneously, or inadvertently into fatty tissue. Physicians should instruct patients to monitor the injection site and contact them if they develop pain, swelling, tenderness, induration, bruising, pruritus, or redness at the injection site that does not improve or worsens within two weeks. Physicians should promptly refer patients with worsening injection site reactions to a surgeon.

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

Simvastatin Used With Amiodarone

FDA notified healthcare professionals of the risk of muscle injury, rhabdomyolysis, which can lead to kidney failure or death, when simvastatin is used with amiodarone. This risk is dose-related and increases when a dose of simvastatin greater than 20 mg per day is given with amiodarone. Although a revision of the simvastatin labeling in 2002 described an increased risk of rhabdomyolysis when amiodarone is taken with simvastatin doses greater than 20 mg daily, FDA continues to receive reports of rhabdomyolysis in patients treated concurrently with amiodarone and simvastatin. Prescribers should be aware of the increased risk of rhabdomyolysis when simvastatin is prescribed with amiodarone, and they should avoid doses of simvastatin greater than 20 mg per day in patients taking amiodarone.

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

Erythropoiesis Stimulating Agents (ESAs)

FDA informed healthcare professionals of modifications to certain sections of the Boxed Warnings, Indications and Usage, and Dosage and Administration sections of prescribing information for Erythropoiesis Stimulating Agents (ESAs). The changes clarify the FDA-approved conditions for use of ESAs in patients with cancer and revise directions for dosing to state the hemoglobin level at which treatment with an ESA should be initiated. Additional revisions to prescribing information that ESAs are not intended for use in patients receiving myelosuppressive therapy when the expected outcome is cure and when to initiate and discontinue ESA dosing will be forthcoming. FDA continues to encourage healthcare professionals to discuss with their patients before starting or continuing therapy with ESAs, the benefits of treatment with ESAs and the potential and demonstrated risks of ESAs for thrombovascular events, shortened time to tumor progression or recurrence, and shortened survival time.

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