Ezetimibe/Simvastatin

FDA provided healthcare professionals with an early communication about an ongoing data review for Ezetimibe/Simvastatin (marketed as Vytorin), Ezetimibe (marketed as Zetia), and Simvastatin (marketed as Zocor).

This early communication is in keeping with FDA’s commitment to inform the public about ongoing postmarketing drug issues.Merck/Schering Plough Pharmaceuticals reported preliminary results from the Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia (ENHANCE) trial. This trial was designed to evaluate the amount of atherosclerotic plaque in blood vessels located in the neck based on images obtained through ultrasound in patients treated with Vytorin (ezetimibe plus simvastatin) or simvastatin alone. Merck/Schering Plough stated that there was no significant difference between Vytorin and simvastatin in the amount of atherosclerotic plaque in the inner walls of the carotid (neck) arteries despite greater lowering of LDL-cholesterol (bad cholesterol) with Vytorin compared to simvastatin. Once Merck/Schering Plough completes the analysis of the unblinded data from ENHANCE, it will submit a final study report to FDA. Once FDA receives the final study report, FDA estimates it will take approximately 6 months to fully evaluate the data. After reviewing the data from the ENHANCE study, and considering all other available information about the link between LDL lowering and reduction of cardiovascular events, FDA will determine whether any further regulatory action is warranted with regard to Zetia and Vytorin and also whether any changes to FDA’s current approach to drugs that lower LDL cholesterol are warranted.

Patients should talk to their doctors if they have any questions about the information from the ENHANCE trial.

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

Leukine (sargramostim)

Bayer and FDA informed healthcare professionals of the market withdrawal of the current liquid formulation of Leukine, a growth factor that helps fight infection and disease in appropriate patients by enhancing immune cell function. The product was withdrawn because of an upward trend in spontaneous reports of adverse reactions, including syncope (fainting), which are temporally correlated with a change in the formulation of liquid Leukine to include edetate disodium (EDTA). The upward trend in adverse reaction reporting rates has not been observed with the use of lyophilized Leukine. Healthcare professionals should immediately stop using liquid Leukine and return unused vials to the manufacturer.

Source: http://www.fda.gov/medwatch/safety/2008/Leukine_DHCP_01-23-2008.pdf

Heparin Sodium Injection 1000 units/mL recalled due to multiple adverse reactions

Baxter Healthcare and FDA notified healthcare professionals of a voluntary recall of certain lots of Heparin as a precaution due to an increase in reports of adverse patient reactions associated with these lots. Baxter is in the process of an in-depth investigation to determine the root cause of the reported reactions.

Reported adverse events include abdominal pain, decreased blood pressure, burning sensation, chest pain, diarrhea, dizziness, drug ineffectiveness, dyspepsia, dyspnea, erythema, flushing, headache, hyperhidrosis, hypoesthesia, hypotension, increased lacrimation, loss of consciousness, malaise, nausea, pallor, palpitations, paresthesia, pharyngeal edema, restlessness, vomiting/retching, stomach discomfort, tachycardia, thirst, trismus, and unresponsiveness to stimuli. There have been no reports involving fatality.

Source: http://www.fda.gov/medwatch/safety/2008/Heparin_recall_01-17-2008.pdf

Ortho Evra Contraceptive Transdermal Patch

FDA modified the prescribing information for the Ortho Evra Contraceptive Transdermal (Skin) Patch to include the results of a new epidemiology study that found that users of the birth control patch were at higher risk of developing serious blood clots, also known as venous thromboembolism (VTE), than women using birth control pills. VTE can lead to pulmonary embolism. The label changes are based on a study conducted by the Boston Collaborative Drug Surveillance Program on behalf of Johnson and Johnson. The patch was studied in women aged 15-44. These findings support an earlier study that also said women in this group were at higher risk for VTE.
FDA believes that Ortho Evra is a safe and effective method of contraception when used according to the labeling, which recommends that women with concerns or risk factors for serious blood clots talk with their health care provider about using Ortho Evra versus other contraceptive options.

Source: http://www.fda.gov/bbs/topics/NEWS/2008/NEW01781.html

Cough and Cold Medications in Children Less Than Two Years of Age

FDA informed consumers and healthcare professionals that the Agency has completed its review of information regarding the safety of over-the-counter (OTC) cough and cold medicines in children under 2 years of age and recommends that these drugs not be used to treat children in this age group because serious and potentially life-threatening side effects can occur. FDA's recommendation is based on both the review of the information the Agency received about serious side effects in children in the referenced age group and the discussion and recommendations made at the October 18 -19, 2007, public advisory committee meeting at which this issue was discussed. FDA has not completed its review of information about the safety of OTC cough and cold medicines in children 2 through 11 years of age.

Source: http://www.fda.gov/cder/drug/advisory/cough_cold_2008.htm

Edetate Disodium (marketed as Endrate and generic products)

FDA notified healthcare professionals and patients about important safety information concerning Edetate Disodium. There have been cases where children and adults have died when they were mistakenly given Edetate Disodium instead of Edetate Calcium Disodium (Calcium Disodium Versenate) or when Edetate Disodium was used for "chelation therapies" and other uses that are not approved by the FDA.

Edetate Disodium was approved as an emergency treatment for certain patients with hypercalcemia (very high levels of calcium in the blood) or certain patients with heart rhythm problems as a result of very high amounts of digitalis in the blood. Edetate Calcium Disodium was approved to reduce dangerously high blood lead levels (severe lead poisoning).

The two drugs have very similar names and are commonly referred to only as EDTA. As a result, the two products are easily mistaken for each other when prescribing, dispensing, and administering them. Edetate Disodium and Edetate Calcium Disodium works by binding with heavy metals or minerals in the body allowing them to be passed out of the body through the urine. Read the FDA Public Health Advisory for recommended and important safety considerations for healthcare professionals until the FDA's ongoing evaluation of the risks and benefits of Edetate Disodium is complete.

Source: http://www.fda.gov/cder/drug/advisory/edetate_disodium.htm

Musculoskeletal Pain Associated with Bisphosphonate use

FDA informed healthcare professionals and patients of the possibility of severe and sometimes incapacitating bone, joint, and/or muscle (musculoskeletal) pain in patients taking bisphosphonates.

Although severe musculoskeletal pain is included in the prescribing information for all bisphosphonates, the association between bisphosphonates and severe musculoskeletal pain may be overlooked by healthcare professionals, delaying diagnosis, prolonging pain and/or impairment, and necessitating the use of analgesics. The severe musculoskeletal pain may occur within days, months, or years after starting a bisphosphonates. Some patients have reported complete relief of symptoms after discontinuing the bisphosphonate, whereas others have reported slow or incomplete resolution. The risk factors for and incidence of severe musculoskeletal pain associated with bisphosphonates are unknown.

Healthcare professionals should consider whether bisphosphonate use might be responsible for severe musculoskeletal pain in patients who present with these symptoms and consider temporary or permanent discontinuation of the drug.

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

Methotrexate-Induced Papular Eruption Following Treatment of Psoriasis

A case of a 52-year-old woman presenting with an extensive flare of psoriasis associated with joint pain, especially in her knees and elbows on being treated with intramuscular injections of methotrexate 20 mg/wk has been published in the latest issue of The Annals of Pharmacotherapy.

According to the Naranjo probability scale, the papular eruption was probably caused by methotrexate. The drug was discontinued and papular lesions gradually disappeared.

Source: Annals of Pharmacotherapy 2007;42(1):138-141.

http://www.theannals.com/cgi/content/abstract/42/1/138

Simultaneous Erythema Nodosum and Erythema Multiforme After Local Lidocaine Injection

A case of a 33-year-old female experiencing coexisting erythema nodosum and erythema multiforme after lidocaine spray whichwas used for upper gastrointestinal endoscopy has been published in the latest issue of The Annals of Pharmacotherapy.

The reaction was exacerbated after localized injection of 2% lidocaine for a skin biopsy. An objective causality assessment revealed that an adverse drug reaction was highly probable.

Source: Annals of Pharmacotherapy 2007;42(1):127-130.

http://www.theannals.com/cgi/content/abstract/42/1/127

Clozapine-induced double incontinence

A case of clozapine-induced double incontinence in a 23 years old male diagnosed with schizophrenia and started on clozapine 25 mg/day has been reported in the latest isuue of Indian Journal of Medical Sciences.

On the Naranjo probability scale, the adverse drug reaction probability score for this patient to develop clozapine-induced double incontinence was nine, suggesting a definitive adverse reaction due to clozapine.

Source: Indian J Med Sci 2007;61:665-6

http://www.indianjmedsci.org/article.asp?issn=0019-5359;year=2007;volume=61;issue=12;spage=665;epage=666;aulast=Mendhekar