FDA Patient Safety News: Show #85, April 2009

Stronger Warnings for Bowel Cleansing Agents

FDA is announcing new safety measures for oral sodium phosphate (OSP) products used for bowel cleansing before colonoscopies and other procedures. These products are associated with acute phosphate nephropathy, a rare but serious type of kidney injury. The events have been reported with the prescription products Visicol and OsmoPrep, and also over-the-counter sodium phosphate products when they are used as bowel cleansers.

FDA first warned about this problem in 2006, but cases of kidney injury continue to be reported. So FDA is requiring the manufacturer of Visicol and OsmoPrep to take several steps. First, a boxed warning about the risk of acute phosphate nephropathy will be added to the product label. The manufacturer will also conduct a new clinical trial to further study the risk of acute kidney injury with these products, provide a Medication Guide for patients, and implement a risk evaluation and mitigation strategy to ensure that the benefits of using these products outweigh their risks.

FDA believes that oral sodium phosphate products should be available only by prescription when they are used for bowel cleansing. Because of this, C.B. Fleet Company has voluntarily recalled the company's oral sodium phosphate products sold over the counter, (Fleet Phospho-soda and Fleet EZ-PREP) and has advised healthcare professionals not to instruct patients to use these products for bowel cleansing. Unico Holdings, Inc. is also recalling its OTC oral sodium phosphate products sold for bowel cleansing.

Health professionals should use caution when prescribing Visicol or OsmoPrep for patients who may be at higher risk of kidney injury. This includes those over aged 55, or those who have kidney disease, bowel obstruction, active colitis, or are dehydrated. It also includes patients taking drugs that affect renal perfusion or function such as diuretics, ACE inhibitors, angiotensin receptor blockers (ARBs) and possibly NSAIDS.

Prescribers should instruct patients about how to prepare for their procedures, and tell them to avoid dehydration by drinking enough clear liquids before, during and after bowel preparation. They should also tell patients to be alert for symptoms of acute kidney injury, including malaise, lethargy, drowsiness, decreased urine volume and swelling of the ankles, feet and legs.

Additional Information:

FDA MedWatch Safety Alert. Oral Sodium Phosphate (OSP) Products for Bowel Cleansing (marketed as Visicol and OsmoPrep, and oral sodium phosphate products available without a prescription). December 11, 2008.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm094900.htm


Stronger Warnings for Bowel Cleansing Agents

FDA is announcing new safety measures for oral sodium phosphate (OSP) products used for bowel cleansing before colonoscopies and other procedures. These products are associated with acute phosphate nephropathy, a rare but serious type of kidney injury. The events have been reported with the prescription products Visicol and OsmoPrep, and also over-the-counter sodium phosphate products when they are used as bowel cleansers.

FDA first warned about this problem in 2006, but cases of kidney injury continue to be reported. So FDA is requiring the manufacturer of Visicol and OsmoPrep to take several steps. First, a boxed warning about the risk of acute phosphate nephropathy will be added to the product label. The manufacturer will also conduct a new clinical trial to further study the risk of acute kidney injury with these products, provide a Medication Guide for patients, and implement a risk evaluation and mitigation strategy to ensure that the benefits of using these products outweigh their risks.

FDA believes that oral sodium phosphate products should be available only by prescription when they are used for bowel cleansing. Because of this, C.B. Fleet Company has voluntarily recalled the company's oral sodium phosphate products sold over the counter, (Fleet Phospho-soda and Fleet EZ-PREP) and has advised healthcare professionals not to instruct patients to use these products for bowel cleansing. Unico Holdings, Inc. is also recalling its OTC oral sodium phosphate products sold for bowel cleansing.

Health professionals should use caution when prescribing Visicol or OsmoPrep for patients who may be at higher risk of kidney injury. This includes those over aged 55, or those who have kidney disease, bowel obstruction, active colitis, or are dehydrated. It also includes patients taking drugs that affect renal perfusion or function such as diuretics, ACE inhibitors, angiotensin receptor blockers (ARBs) and possibly NSAIDS.

Prescribers should instruct patients about how to prepare for their procedures, and tell them to avoid dehydration by drinking enough clear liquids before, during and after bowel preparation. They should also tell patients to be alert for symptoms of acute kidney injury, including malaise, lethargy, drowsiness, decreased urine volume and swelling of the ankles, feet and legs.

Additional Information:

C.B. Fleet Company Press Release. C.B. Fleet Voluntarily Recalls its Fleet Phospho-soda Product after FDA Safety Alert. December 11, 2008.
http://www.cbfleet.com/newsstory.php?id=8


Warning on Dietary Supplement “Venom Hyperdrive 3.0”

FDA is warning consumers not to take the dietary supplement "Venom Hyperdrive 3.0," which has been promoted for weight loss. This product has been found to contain sibutramine, a prescription drug used as an appetite suppressant under medical supervision. Sibutramine can increase blood pressure and heart rate, and may pose a significant risk for people with a history of heart disease, heart failure, arrhythmias or stroke. It also has the potential for abuse or addiction.

Venom Hyperdrive 3.0 is marketed by Applied Lifescience Research Industries. The product was sold via distributors and in retail stores nationwide, and also in a number of other countries. It was packaged in red plastic bottles containing 90 capsules each. The company recalled the product after the FDA's laboratory analysis showed that samples contained sibutramine in significant amounts.

Consumers who have this product should stop taking it immediately and contact their health care professional if they have experienced any adverse effects.

Additional Information:

FDA MedWatch Safety Alert. Venom HYPERDRIVE 3.0. January 27, 2009.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm092095.htm


Ethex Corp. Expands Recall of Generic Drugs and Supplements

UPDATE: The FDA announced a Consent Decree of permanent injunction enjoining KV Pharmaceutical Company, its subsidiaries Ethex Corporation and Ther-Rx Corporation, and its principal officers. The injunction will prevent the companies from manufacturing and shipping drugs until the firm obtains FDA approval.

The generic drug company Ethex Corporation is expanding earlier recalls to now include over 60 generic drug products, including narcotics and cardiac medications, as well as several dozen prescription prenatal vitamins and iron supplements. The company is taking this action as a precautionary measure because these products may have been manufactured under conditions that didn't comply with current Good Manufacturing Practices. Certain lots of some of these products were recalled earlier because of defects such as oversized tablets.

The additional products are being removed to assure that no other defective products remain in the marketplace. Most of them are recalled at the wholesale level, while a few are recalled to the retail pharmacy level. The complete list of affected products can be found below.

Patients who may have these products should continue to take them according to their prescriptions, because if they suddenly stop taking needed medication, it may put them at risk. Patients should contact their healthcare provider if they experience any problems that may be related to these products, or, if necessary, to obtain replacement prescriptions. For more information contact Ethex Customer Service at 1-800-748-1472.

Additional Information:

FDA Press Release. FDA Takes Action Against KV Pharmaceutical Company. March 2, 2009.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149535.htm


Ethex Corp. Expands Recall of Generic Drugs and Supplements

UPDATE: The FDA announced a Consent Decree of permanent injunction enjoining KV Pharmaceutical Company, its subsidiaries Ethex Corporation and Ther-Rx Corporation, and its principal officers. The injunction will prevent the companies from manufacturing and shipping drugs until the firm obtains FDA approval.

The generic drug company Ethex Corporation is expanding earlier recalls to now include over 60 generic drug products, including narcotics and cardiac medications, as well as several dozen prescription prenatal vitamins and iron supplements. The company is taking this action as a precautionary measure because these products may have been manufactured under conditions that didn't comply with current Good Manufacturing Practices. Certain lots of some of these products were recalled earlier because of defects such as oversized tablets.

The additional products are being removed to assure that no other defective products remain in the marketplace. Most of them are recalled at the wholesale level, while a few are recalled to the retail pharmacy level. The complete list of affected products can be found below.

Patients who may have these products should continue to take them according to their prescriptions, because if they suddenly stop taking needed medication, it may put them at risk. Patients should contact their healthcare provider if they experience any problems that may be related to these products, or, if necessary, to obtain replacement prescriptions. For more information contact Ethex Customer Service at 1-800-748-1472.

Additional Information:

FDA MedWatch Safety Alert. Ethex Corporation Product Recall. February 4, 2009.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm092072.htm


Ethex Corp. Expands Recall of Generic Drugs and Supplements

UPDATE: The FDA announced a Consent Decree of permanent injunction enjoining KV Pharmaceutical Company, its subsidiaries Ethex Corporation and Ther-Rx Corporation, and its principal officers. The injunction will prevent the companies from manufacturing and shipping drugs until the firm obtains FDA approval.

The generic drug company Ethex Corporation is expanding earlier recalls to now include over 60 generic drug products, including narcotics and cardiac medications, as well as several dozen prescription prenatal vitamins and iron supplements. The company is taking this action as a precautionary measure because these products may have been manufactured under conditions that didn't comply with current Good Manufacturing Practices. Certain lots of some of these products were recalled earlier because of defects such as oversized tablets.

The additional products are being removed to assure that no other defective products remain in the marketplace. Most of them are recalled at the wholesale level, while a few are recalled to the retail pharmacy level. The complete list of affected products can be found below.

Patients who may have these products should continue to take them according to their prescriptions, because if they suddenly stop taking needed medication, it may put them at risk. Patients should contact their healthcare provider if they experience any problems that may be related to these products, or, if necessary, to obtain replacement prescriptions. For more information contact Ethex Customer Service at 1-800-748-1472.

Additional Information:

KV Pharma Press Release. ETHEX Corporation Issues Nationwide Voluntary Recall of Products. January 28, 2009.
http://www.ethex.com/news/pressRelease012809.aspx


Avoiding Medication Errors with Multiple Brand Names

The Institute for Safe Medication Practices (ISMP) recently highlighted medication errors that can occur when a drug is marketed under more than one brand name, especially when one of those names is well established.

ISMP describes a case where a female patient went to the emergency department with ischemic chest pain and ECG changes. One of her medications was Revatio, which had been prescribed to treat her pulmonary arterial hypertension. The ED physician reviewed the patient's medication list but did not recognize that Revatio contains sildenafil, the active ingredient in Viagra. The patient was given aspirin and sublingual nitroglycerin, and later was started on an IV nitroglycerin infusion for continued chest pain and elevated troponin-T.

Using organic nitrates in any form, at any time, with sildenafil and similar erectile dysfunction drugs is contraindicated. Fortunately, this patient did not experience adverse effects or blood pressure changes because an internist quickly recognized the problem and stopped the infusion.

ISMP cites other cases where patients received duplicate therapy after taking the same medication prescribed or dispensed under two trade names. These errors have occurred with bupropion (sold as both ZYBAN and WELLBUTRIN), finasteride (sold as PROPECIA and PROSCAR), and fluoxetine (sold as SARAFEM and PROZAC). ISMP says that this type of error may be more likely when the same drug is dispensed from two pharmacies under two different brand names. It is also more likely to happen when a physician prescribes the product by its generic name, but it's dispensed and labeled by its brand name, or when generic products are available under different brand names.

ISMP says that health professionals can reduce the risk of errors by conducting a thorough drug history and reviewing drug information if they encounter unfamiliar product names. ISMP also suggests that health professionals encourage patients to fill their prescriptions at the same pharmacy where possible, to help avoid taking the same product under different names.

Additional Information:

ISMP Medication Safety Alert! Revatio=sildenafil=Viagra. January 29, 2009.
http://www.ismp.org/Newsletters/acutecare/articles/20090129.asp


Preventing Misconnection Errors – Medical Device Safety Calendar

FDA has received many reports of patient injuries and deaths when different device delivery systems are mistakenly connected to each other. These errors are often facilitated by fittings called Luer connectors, which allow different systems to be easily, but erroneously, connected.

The 2009 Medical Device Safety Calendar is one of FDA's efforts to help educate healthcare professionals about these dangerous misconnections. The calendar provides a graphic depiction of a variety of misconnection cases, coupled with recommendations from The Joint Commission on ways to prevent these types of errors. We hope the calendar will be posted as a year-long reminder to staff that these errors can occur in any clinical setting. We also urge clinicians to use the case synopses and recommendations as on-going training materials. They can be downloaded free of charge by going to the website. Clinical facilities may also request copies of the calendar while supplies last.

Additional Information:

FDA Center for Devices and Radiological Health Luer Misconnections website.
http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/UCM134863


Confusing Heparin Labels Can Lead to Errors

The Institute for Safe Medication Practices (ISMP) points out that some multiple dose heparin vials have potentially confusing labels that could lead to dangerous overdoses. These vials, which contain 4 mL of heparin solution, are labeled "10,000 USP units/ 1 mL," with the "10,000" in larger print than the rest of the designation. Because of this, someone quickly reading the label could assume that the entire vial contains 10,000 units. Calculating the patient's dose based on that mis-reading of the label could result in a fourfold overdose.

To help avoid this potential hazard, ISMP suggests that hospitals consider whether they need heparin in vials that contain more than 10,000 units per vial.

Additional Information:

ISMP Medication Safety Alert! Is It Really Needed? January 15, 2009.
http://www.ismp.org/Newsletters/acutecare/articles/20090115-1.asp


Preventing Overdoses when Using Methadone to Treat Chronic Pain

A report from the Institute for Safe Medication Practices lists several reasons for the serious and sometime fatal overdoses that have occurred when methadone is used to treat moderate to severe chronic pain.

ISMP points out that methadone differs from other opioids in a number of ways. For example, methadone remains in the body long after its analgesic effect has worn off. Also, a patient may not experience the full analgesic effect of methadone until 3-5 days of use, so it must be titrated more slowly than other opioids.

And a high degree of tolerance to other opioids does not eliminate the possibility of methadone overdose. ISMP cites two fatalities and a near fatality from prescribing too large a methadone dose for patients who had previously taken high daily doses of Oxycontin or Vicodin. Also, if a patient on methadone stops taking the drug for three consecutive days, the patient may lose tolerance for methadone and be at risk for an overdose if the usual dose is resumed.

Errors have also been reported because of confusion between methadone and other drugs with "look alike" names. In one report, a 17-year old patient with a traumatic brain injury received 25 mg of methadone BID instead of methylphenidate and suffered respiratory arrest.

ISMP also points out that errors can occur because of confusion between mL and mg doses. In one case, a patient had been taking 13 mg/day of methadone, which was prepared in the community pharmacy using a 1 mg/mL methadone concentration. When the patient was hospitalized, the attending physician assumed that the hospital carried the same concentration and prescribed 12 mL of methadone without specifying the dose in mg. The order was filled with a stock solution that contained 10 mg/mL and administered to the patient --- an overdose of nearly tenfold. Fortunately the patient vomited most of the medication and survived.

ISMP recommends a number of steps to help prevent these kinds of life-threatening errors. Here are some of them:

• When prescribing methadone for pain, avoid concomitant use of other narcotics, benzodiazepines, and sedatives, because these significantly increase the risk of an adverse event. Prescribe oral liquid doses of methadone in mg, never in mL alone, since several concentrations exist. Include the indication for use when prescribing methadone, to avoid confusion with methylphenidate. Specify the exact time(s) for administration. If the daily dose is taken in the evening one day and then in the morning the next day, this could lead to an overdose.

• When dispensing methadone, use commercially available methadone solutions to prevent compounding errors. Stock only one concentration of oral liquid methadone in the pharmacy, if possible. Accept orders for methadone only when the dose is prescribed in mg. Label all unit-doses with the exact dose, including strength and total volume if it is a liquid, along with the date and time for administration.

• When administering methadone, adhere to standard medication administration times. If a dose is missed, check with the physician before administering it later than originally scheduled. Make sure a pharmacist has reviewed the order before giving the medication to the patient.

• Remind patients to take methadone exactly as prescribed. Instruct them not to start or stop taking any other medications or dietary supplements without talking to their prescriber, because methadone interacts with many other drugs.

• Instruct methadone patients to seek medical attention if they experience symptoms of overdose, such as slow or shallow breathing and extreme sleepiness, or symptoms of arrhythmia.

Additional Information:

ISMP Medication Safety Alert! Keeping Patients Safe from Iatrogenic Methadone Overdoses. February 14, 2008. Volume 13, Issue 3, Page 1-3.
http://www.ismp.org/newsletters/acutecare/articles/20080214.asp


Preventing Overdoses when Using Methadone to Treat Chronic Pain

A report from the Institute for Safe Medication Practices lists several reasons for the serious and sometime fatal overdoses that have occurred when methadone is used to treat moderate to severe chronic pain.

ISMP points out that methadone differs from other opioids in a number of ways. For example, methadone remains in the body long after its analgesic effect has worn off. Also, a patient may not experience the full analgesic effect of methadone until 3-5 days of use, so it must be titrated more slowly than other opioids.

And a high degree of tolerance to other opioids does not eliminate the possibility of methadone overdose. ISMP cites two fatalities and a near fatality from prescribing too large a methadone dose for patients who had previously taken high daily doses of Oxycontin or Vicodin. Also, if a patient on methadone stops taking the drug for three consecutive days, the patient may lose tolerance for methadone and be at risk for an overdose if the usual dose is resumed.

Errors have also been reported because of confusion between methadone and other drugs with "look alike" names. In one report, a 17-year old patient with a traumatic brain injury received 25 mg of methadone BID instead of methylphenidate and suffered respiratory arrest.

ISMP also points out that errors can occur because of confusion between mL and mg doses. In one case, a patient had been taking 13 mg/day of methadone, which was prepared in the community pharmacy using a 1 mg/mL methadone concentration. When the patient was hospitalized, the attending physician assumed that the hospital carried the same concentration and prescribed 12 mL of methadone without specifying the dose in mg. The order was filled with a stock solution that contained 10 mg/mL and administered to the patient --- an overdose of nearly tenfold. Fortunately the patient vomited most of the medication and survived.

ISMP recommends a number of steps to help prevent these kinds of life-threatening errors. Here are some of them:

• When prescribing methadone for pain, avoid concomitant use of other narcotics, benzodiazepines, and sedatives, because these significantly increase the risk of an adverse event. Prescribe oral liquid doses of methadone in mg, never in mL alone, since several concentrations exist. Include the indication for use when prescribing methadone, to avoid confusion with methylphenidate. Specify the exact time(s) for administration. If the daily dose is taken in the evening one day and then in the morning the next day, this could lead to an overdose.

• When dispensing methadone, use commercially available methadone solutions to prevent compounding errors. Stock only one concentration of oral liquid methadone in the pharmacy, if possible. Accept orders for methadone only when the dose is prescribed in mg. Label all unit-doses with the exact dose, including strength and total volume if it is a liquid, along with the date and time for administration.

• When administering methadone, adhere to standard medication administration times. If a dose is missed, check with the physician before administering it later than originally scheduled. Make sure a pharmacist has reviewed the order before giving the medication to the patient.

• Remind patients to take methadone exactly as prescribed. Instruct them not to start or stop taking any other medications or dietary supplements without talking to their prescriber, because methadone interacts with many other drugs.

• Instruct methadone patients to seek medical attention if they experience symptoms of overdose, such as slow or shallow breathing and extreme sleepiness, or symptoms of arrhythmia.

Additional Information:

FDA MedWatch Safety Alert. Dolophine (methadone hydrochloride). November 27, 2006.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm150642.htm



FDA Patient Safety News is available at www.fda.gov/psn