Health IT

Like many physicians, Larry Holder, MD, FACP, FHM, entered the medical profession with the desire to make a difference. After completing a fellowship in hematology and oncology in 1988, he joined Cancer Care Specialists of Central Illinois, a community oncology practice based in Decatur, and anticipated a lengthy career in which he would contribute to significant breakthroughs in cancer treatment.

After 12 years, however, he changed direction.

“I had become a bit disillusioned and realized we weren’t making big impacts, especially on the more common cancers,” he says. “I also got very attached to my patients, and in oncology, that’s not always a good thing. It became very trying emotionally.”

Dr. Holder spent the next five years practicing internal medicine at Community Health Improvement Center in Decatur. In 2005, he joined the hospitalist program at Decatur Memorial Hospital. Last year, he became medical director of hospitalist services, chief medical informatics officer (CMIO), and medical director of information systems.

Although he has found a new niche, his philosophy remains the same.

“Everything I do comes down to the fact I still love taking care of patients,” says Dr. Holder, one of six new members of Team Hospitalist. “That’s why I became a doctor. It’s very rewarding, and I never want to give that up.”

As a physician, I still find [clinical work] extremely rewarding. As medical director, I need to be in the trenches to know what the hospitalists are going through and what problems they are having. As CMIO, it’s very important that I use the system I’m in charge of trying to optimize.

Question: You left oncology partly because you became attached to your patients. Does that approach help you as a hospitalist?

Answer: Definitely. I try to teach younger hospitalists the value of developing a rapport with patients. I enjoy building that emotional or intellectual attachment. I’m a big believer in the human aspect of what we do, and it’s one of the aspects of my job I love the most.

Q: Did you join Decatur Memorial with aspirations of leading its hospitalist program?

A: No. My plan was to focus on giving good patient care, get involved on the quality side, and become the CMIO for the hospital. When the medical director role opened up, it seemed to be sitting there waiting to be filled. I structured it so I could continue to see patients and split my administrative time between being the medical director of the hospitalists and being the CMIO.

Q: Why is it so important for you to still see patients?

A: As a physician, I still find it extremely rewarding. As medical director, I need to be in the trenches to know what the hospitalists are going through and what problems they are having. As CMIO, it’s very important that I use the system I’m in charge of trying to optimize.

Q: What advice would you give to a physician who is about to become leader of a program?

A: You need to anticipate growth. I was caught off guard by how fast our program continued to grow, and how quickly we reached the point where we needed more hospitalists. In retrospect, I should have immediately started looking to recruit. I also was not prepared for the financial aspect. If you don’t have a financial background, I would very quickly get training in that area.

Q: What is your biggest challenge as medical director?

A: Getting others in the hospital to accept change, even when all indications are it’s for the better.

Q: Have you identified a strategy that helps make that process easier?

A: The first step is to establish a sense of urgency. Then I try to get people who will be involved in the process or people who don’t oppose change to help set up a vision for the project and communicate that vision. Once you get empowerment to do the project, go for a short, early win that shows the concept is viable and can make it.

Q: How did you develop your interest in information systems?

A: I’ve always been interested in computers and how we can use computerization and informatic systems to improve patient care. When I became a hospitalist, I got much more involved. Decatur Memorial implemented computer physician order entry (CPOE). I became the physician champion for that, and my interest grew from there. I’m fortunate our administration is very good at pushing to improve our information systems.

Q: Does that interest fit with your approach toward medicine?

A: Absolutely. I’m a big believer in evidenced-based medicine. I think computer systems complement that very well.

Q: You were a finalist for McKesson’s Distinguished Achieve-ment Award and received an award this year from the Association of Medical Directors of Information Systems. What were those honors for?

A: We did a complete cultural change with nurses and physicians in terms of how they deal with diabetes. As part of that project, I developed a CPOE order set that automatically calculated the basal, nutritional, and correctional insulin dosage for the physician based on the patient’s weight and height. It made the right thing to do the easy thing to do. The concept involved the use of evidence-based medicine, project improvement with the Six Sigma process, and the high-level use of informatics.

Q: Has that improved patient care?

A: I was able to demonstrate a statistically significant improvement in glucose control without a change in hypoglycemia, so I did demonstrate an improved clinical outcome.

Q: What’s next for you professionally?

A: I have no intention of changing jobs, but I will continue to be very involved in quality projects. The biggest long-term project is developing more patient- and family-centered care at our hospital. I went to a national conference in February, and a big component was patient-centered care. I was very intrigued by it and brought the vision back to our hospital.

Q: Where does the effort stand?

A: I thought our hospitalist group would be a good group to do an initial component of the project. It went over really well, and people started asking me to present it to others. It took on a life of its own, and I wound up on a bit of a lecture series. It has since become an official Six Sigma project. We got the charter for it and it’s going in the hospital’s strategic plan, which I’m very pleased about.

Q: You earned FHM designation earlier this year. What does that mean to you?

A: It means a great deal. It’s tremendous recognition for the work I’ve done, the quality improvement projects I’ve been involved with, and the leadership roles I’ve taken on. At the same time, when you are able to show a national society views your work as important, I think it gives me even more credibility with the administration and the support staff.

Mark Leiser is a freelance writer based in New Jersey.

Like many physicians, Larry Holder, MD, FACP, FHM, entered the medical profession with the desire to make a difference. After completing a fellowship in hematology and oncology in 1988, he joined Cancer Care Specialists of Central Illinois, a community oncology practice based in Decatur, and anticipated a lengthy career in which he would contribute to significant breakthroughs in cancer treatment.

After 12 years, however, he changed direction.

“I had become a bit disillusioned and realized we weren’t making big impacts, especially on the more common cancers,” he says. “I also got very attached to my patients, and in oncology, that’s not always a good thing. It became very trying emotionally.”

Dr. Holder spent the next five years practicing internal medicine at Community Health Improvement Center in Decatur. In 2005, he joined the hospitalist program at Decatur Memorial Hospital. Last year, he became medical director of hospitalist services, chief medical informatics officer (CMIO), and medical director of information systems.

Although he has found a new niche, his philosophy remains the same.

“Everything I do comes down to the fact I still love taking care of patients,” says Dr. Holder, one of six new members of Team Hospitalist. “That’s why I became a doctor. It’s very rewarding, and I never want to give that up.”

As a physician, I still find [clinical work] extremely rewarding. As medical director, I need to be in the trenches to know what the hospitalists are going through and what problems they are having. As CMIO, it’s very important that I use the system I’m in charge of trying to optimize.

Question: You left oncology partly because you became attached to your patients. Does that approach help you as a hospitalist?

Answer: Definitely. I try to teach younger hospitalists the value of developing a rapport with patients. I enjoy building that emotional or intellectual attachment. I’m a big believer in the human aspect of what we do, and it’s one of the aspects of my job I love the most.

Q: Did you join Decatur Memorial with aspirations of leading its hospitalist program?

A: No. My plan was to focus on giving good patient care, get involved on the quality side, and become the CMIO for the hospital. When the medical director role opened up, it seemed to be sitting there waiting to be filled. I structured it so I could continue to see patients and split my administrative time between being the medical director of the hospitalists and being the CMIO.

Q: Why is it so important for you to still see patients?

A: As a physician, I still find it extremely rewarding. As medical director, I need to be in the trenches to know what the hospitalists are going through and what problems they are having. As CMIO, it’s very important that I use the system I’m in charge of trying to optimize.

Q: What advice would you give to a physician who is about to become leader of a program?

A: You need to anticipate growth. I was caught off guard by how fast our program continued to grow, and how quickly we reached the point where we needed more hospitalists. In retrospect, I should have immediately started looking to recruit. I also was not prepared for the financial aspect. If you don’t have a financial background, I would very quickly get training in that area.

Q: What is your biggest challenge as medical director?

A: Getting others in the hospital to accept change, even when all indications are it’s for the better.

Q: Have you identified a strategy that helps make that process easier?

A: The first step is to establish a sense of urgency. Then I try to get people who will be involved in the process or people who don’t oppose change to help set up a vision for the project and communicate that vision. Once you get empowerment to do the project, go for a short, early win that shows the concept is viable and can make it.

Q: How did you develop your interest in information systems?

A: I’ve always been interested in computers and how we can use computerization and informatic systems to improve patient care. When I became a hospitalist, I got much more involved. Decatur Memorial implemented computer physician order entry (CPOE). I became the physician champion for that, and my interest grew from there. I’m fortunate our administration is very good at pushing to improve our information systems.

Q: Does that interest fit with your approach toward medicine?

A: Absolutely. I’m a big believer in evidenced-based medicine. I think computer systems complement that very well.

Q: You were a finalist for McKesson’s Distinguished Achieve-ment Award and received an award this year from the Association of Medical Directors of Information Systems. What were those honors for?

A: We did a complete cultural change with nurses and physicians in terms of how they deal with diabetes. As part of that project, I developed a CPOE order set that automatically calculated the basal, nutritional, and correctional insulin dosage for the physician based on the patient’s weight and height. It made the right thing to do the easy thing to do. The concept involved the use of evidence-based medicine, project improvement with the Six Sigma process, and the high-level use of informatics.

Q: Has that improved patient care?

A: I was able to demonstrate a statistically significant improvement in glucose control without a change in hypoglycemia, so I did demonstrate an improved clinical outcome.

Q: What’s next for you professionally?

A: I have no intention of changing jobs, but I will continue to be very involved in quality projects. The biggest long-term project is developing more patient- and family-centered care at our hospital. I went to a national conference in February, and a big component was patient-centered care. I was very intrigued by it and brought the vision back to our hospital.

Q: Where does the effort stand?

A: I thought our hospitalist group would be a good group to do an initial component of the project. It went over really well, and people started asking me to present it to others. It took on a life of its own, and I wound up on a bit of a lecture series. It has since become an official Six Sigma project. We got the charter for it and it’s going in the hospital’s strategic plan, which I’m very pleased about.

Q: You earned FHM designation earlier this year. What does that mean to you?

A: It means a great deal. It’s tremendous recognition for the work I’ve done, the quality improvement projects I’ve been involved with, and the leadership roles I’ve taken on. At the same time, when you are able to show a national society views your work as important, I think it gives me even more credibility with the administration and the support staff.

Mark Leiser is a freelance writer based in New Jersey.

Like many physicians, Larry Holder, MD, FACP, FHM, entered the medical profession with the desire to make a difference. After completing a fellowship in hematology and oncology in 1988, he joined Cancer Care Specialists of Central Illinois, a community oncology practice based in Decatur, and anticipated a lengthy career in which he would contribute to significant breakthroughs in cancer treatment.

After 12 years, however, he changed direction.

“I had become a bit disillusioned and realized we weren’t making big impacts, especially on the more common cancers,” he says. “I also got very attached to my patients, and in oncology, that’s not always a good thing. It became very trying emotionally.”

Dr. Holder spent the next five years practicing internal medicine at Community Health Improvement Center in Decatur. In 2005, he joined the hospitalist program at Decatur Memorial Hospital. Last year, he became medical director of hospitalist services, chief medical informatics officer (CMIO), and medical director of information systems.

Although he has found a new niche, his philosophy remains the same.

“Everything I do comes down to the fact I still love taking care of patients,” says Dr. Holder, one of six new members of Team Hospitalist. “That’s why I became a doctor. It’s very rewarding, and I never want to give that up.”

As a physician, I still find [clinical work] extremely rewarding. As medical director, I need to be in the trenches to know what the hospitalists are going through and what problems they are having. As CMIO, it’s very important that I use the system I’m in charge of trying to optimize.

Question: You left oncology partly because you became attached to your patients. Does that approach help you as a hospitalist?

Answer: Definitely. I try to teach younger hospitalists the value of developing a rapport with patients. I enjoy building that emotional or intellectual attachment. I’m a big believer in the human aspect of what we do, and it’s one of the aspects of my job I love the most.

Q: Did you join Decatur Memorial with aspirations of leading its hospitalist program?

A: No. My plan was to focus on giving good patient care, get involved on the quality side, and become the CMIO for the hospital. When the medical director role opened up, it seemed to be sitting there waiting to be filled. I structured it so I could continue to see patients and split my administrative time between being the medical director of the hospitalists and being the CMIO.

Q: Why is it so important for you to still see patients?

A: As a physician, I still find it extremely rewarding. As medical director, I need to be in the trenches to know what the hospitalists are going through and what problems they are having. As CMIO, it’s very important that I use the system I’m in charge of trying to optimize.

Q: What advice would you give to a physician who is about to become leader of a program?

A: You need to anticipate growth. I was caught off guard by how fast our program continued to grow, and how quickly we reached the point where we needed more hospitalists. In retrospect, I should have immediately started looking to recruit. I also was not prepared for the financial aspect. If you don’t have a financial background, I would very quickly get training in that area.

Q: What is your biggest challenge as medical director?

A: Getting others in the hospital to accept change, even when all indications are it’s for the better.

Q: Have you identified a strategy that helps make that process easier?

A: The first step is to establish a sense of urgency. Then I try to get people who will be involved in the process or people who don’t oppose change to help set up a vision for the project and communicate that vision. Once you get empowerment to do the project, go for a short, early win that shows the concept is viable and can make it.

Q: How did you develop your interest in information systems?

A: I’ve always been interested in computers and how we can use computerization and informatic systems to improve patient care. When I became a hospitalist, I got much more involved. Decatur Memorial implemented computer physician order entry (CPOE). I became the physician champion for that, and my interest grew from there. I’m fortunate our administration is very good at pushing to improve our information systems.

Q: Does that interest fit with your approach toward medicine?

A: Absolutely. I’m a big believer in evidenced-based medicine. I think computer systems complement that very well.

Q: You were a finalist for McKesson’s Distinguished Achieve-ment Award and received an award this year from the Association of Medical Directors of Information Systems. What were those honors for?

A: We did a complete cultural change with nurses and physicians in terms of how they deal with diabetes. As part of that project, I developed a CPOE order set that automatically calculated the basal, nutritional, and correctional insulin dosage for the physician based on the patient’s weight and height. It made the right thing to do the easy thing to do. The concept involved the use of evidence-based medicine, project improvement with the Six Sigma process, and the high-level use of informatics.

Q: Has that improved patient care?

A: I was able to demonstrate a statistically significant improvement in glucose control without a change in hypoglycemia, so I did demonstrate an improved clinical outcome.

Q: What’s next for you professionally?

A: I have no intention of changing jobs, but I will continue to be very involved in quality projects. The biggest long-term project is developing more patient- and family-centered care at our hospital. I went to a national conference in February, and a big component was patient-centered care. I was very intrigued by it and brought the vision back to our hospital.

Q: Where does the effort stand?

A: I thought our hospitalist group would be a good group to do an initial component of the project. It went over really well, and people started asking me to present it to others. It took on a life of its own, and I wound up on a bit of a lecture series. It has since become an official Six Sigma project. We got the charter for it and it’s going in the hospital’s strategic plan, which I’m very pleased about.

Q: You earned FHM designation earlier this year. What does that mean to you?

A: It means a great deal. It’s tremendous recognition for the work I’ve done, the quality improvement projects I’ve been involved with, and the leadership roles I’ve taken on. At the same time, when you are able to show a national society views your work as important, I think it gives me even more credibility with the administration and the support staff.

Mark Leiser is a freelance writer based in New Jersey.

Pipeline Drugs

• Phentermine/topiramate (Qnexa) is an investigational drug for the treatment of obesity. This includes weight loss and weight-loss maintenance in patients who are obese or overweight with such comorbidities as hypertension, Type 2 diabetes, dyslipidemia, or central adiposity. A new drug application (NDA) was filed with the FDA for this agent late in 2009.1 Qnexa is a once-daily, oral, controlled-release formulation comprised of low-dose phentermine and topiramate, which works on both patient satiety and appetite. Clinical trials show the drug has led to significant weight loss, glycemic control, and improved cardiovascular risk factors. Common side effects in clinical trials were dry mouth, tingling, and constipation.
• Pirfenidone, a potential treatment for idiopathic pulmonary fibrosis (IPF), has been granted a priority review by the FDA.2 Idiopathic pulmonary fibrosis is a disabling and fatal disease characterized by lung inflammation and scarring. The median survival time from diagnosis is two to five years, with an approximate five-year survival rate of 20%. Patients usually are diagnosed between the ages of 20 and 70, with a median of 63 years. It affects slightly more men than women. There are no medications approved to treat this fatal disease. Pirfenidone has been shown to have both antifibrotic and anti-inflammatory properties. The most common side effects are photosensitivity rash and gastrointestinal symptoms.3 The FDA’s action date is expected to be May 4.
• FDA approval was requested for retigabine, a potential new adjunctive epilepsy treatment, on Dec. 30, 2009.4 Retigabine is a neuronal potassium channel opener for use in adults with partial-onset seizures. In Phase 3 clinical trials, common adverse effects (occurring in more than 5% of patients) were dizziness, fatigue, confused state, vertigo, tremor, abnormal coordination, diplopia, attention disturbance, asthenia, and visual blurring.

Safety Information

• Desipramine (Norpramin), a tricyclic antidepressant approved by the FDA for treating major depression in adults, has undergone a label change to reflect new safety information. The “Warnings” and “Overdosage” sections of the product label now include information stating that extreme caution needs to be used when desipramine is administered to patients with a family history of sudden death, cardiac dysrhythmias, and cardiac conduction disturbances. The information also states that seizures might precede cardiac dysrhythmias and death in some patients.5 In a related “Dear Healthcare Professional” letter, information related to this warning was included with regard to identifying patients who present with a desipramine overdose, managing gastrointestinal decontamination with activated charcoal, managing cardiovascular effects, and deletion of measuring plasma-concentration desipramine as a guide to patient monitoring.5
• Diclofenac gel (Voltaren gel), a topical NSAID indicated for the relief of osteoarthritis pain of joints amenable to topical treatment (e.g., knees and hands), has undergone a label change related to its hepatic effects section. The label has revised warnings and precautions about the potential for liver function test elevations while receiving treatment with all diclofenac-containing products.6 There have been post-marketing reports of drug-induced hepatotoxicity within the first month of treatment with this topical agent. However, this reaction can occur at any time during diclofenac treatment. Severe hepatic reactions have been reported, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these cases resulted in fatalities or liver transplantation. Oral diclofenac also is hepatotoxic; it’s one of the most hepatotoxic NSAIDs available. To monitor patients receiving topical diclofenac, you should, after obtaining baseline transaminases, periodically measure transaminases in patients receiving long-term therapy. The optimum times for measurement are unknown. Based on available data from clinical trials and other cases, transaminases should be monitored within four to eight weeks after initiating diclofenac treatment.
• Fosamprenavir (Lexiva) has undergone a label change in the “Warnings” and “Precautions” sections, which is related to a potential association between the agent and the occurrence of myocardial infarction and dyslipidemia in adults with HIV.7 The updated label notes that patient cholesterol levels might increase if treated with fosamprenavir, and that lipid monitoring prior to and after initiating the agent should occur.
• Valproate sodium, valproic acid, and divalproex sodium have been associated with an increased risk of neural tube defects and other major birth defects (e.g., craniofacial defects and cardiovascular malformations) in babies exposed to these agents during pregnancy.8 Healthcare providers need to inform women of childbearing potential about these risks and consider alternative therapies, especially if the use of valproate is considered to treat migraines or other conditions that are not considered life-threatening. Women who are not actively planning a pregnancy and require use of valproate for medical conditions should use contraception, as birth-defect risks are high during the first trimester of pregnancy. Pregnant women using valproate should be encouraged to enroll in the North American Antiepileptic Drug Pregnancy Registry (888-233-2334 or www.aedpregnancyregistry.org). A medication guide explaining the risk and benefits of such treatment is required to be distributed with each dispensed valproate prescription.9 TH

Michele B. Kaufman, PharmD, BSc, RPh, is a freelance medical writer based in New York City and a clinical pharmacist at New York Downtown Hospital.

References

1. NDA submitted for Qnexa. Drugs.com Web site. Available at: http://www.drugs.com/nda/qnexa_091229.html. Accessed Jan. 7, 2010.
2. Todoruk M. InterMune’s pulmonary drug pirfenidone granted priority review by FDA. FirstWord Web site. Available at: http://www.firstwordplus.com/Fws.do?articleid=5C01296C0574469B9A67F3574353FB1E&logRowId=343385. Accessed Jan. 7, 2010.
3. FDA grants priority review of pirfenidone NDA for the treatment of patients with IPF. InterMune Web site. Available at: http://phx.corporate-ir.net/phoenix.zhtml?c=100067&p=irol-newsArticle&ID=1370133&highlight=. Accessed Jan. 7, 2010.
4. FDA accepts NDA filing for retigabine. Drugs.com Web site. Available at: http://www.drugs.com/nda/retigabine_091230.html. Accessed Jan. 7, 2010.
5. Norpramin (desipramine hydrochloride)—Dear Healthcare Professional letter. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192655.htm. Accessed Jan. 7, 2010.
6. Voltaren gel (diclofenac sodium topical gel) 1%—hepatic effects labeling changes. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm193047.htm. Accessed Jan. 7, 2009.
7. Lexiva (fosamprenavir calcium)—Dear Healthcare Professional letter. Food and Drug Administration Web site. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192699.htm. Accessed Jan. 7, 2010.
8. FDA warns of birth defects with valproate sodium, valproic acid, and divalproex sodium. Monthly Prescribing Reference Web site. Available at: http://www.empr.com/fda-warns-of-birth-defects-with-valproate-sodium-valproic-acid-and-divalproex-sodium/article/159034/. Accessed Jan. 7, 2010.
9. Valproate sodium and related products (valproic acid and divalproex sodium): risk of birth defects. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192788.htm. Accessed Jan. 7, 2009.

Pipeline Drugs

• Phentermine/topiramate (Qnexa) is an investigational drug for the treatment of obesity. This includes weight loss and weight-loss maintenance in patients who are obese or overweight with such comorbidities as hypertension, Type 2 diabetes, dyslipidemia, or central adiposity. A new drug application (NDA) was filed with the FDA for this agent late in 2009.1 Qnexa is a once-daily, oral, controlled-release formulation comprised of low-dose phentermine and topiramate, which works on both patient satiety and appetite. Clinical trials show the drug has led to significant weight loss, glycemic control, and improved cardiovascular risk factors. Common side effects in clinical trials were dry mouth, tingling, and constipation.
• Pirfenidone, a potential treatment for idiopathic pulmonary fibrosis (IPF), has been granted a priority review by the FDA.2 Idiopathic pulmonary fibrosis is a disabling and fatal disease characterized by lung inflammation and scarring. The median survival time from diagnosis is two to five years, with an approximate five-year survival rate of 20%. Patients usually are diagnosed between the ages of 20 and 70, with a median of 63 years. It affects slightly more men than women. There are no medications approved to treat this fatal disease. Pirfenidone has been shown to have both antifibrotic and anti-inflammatory properties. The most common side effects are photosensitivity rash and gastrointestinal symptoms.3 The FDA’s action date is expected to be May 4.
• FDA approval was requested for retigabine, a potential new adjunctive epilepsy treatment, on Dec. 30, 2009.4 Retigabine is a neuronal potassium channel opener for use in adults with partial-onset seizures. In Phase 3 clinical trials, common adverse effects (occurring in more than 5% of patients) were dizziness, fatigue, confused state, vertigo, tremor, abnormal coordination, diplopia, attention disturbance, asthenia, and visual blurring.

Safety Information

• Desipramine (Norpramin), a tricyclic antidepressant approved by the FDA for treating major depression in adults, has undergone a label change to reflect new safety information. The “Warnings” and “Overdosage” sections of the product label now include information stating that extreme caution needs to be used when desipramine is administered to patients with a family history of sudden death, cardiac dysrhythmias, and cardiac conduction disturbances. The information also states that seizures might precede cardiac dysrhythmias and death in some patients.5 In a related “Dear Healthcare Professional” letter, information related to this warning was included with regard to identifying patients who present with a desipramine overdose, managing gastrointestinal decontamination with activated charcoal, managing cardiovascular effects, and deletion of measuring plasma-concentration desipramine as a guide to patient monitoring.5
• Diclofenac gel (Voltaren gel), a topical NSAID indicated for the relief of osteoarthritis pain of joints amenable to topical treatment (e.g., knees and hands), has undergone a label change related to its hepatic effects section. The label has revised warnings and precautions about the potential for liver function test elevations while receiving treatment with all diclofenac-containing products.6 There have been post-marketing reports of drug-induced hepatotoxicity within the first month of treatment with this topical agent. However, this reaction can occur at any time during diclofenac treatment. Severe hepatic reactions have been reported, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these cases resulted in fatalities or liver transplantation. Oral diclofenac also is hepatotoxic; it’s one of the most hepatotoxic NSAIDs available. To monitor patients receiving topical diclofenac, you should, after obtaining baseline transaminases, periodically measure transaminases in patients receiving long-term therapy. The optimum times for measurement are unknown. Based on available data from clinical trials and other cases, transaminases should be monitored within four to eight weeks after initiating diclofenac treatment.
• Fosamprenavir (Lexiva) has undergone a label change in the “Warnings” and “Precautions” sections, which is related to a potential association between the agent and the occurrence of myocardial infarction and dyslipidemia in adults with HIV.7 The updated label notes that patient cholesterol levels might increase if treated with fosamprenavir, and that lipid monitoring prior to and after initiating the agent should occur.
• Valproate sodium, valproic acid, and divalproex sodium have been associated with an increased risk of neural tube defects and other major birth defects (e.g., craniofacial defects and cardiovascular malformations) in babies exposed to these agents during pregnancy.8 Healthcare providers need to inform women of childbearing potential about these risks and consider alternative therapies, especially if the use of valproate is considered to treat migraines or other conditions that are not considered life-threatening. Women who are not actively planning a pregnancy and require use of valproate for medical conditions should use contraception, as birth-defect risks are high during the first trimester of pregnancy. Pregnant women using valproate should be encouraged to enroll in the North American Antiepileptic Drug Pregnancy Registry (888-233-2334 or www.aedpregnancyregistry.org). A medication guide explaining the risk and benefits of such treatment is required to be distributed with each dispensed valproate prescription.9 TH

Michele B. Kaufman, PharmD, BSc, RPh, is a freelance medical writer based in New York City and a clinical pharmacist at New York Downtown Hospital.

References

1. NDA submitted for Qnexa. Drugs.com Web site. Available at: http://www.drugs.com/nda/qnexa_091229.html. Accessed Jan. 7, 2010.
2. Todoruk M. InterMune’s pulmonary drug pirfenidone granted priority review by FDA. FirstWord Web site. Available at: http://www.firstwordplus.com/Fws.do?articleid=5C01296C0574469B9A67F3574353FB1E&logRowId=343385. Accessed Jan. 7, 2010.
3. FDA grants priority review of pirfenidone NDA for the treatment of patients with IPF. InterMune Web site. Available at: http://phx.corporate-ir.net/phoenix.zhtml?c=100067&p=irol-newsArticle&ID=1370133&highlight=. Accessed Jan. 7, 2010.
4. FDA accepts NDA filing for retigabine. Drugs.com Web site. Available at: http://www.drugs.com/nda/retigabine_091230.html. Accessed Jan. 7, 2010.
5. Norpramin (desipramine hydrochloride)—Dear Healthcare Professional letter. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192655.htm. Accessed Jan. 7, 2010.
6. Voltaren gel (diclofenac sodium topical gel) 1%—hepatic effects labeling changes. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm193047.htm. Accessed Jan. 7, 2009.
7. Lexiva (fosamprenavir calcium)—Dear Healthcare Professional letter. Food and Drug Administration Web site. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192699.htm. Accessed Jan. 7, 2010.
8. FDA warns of birth defects with valproate sodium, valproic acid, and divalproex sodium. Monthly Prescribing Reference Web site. Available at: http://www.empr.com/fda-warns-of-birth-defects-with-valproate-sodium-valproic-acid-and-divalproex-sodium/article/159034/. Accessed Jan. 7, 2010.
9. Valproate sodium and related products (valproic acid and divalproex sodium): risk of birth defects. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192788.htm. Accessed Jan. 7, 2009.

Pipeline Drugs

• Phentermine/topiramate (Qnexa) is an investigational drug for the treatment of obesity. This includes weight loss and weight-loss maintenance in patients who are obese or overweight with such comorbidities as hypertension, Type 2 diabetes, dyslipidemia, or central adiposity. A new drug application (NDA) was filed with the FDA for this agent late in 2009.1 Qnexa is a once-daily, oral, controlled-release formulation comprised of low-dose phentermine and topiramate, which works on both patient satiety and appetite. Clinical trials show the drug has led to significant weight loss, glycemic control, and improved cardiovascular risk factors. Common side effects in clinical trials were dry mouth, tingling, and constipation.
• Pirfenidone, a potential treatment for idiopathic pulmonary fibrosis (IPF), has been granted a priority review by the FDA.2 Idiopathic pulmonary fibrosis is a disabling and fatal disease characterized by lung inflammation and scarring. The median survival time from diagnosis is two to five years, with an approximate five-year survival rate of 20%. Patients usually are diagnosed between the ages of 20 and 70, with a median of 63 years. It affects slightly more men than women. There are no medications approved to treat this fatal disease. Pirfenidone has been shown to have both antifibrotic and anti-inflammatory properties. The most common side effects are photosensitivity rash and gastrointestinal symptoms.3 The FDA’s action date is expected to be May 4.
• FDA approval was requested for retigabine, a potential new adjunctive epilepsy treatment, on Dec. 30, 2009.4 Retigabine is a neuronal potassium channel opener for use in adults with partial-onset seizures. In Phase 3 clinical trials, common adverse effects (occurring in more than 5% of patients) were dizziness, fatigue, confused state, vertigo, tremor, abnormal coordination, diplopia, attention disturbance, asthenia, and visual blurring.

Safety Information

• Desipramine (Norpramin), a tricyclic antidepressant approved by the FDA for treating major depression in adults, has undergone a label change to reflect new safety information. The “Warnings” and “Overdosage” sections of the product label now include information stating that extreme caution needs to be used when desipramine is administered to patients with a family history of sudden death, cardiac dysrhythmias, and cardiac conduction disturbances. The information also states that seizures might precede cardiac dysrhythmias and death in some patients.5 In a related “Dear Healthcare Professional” letter, information related to this warning was included with regard to identifying patients who present with a desipramine overdose, managing gastrointestinal decontamination with activated charcoal, managing cardiovascular effects, and deletion of measuring plasma-concentration desipramine as a guide to patient monitoring.5
• Diclofenac gel (Voltaren gel), a topical NSAID indicated for the relief of osteoarthritis pain of joints amenable to topical treatment (e.g., knees and hands), has undergone a label change related to its hepatic effects section. The label has revised warnings and precautions about the potential for liver function test elevations while receiving treatment with all diclofenac-containing products.6 There have been post-marketing reports of drug-induced hepatotoxicity within the first month of treatment with this topical agent. However, this reaction can occur at any time during diclofenac treatment. Severe hepatic reactions have been reported, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these cases resulted in fatalities or liver transplantation. Oral diclofenac also is hepatotoxic; it’s one of the most hepatotoxic NSAIDs available. To monitor patients receiving topical diclofenac, you should, after obtaining baseline transaminases, periodically measure transaminases in patients receiving long-term therapy. The optimum times for measurement are unknown. Based on available data from clinical trials and other cases, transaminases should be monitored within four to eight weeks after initiating diclofenac treatment.
• Fosamprenavir (Lexiva) has undergone a label change in the “Warnings” and “Precautions” sections, which is related to a potential association between the agent and the occurrence of myocardial infarction and dyslipidemia in adults with HIV.7 The updated label notes that patient cholesterol levels might increase if treated with fosamprenavir, and that lipid monitoring prior to and after initiating the agent should occur.
• Valproate sodium, valproic acid, and divalproex sodium have been associated with an increased risk of neural tube defects and other major birth defects (e.g., craniofacial defects and cardiovascular malformations) in babies exposed to these agents during pregnancy.8 Healthcare providers need to inform women of childbearing potential about these risks and consider alternative therapies, especially if the use of valproate is considered to treat migraines or other conditions that are not considered life-threatening. Women who are not actively planning a pregnancy and require use of valproate for medical conditions should use contraception, as birth-defect risks are high during the first trimester of pregnancy. Pregnant women using valproate should be encouraged to enroll in the North American Antiepileptic Drug Pregnancy Registry (888-233-2334 or www.aedpregnancyregistry.org). A medication guide explaining the risk and benefits of such treatment is required to be distributed with each dispensed valproate prescription.9 TH

Michele B. Kaufman, PharmD, BSc, RPh, is a freelance medical writer based in New York City and a clinical pharmacist at New York Downtown Hospital.

References

1. NDA submitted for Qnexa. Drugs.com Web site. Available at: http://www.drugs.com/nda/qnexa_091229.html. Accessed Jan. 7, 2010.
2. Todoruk M. InterMune’s pulmonary drug pirfenidone granted priority review by FDA. FirstWord Web site. Available at: http://www.firstwordplus.com/Fws.do?articleid=5C01296C0574469B9A67F3574353FB1E&logRowId=343385. Accessed Jan. 7, 2010.
3. FDA grants priority review of pirfenidone NDA for the treatment of patients with IPF. InterMune Web site. Available at: http://phx.corporate-ir.net/phoenix.zhtml?c=100067&p=irol-newsArticle&ID=1370133&highlight=. Accessed Jan. 7, 2010.
4. FDA accepts NDA filing for retigabine. Drugs.com Web site. Available at: http://www.drugs.com/nda/retigabine_091230.html. Accessed Jan. 7, 2010.
5. Norpramin (desipramine hydrochloride)—Dear Healthcare Professional letter. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192655.htm. Accessed Jan. 7, 2010.
6. Voltaren gel (diclofenac sodium topical gel) 1%—hepatic effects labeling changes. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm193047.htm. Accessed Jan. 7, 2009.
7. Lexiva (fosamprenavir calcium)—Dear Healthcare Professional letter. Food and Drug Administration Web site. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192699.htm. Accessed Jan. 7, 2010.
8. FDA warns of birth defects with valproate sodium, valproic acid, and divalproex sodium. Monthly Prescribing Reference Web site. Available at: http://www.empr.com/fda-warns-of-birth-defects-with-valproate-sodium-valproic-acid-and-divalproex-sodium/article/159034/. Accessed Jan. 7, 2010.
9. Valproate sodium and related products (valproic acid and divalproex sodium): risk of birth defects. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192788.htm. Accessed Jan. 7, 2009.