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Author(s)

Michele B. Kaufman, PharmD, BSc, RPh

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

NDA submitted for Qnexa. Drugs.com Web site. Available at: http://www.drugs.com/nda/qnexa_091229.html. Accessed Jan. 7, 2010.

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.

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.

FDA accepts NDA filing for retigabine. Drugs.com Web site. Available at: http://www.drugs.com/nda/retigabine_091230.html. Accessed Jan. 7, 2010.

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.

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.

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.

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.

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.

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The Hospitalist - 2010(04)

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Quality

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Career

Clinical

All Content

Author(s)

Michele B. Kaufman, PharmD, BSc, RPh

Author(s)

Michele B. Kaufman, PharmD, BSc, RPh

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

NDA submitted for Qnexa. Drugs.com Web site. Available at: http://www.drugs.com/nda/qnexa_091229.html. Accessed Jan. 7, 2010.

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.

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.

FDA accepts NDA filing for retigabine. Drugs.com Web site. Available at: http://www.drugs.com/nda/retigabine_091230.html. Accessed Jan. 7, 2010.

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.

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.

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.

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.

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

NDA submitted for Qnexa. Drugs.com Web site. Available at: http://www.drugs.com/nda/qnexa_091229.html. Accessed Jan. 7, 2010.

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.

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.

FDA accepts NDA filing for retigabine. Drugs.com Web site. Available at: http://www.drugs.com/nda/retigabine_091230.html. Accessed Jan. 7, 2010.

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.

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.

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.

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.

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.