Michele B. Kaufman, PharmD

New Generics

• Desloratadine tablets (generic Clarinex)¹
• Didanosine delayed-release capsules (Generic Videx EC)²

New Indications, Dosage Forms, and Recommendations

• Ganciclovir ophthalmic gel 0.15% (Zirgan) has been approved by the FDA for treating acute herpetic keratitis.³ The recommended dose is one drop in the affected eye five times daily until the ulcer heals, then one drop three times daily for seven more days. The most common side effects in clinical trials were blurred vision, eye irritation, punctate keratitis, and conjunctival hyperemia. It will be available in a 5-g tube.
• Immune globulin intravenous 10% liquid (human) (Privigen) has received an updated approval from the FDA, which allows for room temperature storage throughout its entire 36-month shelf life.⁴ The agent is used to treat patients with primary immunodeficiency disorders.
• Miconazole buccal tablets (Oravig) have been approved by the FDA for treating oropharyngeal candidiasis in adults and children 16 years of age and older. It is the first, and currently the only local, buccal prescription formulation of miconazole.⁵ The buccal tablet was developed to adhere to the gum. It should not be crushed, chewed, or swallowed. The most common adverse effects in clinical trials were diarrhea, nausea, headache, dysgeusia, upper abdominal pain, and vomiting. It is recommended to monitor patients with a history of hypersensitivity to azoles, as there is no information regarding cross-reactivity between miconazole and other azole agents.
• A supplemental new drug application (sNDA) has been submitted to the FDA for naltrexone extended-release injectable suspension (Vivitrol) for treating opioid dependence.⁶ It is administered as a once-monthly intramuscular injection and currently is approved by the FDA for treating alcohol dependence.
• Oxycodone controlled-release (OxyContin) has been approved by the FDA in a new, abuse-deterrent formulation.⁷
• Pancrelipase delayed-release capsules (Pancreaze) joins Creon (Abbott Labs) and Zenpep (Eurand) as the third pancreatic enzyme product (PEP) to be approved by the FDA for treating exocrine pancreatic insufficiency.⁸
• Pramipexole extended-release tablets (Mirapex ER) have been approved by the FDA as a once-daily treatment for the signs and symptoms of idiopathic Parkinson’s disease (early and late).⁹
• The active ingredient in the vaccine Diamyd, rhGAD65, has received orphan drug status for treating Type 1 diabetes mellitus (T1DM) with residual beta cell function.^10,11 This agent is in Phase 3 clinical trials and is being investigated to determine whether it can stop or slow the autoimmune destruction of insulin-producing beta cell function. The DiaPrevent study is enrolling patients. In Phase 2 studies, the agent preserved remaining beta cell function in adolescents and children recently diagnosed with T1DM.
• Warfarin genetic diagnostic: Machaon Diagnostics has received FDA approval for an array-based diagnostic technology that detects genetic variation and could aid in determining an accurate initial warfarin dose.¹² At least 40% of Americans have at least one genetic variation involved in warfarin metabolism, which can cause a more than fivefold disparity in the weekly warfarin dose. This test can be used to more accurately determine dosing for warfarin-treated patients.

Pipeline

• The NDA for DM-1796 (gabapentin extended-release tablet) has been submitted to the FDA for treatment of postherpetic neuralgia.¹³ It is a once-daily, extended-release formulation of gabapentin.
• The “quad” combination of elvitegravir, cobicistat (formerly GS 9350), emtricitabine, and tenofovir disoproxil fumarate in a fixed-dose single tablet is currently in Phase 3 clinical trials for treatment of HIV.¹⁴
• FTY720 is an investigational oral immune modulator agent for treating relapsing-remitting multiple sclerosis (RR-MS).¹⁵ The NDA for this agent was submitted in December 2009; the FDA granted it a priority review in February. Two-year data from the FREEDOMS trial showed that FTY720 reduced annual relapse rates by 62%, compared with treatment-naive patients. For patients that had received prior treatments, the annual relapse rate was reduced by 44%. At two years, FTY720 delayed disability progression by 30% for patients treated with 0.5 mg, compared with placebo. The serious infection rate was comparable in the different “immune modulator” treatment groups.

Product Removal

Inhalers containing ozone-depleting chlorofluorocarbons (CFCs) are continuing to be phased out.¹⁶ These agents are used to treat asthma and COPD, and alternate products that do not contain CFCs are available. Some pharmacies might be depleting stock after the “last-sale date.” The affected products and their phase-out dates are:

• Tilade (nedocromil): June 14, 2010;
• Alupent (metaproterenol): June 14, 2010;
• Aerobid (flunisolide): June 30, 2010;
• Azmacort (triamcinolone): Dec. 31, 2010;
• Intal (cromolyn): Dec. 31, 2010;
• Combivent (albuterol/ipratropium): December 31, 2013; and
• Maxair (pirbuterol) autohaler: December 31, 2013. 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. Orange Book: Approved drug products with therapeutic equivalence evaluations. U.S. Food and Drug Administration website. Available at: www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=078357&TABLE1=OB_Rx. Accessed April 27, 2010.
2. Mylan announces approval under PEPFAR for generic version of Videx EC HIV treatment. Medical News Today website. Available at: www.medicalnewstoday.com/articles/186273.php. Accessed April 27, 2010.
3. Sirion Therapeutics announces availability of Zirgan (ganciclovir ophthalmic gel) 0.15% for ocular herpes. PR Newswire website. Available at: www.prnewswire.com/news-releases/sirion-therapeutics-announces-availability-of-zirgantm-ganciclovir-ophthalmic-gel-015-for-ocular-herpes-92084614.html. Accessed April 27, 2010.
4. CSL Behring receives FDA approval to extend shelf life for Privigen from 24 to 36 months. CSL Behring website. Available at: www.cslbehring-us.com/s1/cs/enus/1154272074489/news/1255923905944/prdetail.htm. Accessed April 27, 2010.
5. FDA approves Oravig (miconazole) buccal tablets for treatment of oropharyngeal candidiasis. PAR Pharmaceuticals website. Available at: investors.parpharm.com/phoenix.zhtml?c=81806&p=irol-newsArticle&ID=1413993&highlight=. Accessed April 27, 2010.
6. Alkermes submits supplemental new drug application for Vivitrol for the treatment of opioid dependence. Medical News Today website. Available at: www.medicalnewstoday.com/articles/185456.php. Accessed April 27, 2010.
7. FDA approves reformulated oxycontin. Contract Pharma website. www.contractpharma.com/news/2010/04/07/fda_approves_reformulated_oxycontin. Accessed April 27, 2010.
8. Gansz Bobo E. FDA approves pancreatic enzyme product, Pancreaze. FDA website. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm208135.htm. Accessed April 27, 2010.
9. Once-daily Mirapex ER now approved by FDA for both early and advanced Parkinson’s disease. Medical News Today website. Available at: www.medicalnewstoday.com/printerfriendlynews.php?newsid=183272. Accessed April 27, 2010.
10. DiaPrevent diabetes research. DiaPrevent website. Available at: www.diaprevent.diamyd.com/. Accessed April 27, 2010.
11. Diamyd granted orphan drug designation in the US. Diamyd website. Available at: www.diamyd.com/docs/pressClip.aspx?section=investor&ClipID=479460. Accessed April 27, 2010.
12. Same-day genetic testing service available for safer warfarin dosing. Monthly Prescribing Reference website. Available at: www.empr.com/same-day-genetic-testing-service-available-for-safer-warfarin-dosing/article/167586/. Accessed April 27, 2010.
13. NDA submitted for DM-1796 for postherpetic neuralgia (PHN). Monthly Prescribing Reference website. Available at: www.empr.com/nda-submitted-for-dm-1796-for-postherpetic-neuralgia-phn/article/167056/. Accessed April 26, 2010.
14. Gilead initiates Phase III clinical program evaluating single-table, once-daily “quad” regimen for HIV. Gilead website. Available at: www.gilead.com/pr_1411934. Accessed April 27, 2010.
15. Novartis investigational multiple sclerosis therapy Gilenia (FTY720) shown to reduce relapse rates regardless of treatment history. Drugs.com website. Available at: www.drugs.com/clinical_trials/novartis-investigational-multiple-sclerosis-therapy-gilenia-fty720-shown-reduce-relapse-rates-9139.html. Accessed April 27, 2010.
16. Inhalers containing CFCs being eliminated. Pharamacist eLink website. Available at: www.pharmacistelink.com/index.php/Drugs-and-Treatment/Inhalers-containing-CFC-s-being-eliminated.html. Accessed April 27, 2010.

New Generics

• Desloratadine tablets (generic Clarinex)¹
• Didanosine delayed-release capsules (Generic Videx EC)²

New Indications, Dosage Forms, and Recommendations

• Ganciclovir ophthalmic gel 0.15% (Zirgan) has been approved by the FDA for treating acute herpetic keratitis.³ The recommended dose is one drop in the affected eye five times daily until the ulcer heals, then one drop three times daily for seven more days. The most common side effects in clinical trials were blurred vision, eye irritation, punctate keratitis, and conjunctival hyperemia. It will be available in a 5-g tube.
• Immune globulin intravenous 10% liquid (human) (Privigen) has received an updated approval from the FDA, which allows for room temperature storage throughout its entire 36-month shelf life.⁴ The agent is used to treat patients with primary immunodeficiency disorders.
• Miconazole buccal tablets (Oravig) have been approved by the FDA for treating oropharyngeal candidiasis in adults and children 16 years of age and older. It is the first, and currently the only local, buccal prescription formulation of miconazole.⁵ The buccal tablet was developed to adhere to the gum. It should not be crushed, chewed, or swallowed. The most common adverse effects in clinical trials were diarrhea, nausea, headache, dysgeusia, upper abdominal pain, and vomiting. It is recommended to monitor patients with a history of hypersensitivity to azoles, as there is no information regarding cross-reactivity between miconazole and other azole agents.
• A supplemental new drug application (sNDA) has been submitted to the FDA for naltrexone extended-release injectable suspension (Vivitrol) for treating opioid dependence.⁶ It is administered as a once-monthly intramuscular injection and currently is approved by the FDA for treating alcohol dependence.
• Oxycodone controlled-release (OxyContin) has been approved by the FDA in a new, abuse-deterrent formulation.⁷
• Pancrelipase delayed-release capsules (Pancreaze) joins Creon (Abbott Labs) and Zenpep (Eurand) as the third pancreatic enzyme product (PEP) to be approved by the FDA for treating exocrine pancreatic insufficiency.⁸
• Pramipexole extended-release tablets (Mirapex ER) have been approved by the FDA as a once-daily treatment for the signs and symptoms of idiopathic Parkinson’s disease (early and late).⁹
• The active ingredient in the vaccine Diamyd, rhGAD65, has received orphan drug status for treating Type 1 diabetes mellitus (T1DM) with residual beta cell function.^10,11 This agent is in Phase 3 clinical trials and is being investigated to determine whether it can stop or slow the autoimmune destruction of insulin-producing beta cell function. The DiaPrevent study is enrolling patients. In Phase 2 studies, the agent preserved remaining beta cell function in adolescents and children recently diagnosed with T1DM.
• Warfarin genetic diagnostic: Machaon Diagnostics has received FDA approval for an array-based diagnostic technology that detects genetic variation and could aid in determining an accurate initial warfarin dose.¹² At least 40% of Americans have at least one genetic variation involved in warfarin metabolism, which can cause a more than fivefold disparity in the weekly warfarin dose. This test can be used to more accurately determine dosing for warfarin-treated patients.

Pipeline

• The NDA for DM-1796 (gabapentin extended-release tablet) has been submitted to the FDA for treatment of postherpetic neuralgia.¹³ It is a once-daily, extended-release formulation of gabapentin.
• The “quad” combination of elvitegravir, cobicistat (formerly GS 9350), emtricitabine, and tenofovir disoproxil fumarate in a fixed-dose single tablet is currently in Phase 3 clinical trials for treatment of HIV.¹⁴
• FTY720 is an investigational oral immune modulator agent for treating relapsing-remitting multiple sclerosis (RR-MS).¹⁵ The NDA for this agent was submitted in December 2009; the FDA granted it a priority review in February. Two-year data from the FREEDOMS trial showed that FTY720 reduced annual relapse rates by 62%, compared with treatment-naive patients. For patients that had received prior treatments, the annual relapse rate was reduced by 44%. At two years, FTY720 delayed disability progression by 30% for patients treated with 0.5 mg, compared with placebo. The serious infection rate was comparable in the different “immune modulator” treatment groups.

Product Removal

Inhalers containing ozone-depleting chlorofluorocarbons (CFCs) are continuing to be phased out.¹⁶ These agents are used to treat asthma and COPD, and alternate products that do not contain CFCs are available. Some pharmacies might be depleting stock after the “last-sale date.” The affected products and their phase-out dates are:

• Tilade (nedocromil): June 14, 2010;
• Alupent (metaproterenol): June 14, 2010;
• Aerobid (flunisolide): June 30, 2010;
• Azmacort (triamcinolone): Dec. 31, 2010;
• Intal (cromolyn): Dec. 31, 2010;
• Combivent (albuterol/ipratropium): December 31, 2013; and
• Maxair (pirbuterol) autohaler: December 31, 2013. 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. Orange Book: Approved drug products with therapeutic equivalence evaluations. U.S. Food and Drug Administration website. Available at: www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=078357&TABLE1=OB_Rx. Accessed April 27, 2010.
2. Mylan announces approval under PEPFAR for generic version of Videx EC HIV treatment. Medical News Today website. Available at: www.medicalnewstoday.com/articles/186273.php. Accessed April 27, 2010.
3. Sirion Therapeutics announces availability of Zirgan (ganciclovir ophthalmic gel) 0.15% for ocular herpes. PR Newswire website. Available at: www.prnewswire.com/news-releases/sirion-therapeutics-announces-availability-of-zirgantm-ganciclovir-ophthalmic-gel-015-for-ocular-herpes-92084614.html. Accessed April 27, 2010.
4. CSL Behring receives FDA approval to extend shelf life for Privigen from 24 to 36 months. CSL Behring website. Available at: www.cslbehring-us.com/s1/cs/enus/1154272074489/news/1255923905944/prdetail.htm. Accessed April 27, 2010.
5. FDA approves Oravig (miconazole) buccal tablets for treatment of oropharyngeal candidiasis. PAR Pharmaceuticals website. Available at: investors.parpharm.com/phoenix.zhtml?c=81806&p=irol-newsArticle&ID=1413993&highlight=. Accessed April 27, 2010.
6. Alkermes submits supplemental new drug application for Vivitrol for the treatment of opioid dependence. Medical News Today website. Available at: www.medicalnewstoday.com/articles/185456.php. Accessed April 27, 2010.
7. FDA approves reformulated oxycontin. Contract Pharma website. www.contractpharma.com/news/2010/04/07/fda_approves_reformulated_oxycontin. Accessed April 27, 2010.
8. Gansz Bobo E. FDA approves pancreatic enzyme product, Pancreaze. FDA website. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm208135.htm. Accessed April 27, 2010.
9. Once-daily Mirapex ER now approved by FDA for both early and advanced Parkinson’s disease. Medical News Today website. Available at: www.medicalnewstoday.com/printerfriendlynews.php?newsid=183272. Accessed April 27, 2010.
10. DiaPrevent diabetes research. DiaPrevent website. Available at: www.diaprevent.diamyd.com/. Accessed April 27, 2010.
11. Diamyd granted orphan drug designation in the US. Diamyd website. Available at: www.diamyd.com/docs/pressClip.aspx?section=investor&ClipID=479460. Accessed April 27, 2010.
12. Same-day genetic testing service available for safer warfarin dosing. Monthly Prescribing Reference website. Available at: www.empr.com/same-day-genetic-testing-service-available-for-safer-warfarin-dosing/article/167586/. Accessed April 27, 2010.
13. NDA submitted for DM-1796 for postherpetic neuralgia (PHN). Monthly Prescribing Reference website. Available at: www.empr.com/nda-submitted-for-dm-1796-for-postherpetic-neuralgia-phn/article/167056/. Accessed April 26, 2010.
14. Gilead initiates Phase III clinical program evaluating single-table, once-daily “quad” regimen for HIV. Gilead website. Available at: www.gilead.com/pr_1411934. Accessed April 27, 2010.
15. Novartis investigational multiple sclerosis therapy Gilenia (FTY720) shown to reduce relapse rates regardless of treatment history. Drugs.com website. Available at: www.drugs.com/clinical_trials/novartis-investigational-multiple-sclerosis-therapy-gilenia-fty720-shown-reduce-relapse-rates-9139.html. Accessed April 27, 2010.
16. Inhalers containing CFCs being eliminated. Pharamacist eLink website. Available at: www.pharmacistelink.com/index.php/Drugs-and-Treatment/Inhalers-containing-CFC-s-being-eliminated.html. Accessed April 27, 2010.

New Generics

• Desloratadine tablets (generic Clarinex)¹
• Didanosine delayed-release capsules (Generic Videx EC)²

New Indications, Dosage Forms, and Recommendations

• Ganciclovir ophthalmic gel 0.15% (Zirgan) has been approved by the FDA for treating acute herpetic keratitis.³ The recommended dose is one drop in the affected eye five times daily until the ulcer heals, then one drop three times daily for seven more days. The most common side effects in clinical trials were blurred vision, eye irritation, punctate keratitis, and conjunctival hyperemia. It will be available in a 5-g tube.
• Immune globulin intravenous 10% liquid (human) (Privigen) has received an updated approval from the FDA, which allows for room temperature storage throughout its entire 36-month shelf life.⁴ The agent is used to treat patients with primary immunodeficiency disorders.
• Miconazole buccal tablets (Oravig) have been approved by the FDA for treating oropharyngeal candidiasis in adults and children 16 years of age and older. It is the first, and currently the only local, buccal prescription formulation of miconazole.⁵ The buccal tablet was developed to adhere to the gum. It should not be crushed, chewed, or swallowed. The most common adverse effects in clinical trials were diarrhea, nausea, headache, dysgeusia, upper abdominal pain, and vomiting. It is recommended to monitor patients with a history of hypersensitivity to azoles, as there is no information regarding cross-reactivity between miconazole and other azole agents.
• A supplemental new drug application (sNDA) has been submitted to the FDA for naltrexone extended-release injectable suspension (Vivitrol) for treating opioid dependence.⁶ It is administered as a once-monthly intramuscular injection and currently is approved by the FDA for treating alcohol dependence.
• Oxycodone controlled-release (OxyContin) has been approved by the FDA in a new, abuse-deterrent formulation.⁷
• Pancrelipase delayed-release capsules (Pancreaze) joins Creon (Abbott Labs) and Zenpep (Eurand) as the third pancreatic enzyme product (PEP) to be approved by the FDA for treating exocrine pancreatic insufficiency.⁸
• Pramipexole extended-release tablets (Mirapex ER) have been approved by the FDA as a once-daily treatment for the signs and symptoms of idiopathic Parkinson’s disease (early and late).⁹
• The active ingredient in the vaccine Diamyd, rhGAD65, has received orphan drug status for treating Type 1 diabetes mellitus (T1DM) with residual beta cell function.^10,11 This agent is in Phase 3 clinical trials and is being investigated to determine whether it can stop or slow the autoimmune destruction of insulin-producing beta cell function. The DiaPrevent study is enrolling patients. In Phase 2 studies, the agent preserved remaining beta cell function in adolescents and children recently diagnosed with T1DM.
• Warfarin genetic diagnostic: Machaon Diagnostics has received FDA approval for an array-based diagnostic technology that detects genetic variation and could aid in determining an accurate initial warfarin dose.¹² At least 40% of Americans have at least one genetic variation involved in warfarin metabolism, which can cause a more than fivefold disparity in the weekly warfarin dose. This test can be used to more accurately determine dosing for warfarin-treated patients.

Pipeline

• The NDA for DM-1796 (gabapentin extended-release tablet) has been submitted to the FDA for treatment of postherpetic neuralgia.¹³ It is a once-daily, extended-release formulation of gabapentin.
• The “quad” combination of elvitegravir, cobicistat (formerly GS 9350), emtricitabine, and tenofovir disoproxil fumarate in a fixed-dose single tablet is currently in Phase 3 clinical trials for treatment of HIV.¹⁴
• FTY720 is an investigational oral immune modulator agent for treating relapsing-remitting multiple sclerosis (RR-MS).¹⁵ The NDA for this agent was submitted in December 2009; the FDA granted it a priority review in February. Two-year data from the FREEDOMS trial showed that FTY720 reduced annual relapse rates by 62%, compared with treatment-naive patients. For patients that had received prior treatments, the annual relapse rate was reduced by 44%. At two years, FTY720 delayed disability progression by 30% for patients treated with 0.5 mg, compared with placebo. The serious infection rate was comparable in the different “immune modulator” treatment groups.

Product Removal

Inhalers containing ozone-depleting chlorofluorocarbons (CFCs) are continuing to be phased out.¹⁶ These agents are used to treat asthma and COPD, and alternate products that do not contain CFCs are available. Some pharmacies might be depleting stock after the “last-sale date.” The affected products and their phase-out dates are:

• Tilade (nedocromil): June 14, 2010;
• Alupent (metaproterenol): June 14, 2010;
• Aerobid (flunisolide): June 30, 2010;
• Azmacort (triamcinolone): Dec. 31, 2010;
• Intal (cromolyn): Dec. 31, 2010;
• Combivent (albuterol/ipratropium): December 31, 2013; and
• Maxair (pirbuterol) autohaler: December 31, 2013. 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. Orange Book: Approved drug products with therapeutic equivalence evaluations. U.S. Food and Drug Administration website. Available at: www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=078357&TABLE1=OB_Rx. Accessed April 27, 2010.
2. Mylan announces approval under PEPFAR for generic version of Videx EC HIV treatment. Medical News Today website. Available at: www.medicalnewstoday.com/articles/186273.php. Accessed April 27, 2010.
3. Sirion Therapeutics announces availability of Zirgan (ganciclovir ophthalmic gel) 0.15% for ocular herpes. PR Newswire website. Available at: www.prnewswire.com/news-releases/sirion-therapeutics-announces-availability-of-zirgantm-ganciclovir-ophthalmic-gel-015-for-ocular-herpes-92084614.html. Accessed April 27, 2010.
4. CSL Behring receives FDA approval to extend shelf life for Privigen from 24 to 36 months. CSL Behring website. Available at: www.cslbehring-us.com/s1/cs/enus/1154272074489/news/1255923905944/prdetail.htm. Accessed April 27, 2010.
5. FDA approves Oravig (miconazole) buccal tablets for treatment of oropharyngeal candidiasis. PAR Pharmaceuticals website. Available at: investors.parpharm.com/phoenix.zhtml?c=81806&p=irol-newsArticle&ID=1413993&highlight=. Accessed April 27, 2010.
6. Alkermes submits supplemental new drug application for Vivitrol for the treatment of opioid dependence. Medical News Today website. Available at: www.medicalnewstoday.com/articles/185456.php. Accessed April 27, 2010.
7. FDA approves reformulated oxycontin. Contract Pharma website. www.contractpharma.com/news/2010/04/07/fda_approves_reformulated_oxycontin. Accessed April 27, 2010.
8. Gansz Bobo E. FDA approves pancreatic enzyme product, Pancreaze. FDA website. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm208135.htm. Accessed April 27, 2010.
9. Once-daily Mirapex ER now approved by FDA for both early and advanced Parkinson’s disease. Medical News Today website. Available at: www.medicalnewstoday.com/printerfriendlynews.php?newsid=183272. Accessed April 27, 2010.
10. DiaPrevent diabetes research. DiaPrevent website. Available at: www.diaprevent.diamyd.com/. Accessed April 27, 2010.
11. Diamyd granted orphan drug designation in the US. Diamyd website. Available at: www.diamyd.com/docs/pressClip.aspx?section=investor&ClipID=479460. Accessed April 27, 2010.
12. Same-day genetic testing service available for safer warfarin dosing. Monthly Prescribing Reference website. Available at: www.empr.com/same-day-genetic-testing-service-available-for-safer-warfarin-dosing/article/167586/. Accessed April 27, 2010.
13. NDA submitted for DM-1796 for postherpetic neuralgia (PHN). Monthly Prescribing Reference website. Available at: www.empr.com/nda-submitted-for-dm-1796-for-postherpetic-neuralgia-phn/article/167056/. Accessed April 26, 2010.
14. Gilead initiates Phase III clinical program evaluating single-table, once-daily “quad” regimen for HIV. Gilead website. Available at: www.gilead.com/pr_1411934. Accessed April 27, 2010.
15. Novartis investigational multiple sclerosis therapy Gilenia (FTY720) shown to reduce relapse rates regardless of treatment history. Drugs.com website. Available at: www.drugs.com/clinical_trials/novartis-investigational-multiple-sclerosis-therapy-gilenia-fty720-shown-reduce-relapse-rates-9139.html. Accessed April 27, 2010.
16. Inhalers containing CFCs being eliminated. Pharamacist eLink website. Available at: www.pharmacistelink.com/index.php/Drugs-and-Treatment/Inhalers-containing-CFC-s-being-eliminated.html. Accessed April 27, 2010.

New Drugs, Indications, Dosage Forms, and Approvals

• Hydromorphone extended-release tablets (Exalgo) have been approved by the FDA as a once-daily treatment for managing moderate to severe pain in opioid-tolerant patients needing continuous opioid analgesia for an extended period of time.¹ This formulation uses the OROS osmotic delivery system to control the release rate. It is a CII controlled substance and is accompanied by a comprehensive Risk Evaluation and Mitigation Strategy (REMS) to ensure that the medication’s benefits outweigh its risks.
• IMGN910 has received orphan drug status for treating Merkel cell carcinoma, a skin cancer that usually occurs on the head or neck.² It is in early-stage clinical trials.
• Immune globulin subcutaneous (human) 20% liquid (Hizentra) has been approved by the FDA as a once-weekly immunoglobulin replacement therapy for patients with primary immunodeficiency.³ It’s the first 20% subcutaneous immunoglobulin to receive FDA approval. This high-concentration product is stabilized with L-proline, a naturally occurring amino acid, which allows it to be stored at room temperature (up to 25°C [77°F]). Some adverse reactions include injection site bruising, pain, cysts, eczema, irritation, headache, cough, diarrhea, and fatigue.⁴
• Velaglucerase alfa for injection (VPRIV) has been approved by the FDA to treat adults and children with the rare genetic disorder Gaucher disease.⁵ Patients with Gaucher disease have a deficiency of the glucocerebrosidase enzyme. This enzyme prevents lipids from building up in the liver, spleen, bone marrow, and nervous system, which prevents them from working properly. VPRIV, a long-term replacement therapy, is approved for Type 1 Gaucher disease, the most common form, and is an alternative to imiglucerase (Cerezyme), which is in short supply. The most common reactions seen in clinical trials were allergic reactions, headache, dizziness, abdominal and back pain, nausea, fatigue/weakness, fever, and prolonged activated partial thromboplastin time.

Pipeline

• Betrixaban is a once-daily oral anticoagulant in Phase 2 clinical studies.⁶ Compared with warfarin in the EXPLORE-Xa study, betrixaban decreased the bleeding incidence in patients with nonvalvular atrial fibrillation or atrial flutter who had at least one stroke risk factor. The major and clinically relevant nonmajor bleeding episodes occurred less frequently in betrixaban-treated patients.
• Dabigatran etexilate is an oral anticoagulant in Phase 3 clinical trials.⁷ At the recent American College of Cardiology meeting in Ingelheim, Germany, dabigatran demonstrated consistent stroke prevention in patients with atrial fibrillation. It also reduced the number of strokes in patients with atrial fibrillation, compared with warfarin therapy. Additionally, dabigatran etexilate 110 mg and 150 mg twice daily was associated with a lower rate of major bleeding compared with warfarin in atrial fibrillation patients at low risk of stroke.
• Fentanyl sublingual spray (SL Spray) is in Phase 3 clinical trials to treat breakthrough pain in cancer patients. Sublingual administration of this product showed rapid, effective pain relief within five minutes.⁸
• Ketamine intranasal (Ereska) is a nonopioid NMDA receptor antagonist analgesic, which is undergoing Phase 3 clinical trials for managing moderate to severe acute pain.⁹ Studies have shown rapid, statistically significant relief of moderate to severe acute postoperative pain following dental surgery, following a variety of major orthopedic surgical procedures, and in cancer breakthrough pain.
• Lu AA21004 and Lu AA24530 are undergoing Phase 3 clinical trials for treating major depressive disorder (MDD).¹⁰ Lu AA21004 is a 5-HT3, 5-HT7 and 5-HT1B receptor antagonist, 5HT1A receptor agonist, and 5-HT transporter inhibitor. To date, it has shown a low propensity for drug-drug interactions and is extensively metabolized in the liver. Lu AA24530 has shown activity as a multimodal enhancer with reuptake inhibition at monoamine transporters, and having 5-HT3 and 5-HT2c receptor antagonist activity.
• Lurasidone is an atypical antipsychotic with high affinity and antagonist effects at the dopamine D2, serotonin 5-HT2, and serotonin 5-HT7 receptors.¹¹ It is a partial agonist at serotonin 5HT1A receptor. The NDA was filed for this agent Dec. 30, 2009.
• Mipomersen, an apo-B synthesis inhibitor, is in Phase 3 clinical trials for treating patients with homozygous familial hypercholesterolemia (HoFM).¹² This agent is proposed to reduce LDL-C by preventing the development of atherogenic lipids. In a study published in Lancet, mipomersen reduced LDL-C levels by an average of more than 100 mg/dL in HoFM patients.¹³
• Oxycodone/niacin (Acurox), an abuse deterrent formulation for this popular opioid, has been rejected by the FDA.¹⁴ According to the FDA and its review committee, the rejection was due to the “flushing” from the niacin, which was deemed ineffective as an abuse deterrent. In addition, the FDA said the “flushing” could be overcome by food intake or administration with over-the-counter pain relievers.
• Vilanterol/fluticasone is a combination of the inhaled corticosteroid fluticasone and the long-acting beta-agonist (LABA) vilanterol.¹⁵ It is in Phase 3 clinical trials for treating asthma. 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. FDA approves Exaglo (hydromorphone HCl) extended-release tablets. Drugs.com website. Available at: www.drugs.com/newdrugs/fda-approves-exaglo-hydromorphone-hcl-extended-release-2033.html?printable=1. Accessed April 27, 2010.
2. ImmunoGen’s skin cancer drug gets orphan drug status. Reuters website. Available at: www.reuters.com/article/idUSSGE6270L720100308. Accessed April 27, 2010.
3. CSL Behring receives FDA approval of Hizentra, first 20 percent subcutaneous immunoglobulin therapy. Drugs.com website. Available at: www.drugs.com/newdrugs/csl-behring-receives-fda-approval-hizentra-first-20-percent-subcutaneous-immunoglobulin-therapy-2037.html. Accessed April 27, 2010.
4. Petrochko C. FDA okays 20% skin-injection immunodeficiency treatment. MedPage Today website. Available at: www.medpagetoday.com/tbprint.cfm?tbid=18858. Accessed April 27, 2010.
5. Gansz Bobo E. FDA approves therapy to treat Gaucher disease. U.S. Food and Drug Administration website. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm202288.htm. Accessed April 27, 2010.
6. Portola Pharmaceuticals and Merck announce that Phase 2 study showed investigational factor Xa inhibitor, betrixaban, reduced incidence of bleeding compared to warfarin in patients with atrial fibrillation. Merck website. Available at: www.merck.com/newsroom/news-release-archive/research-and-development/2010_0315.html. Accessed April 27, 2010.
7. Dabigatran etexilate shows greater reductions than warfarin in stroke in patients with atrial fibrillation across all stroke risk groups. Beohringer Ingelheim website. Available at: www.boehringer-ingelheim.com/news/news_releases/press_releases/2010/15_march_2010.html. Accessed April 27, 2010.
8. INSYS Therapeutics, Inc. Announces Positive Phase III Efficacy Trial Results for Fentanyl Sublingual Spray. INSYS Therapeutics website. Available at: www.insysrx.com/news.htm. Accessed April 27, 2010.
9. Third party reexamination of Javelin Pharmaceuticals’ Phase III trial data for Ereska (intranasal ketamine) yields statistically significant primary endpoint. Javelin website. Available at: ir.javelinpharmaceuticals.com/releasedetail.cfm?ReleaseID=444353. Accessed April 27, 2010.
10. Lundbeck and Takeda finalise plans to initiate phase III pivotal clinical trials with Lu AA21004 and Lu AA24530. Takeda Pharmaceutical Company Limited website. Available at: www.takeda.com/press/article_35859.html. Accessed April 27, 2010.
11. Dainippon Sumitomo Pharma America announces FDA acceptance of lurasidone new drug application for treatment of schizophrenia. PR Newswire website. Available at: www.prnewswire.com/news-releases/dainippon-sumitomo-pharma-america-announces-fda-acceptance-of-lurasidone-new-drug-application-for-treatment-of-schizophrenia-87265597.html. Accessed April 27, 2010.
12. Mipomersen Phase 3 study in HoFH featured in The Lancet. Business Wire website. Available at: www.businesswire.com/portal/site/home/email/alert/?ndmViewId=news_view&newsLang=en&newsId=20100315005928. Accessed April 27, 2010.
13. Raal FJ, Santos RD, Blom DJ, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet. 2010;375(9719):998-1006.
14. US FDA panel rejects King, Acura painkiller. Reuters website. Available at: www.reuters.com/assets/print?aid=USN2223552220100422. Accessed April 27, 2010.
15. Dennis M. GlaxoSmithKline begins late-stage clinical programme for asthma drug Relovair. FirstWord website. Available at: www.firstwordplus.com/Fws.do?articleid=E256469FBD8F4A2F80C5DD3E844CC1E1&logRowId=356423. Accessed April 27, 2010.

New Drugs, Indications, Dosage Forms, and Approvals

• Hydromorphone extended-release tablets (Exalgo) have been approved by the FDA as a once-daily treatment for managing moderate to severe pain in opioid-tolerant patients needing continuous opioid analgesia for an extended period of time.¹ This formulation uses the OROS osmotic delivery system to control the release rate. It is a CII controlled substance and is accompanied by a comprehensive Risk Evaluation and Mitigation Strategy (REMS) to ensure that the medication’s benefits outweigh its risks.
• IMGN910 has received orphan drug status for treating Merkel cell carcinoma, a skin cancer that usually occurs on the head or neck.² It is in early-stage clinical trials.
• Immune globulin subcutaneous (human) 20% liquid (Hizentra) has been approved by the FDA as a once-weekly immunoglobulin replacement therapy for patients with primary immunodeficiency.³ It’s the first 20% subcutaneous immunoglobulin to receive FDA approval. This high-concentration product is stabilized with L-proline, a naturally occurring amino acid, which allows it to be stored at room temperature (up to 25°C [77°F]). Some adverse reactions include injection site bruising, pain, cysts, eczema, irritation, headache, cough, diarrhea, and fatigue.⁴
• Velaglucerase alfa for injection (VPRIV) has been approved by the FDA to treat adults and children with the rare genetic disorder Gaucher disease.⁵ Patients with Gaucher disease have a deficiency of the glucocerebrosidase enzyme. This enzyme prevents lipids from building up in the liver, spleen, bone marrow, and nervous system, which prevents them from working properly. VPRIV, a long-term replacement therapy, is approved for Type 1 Gaucher disease, the most common form, and is an alternative to imiglucerase (Cerezyme), which is in short supply. The most common reactions seen in clinical trials were allergic reactions, headache, dizziness, abdominal and back pain, nausea, fatigue/weakness, fever, and prolonged activated partial thromboplastin time.

Pipeline

• Betrixaban is a once-daily oral anticoagulant in Phase 2 clinical studies.⁶ Compared with warfarin in the EXPLORE-Xa study, betrixaban decreased the bleeding incidence in patients with nonvalvular atrial fibrillation or atrial flutter who had at least one stroke risk factor. The major and clinically relevant nonmajor bleeding episodes occurred less frequently in betrixaban-treated patients.
• Dabigatran etexilate is an oral anticoagulant in Phase 3 clinical trials.⁷ At the recent American College of Cardiology meeting in Ingelheim, Germany, dabigatran demonstrated consistent stroke prevention in patients with atrial fibrillation. It also reduced the number of strokes in patients with atrial fibrillation, compared with warfarin therapy. Additionally, dabigatran etexilate 110 mg and 150 mg twice daily was associated with a lower rate of major bleeding compared with warfarin in atrial fibrillation patients at low risk of stroke.
• Fentanyl sublingual spray (SL Spray) is in Phase 3 clinical trials to treat breakthrough pain in cancer patients. Sublingual administration of this product showed rapid, effective pain relief within five minutes.⁸
• Ketamine intranasal (Ereska) is a nonopioid NMDA receptor antagonist analgesic, which is undergoing Phase 3 clinical trials for managing moderate to severe acute pain.⁹ Studies have shown rapid, statistically significant relief of moderate to severe acute postoperative pain following dental surgery, following a variety of major orthopedic surgical procedures, and in cancer breakthrough pain.
• Lu AA21004 and Lu AA24530 are undergoing Phase 3 clinical trials for treating major depressive disorder (MDD).¹⁰ Lu AA21004 is a 5-HT3, 5-HT7 and 5-HT1B receptor antagonist, 5HT1A receptor agonist, and 5-HT transporter inhibitor. To date, it has shown a low propensity for drug-drug interactions and is extensively metabolized in the liver. Lu AA24530 has shown activity as a multimodal enhancer with reuptake inhibition at monoamine transporters, and having 5-HT3 and 5-HT2c receptor antagonist activity.
• Lurasidone is an atypical antipsychotic with high affinity and antagonist effects at the dopamine D2, serotonin 5-HT2, and serotonin 5-HT7 receptors.¹¹ It is a partial agonist at serotonin 5HT1A receptor. The NDA was filed for this agent Dec. 30, 2009.
• Mipomersen, an apo-B synthesis inhibitor, is in Phase 3 clinical trials for treating patients with homozygous familial hypercholesterolemia (HoFM).¹² This agent is proposed to reduce LDL-C by preventing the development of atherogenic lipids. In a study published in Lancet, mipomersen reduced LDL-C levels by an average of more than 100 mg/dL in HoFM patients.¹³
• Oxycodone/niacin (Acurox), an abuse deterrent formulation for this popular opioid, has been rejected by the FDA.¹⁴ According to the FDA and its review committee, the rejection was due to the “flushing” from the niacin, which was deemed ineffective as an abuse deterrent. In addition, the FDA said the “flushing” could be overcome by food intake or administration with over-the-counter pain relievers.
• Vilanterol/fluticasone is a combination of the inhaled corticosteroid fluticasone and the long-acting beta-agonist (LABA) vilanterol.¹⁵ It is in Phase 3 clinical trials for treating asthma. 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. FDA approves Exaglo (hydromorphone HCl) extended-release tablets. Drugs.com website. Available at: www.drugs.com/newdrugs/fda-approves-exaglo-hydromorphone-hcl-extended-release-2033.html?printable=1. Accessed April 27, 2010.
2. ImmunoGen’s skin cancer drug gets orphan drug status. Reuters website. Available at: www.reuters.com/article/idUSSGE6270L720100308. Accessed April 27, 2010.
3. CSL Behring receives FDA approval of Hizentra, first 20 percent subcutaneous immunoglobulin therapy. Drugs.com website. Available at: www.drugs.com/newdrugs/csl-behring-receives-fda-approval-hizentra-first-20-percent-subcutaneous-immunoglobulin-therapy-2037.html. Accessed April 27, 2010.
4. Petrochko C. FDA okays 20% skin-injection immunodeficiency treatment. MedPage Today website. Available at: www.medpagetoday.com/tbprint.cfm?tbid=18858. Accessed April 27, 2010.
5. Gansz Bobo E. FDA approves therapy to treat Gaucher disease. U.S. Food and Drug Administration website. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm202288.htm. Accessed April 27, 2010.
6. Portola Pharmaceuticals and Merck announce that Phase 2 study showed investigational factor Xa inhibitor, betrixaban, reduced incidence of bleeding compared to warfarin in patients with atrial fibrillation. Merck website. Available at: www.merck.com/newsroom/news-release-archive/research-and-development/2010_0315.html. Accessed April 27, 2010.
7. Dabigatran etexilate shows greater reductions than warfarin in stroke in patients with atrial fibrillation across all stroke risk groups. Beohringer Ingelheim website. Available at: www.boehringer-ingelheim.com/news/news_releases/press_releases/2010/15_march_2010.html. Accessed April 27, 2010.
8. INSYS Therapeutics, Inc. Announces Positive Phase III Efficacy Trial Results for Fentanyl Sublingual Spray. INSYS Therapeutics website. Available at: www.insysrx.com/news.htm. Accessed April 27, 2010.
9. Third party reexamination of Javelin Pharmaceuticals’ Phase III trial data for Ereska (intranasal ketamine) yields statistically significant primary endpoint. Javelin website. Available at: ir.javelinpharmaceuticals.com/releasedetail.cfm?ReleaseID=444353. Accessed April 27, 2010.
10. Lundbeck and Takeda finalise plans to initiate phase III pivotal clinical trials with Lu AA21004 and Lu AA24530. Takeda Pharmaceutical Company Limited website. Available at: www.takeda.com/press/article_35859.html. Accessed April 27, 2010.
11. Dainippon Sumitomo Pharma America announces FDA acceptance of lurasidone new drug application for treatment of schizophrenia. PR Newswire website. Available at: www.prnewswire.com/news-releases/dainippon-sumitomo-pharma-america-announces-fda-acceptance-of-lurasidone-new-drug-application-for-treatment-of-schizophrenia-87265597.html. Accessed April 27, 2010.
12. Mipomersen Phase 3 study in HoFH featured in The Lancet. Business Wire website. Available at: www.businesswire.com/portal/site/home/email/alert/?ndmViewId=news_view&newsLang=en&newsId=20100315005928. Accessed April 27, 2010.
13. Raal FJ, Santos RD, Blom DJ, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet. 2010;375(9719):998-1006.
14. US FDA panel rejects King, Acura painkiller. Reuters website. Available at: www.reuters.com/assets/print?aid=USN2223552220100422. Accessed April 27, 2010.
15. Dennis M. GlaxoSmithKline begins late-stage clinical programme for asthma drug Relovair. FirstWord website. Available at: www.firstwordplus.com/Fws.do?articleid=E256469FBD8F4A2F80C5DD3E844CC1E1&logRowId=356423. Accessed April 27, 2010.

New Drugs, Indications, Dosage Forms, and Approvals

• Hydromorphone extended-release tablets (Exalgo) have been approved by the FDA as a once-daily treatment for managing moderate to severe pain in opioid-tolerant patients needing continuous opioid analgesia for an extended period of time.¹ This formulation uses the OROS osmotic delivery system to control the release rate. It is a CII controlled substance and is accompanied by a comprehensive Risk Evaluation and Mitigation Strategy (REMS) to ensure that the medication’s benefits outweigh its risks.
• IMGN910 has received orphan drug status for treating Merkel cell carcinoma, a skin cancer that usually occurs on the head or neck.² It is in early-stage clinical trials.
• Immune globulin subcutaneous (human) 20% liquid (Hizentra) has been approved by the FDA as a once-weekly immunoglobulin replacement therapy for patients with primary immunodeficiency.³ It’s the first 20% subcutaneous immunoglobulin to receive FDA approval. This high-concentration product is stabilized with L-proline, a naturally occurring amino acid, which allows it to be stored at room temperature (up to 25°C [77°F]). Some adverse reactions include injection site bruising, pain, cysts, eczema, irritation, headache, cough, diarrhea, and fatigue.⁴
• Velaglucerase alfa for injection (VPRIV) has been approved by the FDA to treat adults and children with the rare genetic disorder Gaucher disease.⁵ Patients with Gaucher disease have a deficiency of the glucocerebrosidase enzyme. This enzyme prevents lipids from building up in the liver, spleen, bone marrow, and nervous system, which prevents them from working properly. VPRIV, a long-term replacement therapy, is approved for Type 1 Gaucher disease, the most common form, and is an alternative to imiglucerase (Cerezyme), which is in short supply. The most common reactions seen in clinical trials were allergic reactions, headache, dizziness, abdominal and back pain, nausea, fatigue/weakness, fever, and prolonged activated partial thromboplastin time.

Pipeline

• Betrixaban is a once-daily oral anticoagulant in Phase 2 clinical studies.⁶ Compared with warfarin in the EXPLORE-Xa study, betrixaban decreased the bleeding incidence in patients with nonvalvular atrial fibrillation or atrial flutter who had at least one stroke risk factor. The major and clinically relevant nonmajor bleeding episodes occurred less frequently in betrixaban-treated patients.
• Dabigatran etexilate is an oral anticoagulant in Phase 3 clinical trials.⁷ At the recent American College of Cardiology meeting in Ingelheim, Germany, dabigatran demonstrated consistent stroke prevention in patients with atrial fibrillation. It also reduced the number of strokes in patients with atrial fibrillation, compared with warfarin therapy. Additionally, dabigatran etexilate 110 mg and 150 mg twice daily was associated with a lower rate of major bleeding compared with warfarin in atrial fibrillation patients at low risk of stroke.
• Fentanyl sublingual spray (SL Spray) is in Phase 3 clinical trials to treat breakthrough pain in cancer patients. Sublingual administration of this product showed rapid, effective pain relief within five minutes.⁸
• Ketamine intranasal (Ereska) is a nonopioid NMDA receptor antagonist analgesic, which is undergoing Phase 3 clinical trials for managing moderate to severe acute pain.⁹ Studies have shown rapid, statistically significant relief of moderate to severe acute postoperative pain following dental surgery, following a variety of major orthopedic surgical procedures, and in cancer breakthrough pain.
• Lu AA21004 and Lu AA24530 are undergoing Phase 3 clinical trials for treating major depressive disorder (MDD).¹⁰ Lu AA21004 is a 5-HT3, 5-HT7 and 5-HT1B receptor antagonist, 5HT1A receptor agonist, and 5-HT transporter inhibitor. To date, it has shown a low propensity for drug-drug interactions and is extensively metabolized in the liver. Lu AA24530 has shown activity as a multimodal enhancer with reuptake inhibition at monoamine transporters, and having 5-HT3 and 5-HT2c receptor antagonist activity.
• Lurasidone is an atypical antipsychotic with high affinity and antagonist effects at the dopamine D2, serotonin 5-HT2, and serotonin 5-HT7 receptors.¹¹ It is a partial agonist at serotonin 5HT1A receptor. The NDA was filed for this agent Dec. 30, 2009.
• Mipomersen, an apo-B synthesis inhibitor, is in Phase 3 clinical trials for treating patients with homozygous familial hypercholesterolemia (HoFM).¹² This agent is proposed to reduce LDL-C by preventing the development of atherogenic lipids. In a study published in Lancet, mipomersen reduced LDL-C levels by an average of more than 100 mg/dL in HoFM patients.¹³
• Oxycodone/niacin (Acurox), an abuse deterrent formulation for this popular opioid, has been rejected by the FDA.¹⁴ According to the FDA and its review committee, the rejection was due to the “flushing” from the niacin, which was deemed ineffective as an abuse deterrent. In addition, the FDA said the “flushing” could be overcome by food intake or administration with over-the-counter pain relievers.
• Vilanterol/fluticasone is a combination of the inhaled corticosteroid fluticasone and the long-acting beta-agonist (LABA) vilanterol.¹⁵ It is in Phase 3 clinical trials for treating asthma. 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. FDA approves Exaglo (hydromorphone HCl) extended-release tablets. Drugs.com website. Available at: www.drugs.com/newdrugs/fda-approves-exaglo-hydromorphone-hcl-extended-release-2033.html?printable=1. Accessed April 27, 2010.
2. ImmunoGen’s skin cancer drug gets orphan drug status. Reuters website. Available at: www.reuters.com/article/idUSSGE6270L720100308. Accessed April 27, 2010.
3. CSL Behring receives FDA approval of Hizentra, first 20 percent subcutaneous immunoglobulin therapy. Drugs.com website. Available at: www.drugs.com/newdrugs/csl-behring-receives-fda-approval-hizentra-first-20-percent-subcutaneous-immunoglobulin-therapy-2037.html. Accessed April 27, 2010.
4. Petrochko C. FDA okays 20% skin-injection immunodeficiency treatment. MedPage Today website. Available at: www.medpagetoday.com/tbprint.cfm?tbid=18858. Accessed April 27, 2010.
5. Gansz Bobo E. FDA approves therapy to treat Gaucher disease. U.S. Food and Drug Administration website. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm202288.htm. Accessed April 27, 2010.
6. Portola Pharmaceuticals and Merck announce that Phase 2 study showed investigational factor Xa inhibitor, betrixaban, reduced incidence of bleeding compared to warfarin in patients with atrial fibrillation. Merck website. Available at: www.merck.com/newsroom/news-release-archive/research-and-development/2010_0315.html. Accessed April 27, 2010.
7. Dabigatran etexilate shows greater reductions than warfarin in stroke in patients with atrial fibrillation across all stroke risk groups. Beohringer Ingelheim website. Available at: www.boehringer-ingelheim.com/news/news_releases/press_releases/2010/15_march_2010.html. Accessed April 27, 2010.
8. INSYS Therapeutics, Inc. Announces Positive Phase III Efficacy Trial Results for Fentanyl Sublingual Spray. INSYS Therapeutics website. Available at: www.insysrx.com/news.htm. Accessed April 27, 2010.
9. Third party reexamination of Javelin Pharmaceuticals’ Phase III trial data for Ereska (intranasal ketamine) yields statistically significant primary endpoint. Javelin website. Available at: ir.javelinpharmaceuticals.com/releasedetail.cfm?ReleaseID=444353. Accessed April 27, 2010.
10. Lundbeck and Takeda finalise plans to initiate phase III pivotal clinical trials with Lu AA21004 and Lu AA24530. Takeda Pharmaceutical Company Limited website. Available at: www.takeda.com/press/article_35859.html. Accessed April 27, 2010.
11. Dainippon Sumitomo Pharma America announces FDA acceptance of lurasidone new drug application for treatment of schizophrenia. PR Newswire website. Available at: www.prnewswire.com/news-releases/dainippon-sumitomo-pharma-america-announces-fda-acceptance-of-lurasidone-new-drug-application-for-treatment-of-schizophrenia-87265597.html. Accessed April 27, 2010.
12. Mipomersen Phase 3 study in HoFH featured in The Lancet. Business Wire website. Available at: www.businesswire.com/portal/site/home/email/alert/?ndmViewId=news_view&newsLang=en&newsId=20100315005928. Accessed April 27, 2010.
13. Raal FJ, Santos RD, Blom DJ, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet. 2010;375(9719):998-1006.
14. US FDA panel rejects King, Acura painkiller. Reuters website. Available at: www.reuters.com/assets/print?aid=USN2223552220100422. Accessed April 27, 2010.
15. Dennis M. GlaxoSmithKline begins late-stage clinical programme for asthma drug Relovair. FirstWord website. Available at: www.firstwordplus.com/Fws.do?articleid=E256469FBD8F4A2F80C5DD3E844CC1E1&logRowId=356423. Accessed April 27, 2010.

A number of pharmaceutical agents are FDA-approved to treat different types of neuropathic pain. For example, the most recently approved agents include pregabalin (Lyrica, Pfizer) and duloxetine (Cymbalta, Eli Lilly & Company). Additionally Neurontin (gabapentin, Pfizer) and its generics have been available since the 1990s, and have also been used to treat neuropathic pain (it is specifically FDA-approved to treat post-herpetic neuralgia [PHN]).

Lyrica

In June 2005, Lyrica received FDA-approval for treatment of neuropathic pain associated with diabetic peripheral neuropathy (DPN) and PHN as well as for treatment of adults with partial onset seizures. The maximum recommended dose of Lyrica for DPN is 100mg three times daily (TID). When treating patients with a creatinine clearance (CrCL) of < 60 mL/min, initiate at a lower dose (50 mg TID) because it is primarily renally eliminated. When discontinuing Lyrica, it should be gradually tapered over a minimum of one week. The recommended dose for treatment of PHN is 75–150 mg twice daily (BID), or 50–100 mg TID for patients with a CrCL of at least 60mL/min. The dose should be reduced for patients with a CrCL < 60mL/min. If no pain relief is obtained within two to four weeks at this dose, it may be gradually increased to 600 mg/day (200 mg TID or 300 mg BID); however, side effects may be more severe because they are dose-dependent (e.g., ataxia, dizziness, dry mouth, peripheral edema, somnolence, and weight gain).

Other guidelines for dosing in renally impaired patients should be reviewed in the product labeling. Because Lyrica has been reported to cause euphoria, it has been designated as a controlled substance (C-V). There are no specific drug interactions except with the glitazones (weight gain, fluid retention, or congestive heart failure exacerbation may occur) and the possibility of additive central nervous system (CNS) effects if given with other agents that affect the CNS. Lyrica is available in the following strength capsules: 25, 50, 75, 100, 150, 200, 225, and 300mg. Head-to-head comparisons to similar agents are not available.

Cymbalta

In August 2004, the FDA approved Cymbalta for treatment of DPN and major depressive disorder (MDD). Dosing for treatment of DPN is 60 mg once daily. A lower starting dose may be used in patients with renal impairment. (It should not be used in patients with a CrCL <30 mL/min.) Common adverse effects include nausea, dizziness, somnolence, constipation, dry mouth, and increased sweating. Serum transaminase elevations have also been reported. Because Cymbalta is metabolized by CYP1A2 and CYP2D6, numerous drug interactions may occur. Drug discontinuation should be performed gradually to avoid withdrawal symptoms. Cymbalta capsules are delayed-release and are available in the following strengths: 20, 30, and 60 mg. (They should not be opened or crushed prior to administration).

Diabetic Peripheral Neuropathic Pain

Earlier this year, a Consensus Guideline on the management of diabetic peripheral neuropathic pain (DPNP) was published, the first of its kind. Treatment of DPNP may mirror other peripheral neuropathic pain syndromes, and, therefore, this guideline may assist in managing other similar patients.

A goal of 100% pain relief is ideal but often unrealistic. Many patients will only experience a 30%-50% reduction in pain relief; however, this may enable the patient to return to social activities or work and improve their quality of life. Hospitalists and other members of the healthcare team must keep in mind that the patients’ treatment goals may significantly differ from their own goals of therapy. In managing these complex patients we must bear in mind that complete pain relief may not be attainable. We must also continue to communicate with our patients and provide them with information on what is known and unknown about the mechanisms and treatment of neuropathic pain. By developing and maintaining these patient relationships, our patients will apt to be more satisfied with their treatment, even if they do not have 100% improvement.

In DPNP (there are many patients who may have this and not know that they are diabetic or may be in denial about the degree of their diabetes), it is important for the patient to play an active role in their care (e.g., glycemic control, foot care, analgesic treatment). If treatment plans are not for FDA-approved uses, obtain patient consent. Remember, patients now have access to approved labeling via the internet. If they feel that their healthcare providers are not being “above aboard,” lack of trust can significantly affect care.

Neurontin

One of the more commonly used agents to treat neuropathic syndromes is Neurontin (gabapentin). Disadvantages to the use of gabapentin include the need for dose titration and multiple daily doses. Gabapentin is a good alternative as a second-line agent for patients with DPNP who don’t respond well to or can’t tolerate first-line agents (approved agents or others with evidence: e.g., oxycodone controlled-release, tricyclic antidepressants, Lyrica, Cymbalta).

It is recommended that treatment is begun using a first-line agent. Then each time you evaluate the patient, ask them whether the pain is worse or whether the nature of the pain has changed. They should also be asked if they are experiencing any adverse effects. The agent should be titrated to the maximum tolerated dose with an expected goal of at least 50% pain reduction from baseline. Some pain improvement should be expected within three weeks of therapy initiation. Therefore ascertain that this is followed upon hospital discharge. If no improvement is noted within three weeks, modification of therapy may be warranted.

If the patient derives some (but not optimal) therapy benefit without adverse effects, consider adding a second agent. The agent can be another first-line agent or a second-line agent. Consider rational pharmacotherapy (e.g., avoid additive side effects, consider synergy of agents, avoid drug interactions), and use an agent with a different mechanism of action.

If the patient is receiving no benefit from the current therapy or they are experiencing intolerable adverse effects, consider changing to another agent with a different mechanism of action. If the current agent is Cymbalta, Lyrica, or Neurontin (and the patient has no risk of seizures), taper the drug off over at least one week. When starting a new treatment, always take into consideration the patient’s medical and psychiatric comorbidities, any potential contraindications, and other factors such as the potential for drug interactions, side effects (e.g., weight gain, edema), and/or cost.

Topical therapies may also provide some benefit to the patient with neuropathic pain syndromes (e.g., capsaicin, lidocaine 5% patch). Remember that a specialist can always be consulted for expert advice or for difficult-to-manage patients. TH

Michele B. Kaufman is a drug information specialist and a medical writer based in New York City.

References

1. Neurontin (gabapentin) [package insert]. New York: Pfizer Inc;. December 2005.
2. Lyrica (pregabalin) [package insert]. New York: Pfizer Inc; March 2006.
3. Cymbalta (duloxetine) [package insert]. Indianapolis: Eli Lilly and Company; December 14, 2005.
4. The Medical Letter on Drugs and Therapeutics. Duloxetine; Volume 47 (Issue 1215/1216), August 15/29, 2005; 67-68.
5. Pregabalin. The Medical Letter on Drugs and Therapeutics. 47(1217) :75-77. Available online at www.medletter.com/restricted/articles/w1217b.pdf. Last accessed on July 28, 2006.
6. Facts and Comparisons Updated Monthly. Wolters Kluwer Health: October 2005.
7. Thomson Micromedex Healthcare Series: Document Comparison of Pregabalin and Gabapentin. Available at: www.thomsonhc.com/hcs/librarian/PFDefaultActionId/pf.PrintReady. Last accessed June 7, 2006.
8. Argoff CE, Backonia M-M, Belgrade ML, et al. Consensus Guidelines: treatment planning and options. Mayo Clin Proc. 2006;81(4):S12-S25.
9. Argoff CE, Cole BE, Fishbain DA, et al. Diabetic Peripheral neuropathic pain: clinical and quality-of-life issues. Mayo Clin Proc. 2006;81(4, suppl):S3-S11.
10. Belgrade ML, Cole BE, McCarberg BH, et al. Diabetic peripheral neuropathic pain: case studies. Mayo Clin Proc. 2006 Apr;81(4 Suppl):S26-S32.

A number of pharmaceutical agents are FDA-approved to treat different types of neuropathic pain. For example, the most recently approved agents include pregabalin (Lyrica, Pfizer) and duloxetine (Cymbalta, Eli Lilly & Company). Additionally Neurontin (gabapentin, Pfizer) and its generics have been available since the 1990s, and have also been used to treat neuropathic pain (it is specifically FDA-approved to treat post-herpetic neuralgia [PHN]).

Lyrica

In June 2005, Lyrica received FDA-approval for treatment of neuropathic pain associated with diabetic peripheral neuropathy (DPN) and PHN as well as for treatment of adults with partial onset seizures. The maximum recommended dose of Lyrica for DPN is 100mg three times daily (TID). When treating patients with a creatinine clearance (CrCL) of < 60 mL/min, initiate at a lower dose (50 mg TID) because it is primarily renally eliminated. When discontinuing Lyrica, it should be gradually tapered over a minimum of one week. The recommended dose for treatment of PHN is 75–150 mg twice daily (BID), or 50–100 mg TID for patients with a CrCL of at least 60mL/min. The dose should be reduced for patients with a CrCL < 60mL/min. If no pain relief is obtained within two to four weeks at this dose, it may be gradually increased to 600 mg/day (200 mg TID or 300 mg BID); however, side effects may be more severe because they are dose-dependent (e.g., ataxia, dizziness, dry mouth, peripheral edema, somnolence, and weight gain).

Other guidelines for dosing in renally impaired patients should be reviewed in the product labeling. Because Lyrica has been reported to cause euphoria, it has been designated as a controlled substance (C-V). There are no specific drug interactions except with the glitazones (weight gain, fluid retention, or congestive heart failure exacerbation may occur) and the possibility of additive central nervous system (CNS) effects if given with other agents that affect the CNS. Lyrica is available in the following strength capsules: 25, 50, 75, 100, 150, 200, 225, and 300mg. Head-to-head comparisons to similar agents are not available.

Cymbalta

In August 2004, the FDA approved Cymbalta for treatment of DPN and major depressive disorder (MDD). Dosing for treatment of DPN is 60 mg once daily. A lower starting dose may be used in patients with renal impairment. (It should not be used in patients with a CrCL <30 mL/min.) Common adverse effects include nausea, dizziness, somnolence, constipation, dry mouth, and increased sweating. Serum transaminase elevations have also been reported. Because Cymbalta is metabolized by CYP1A2 and CYP2D6, numerous drug interactions may occur. Drug discontinuation should be performed gradually to avoid withdrawal symptoms. Cymbalta capsules are delayed-release and are available in the following strengths: 20, 30, and 60 mg. (They should not be opened or crushed prior to administration).

Diabetic Peripheral Neuropathic Pain

Earlier this year, a Consensus Guideline on the management of diabetic peripheral neuropathic pain (DPNP) was published, the first of its kind. Treatment of DPNP may mirror other peripheral neuropathic pain syndromes, and, therefore, this guideline may assist in managing other similar patients.

A goal of 100% pain relief is ideal but often unrealistic. Many patients will only experience a 30%-50% reduction in pain relief; however, this may enable the patient to return to social activities or work and improve their quality of life. Hospitalists and other members of the healthcare team must keep in mind that the patients’ treatment goals may significantly differ from their own goals of therapy. In managing these complex patients we must bear in mind that complete pain relief may not be attainable. We must also continue to communicate with our patients and provide them with information on what is known and unknown about the mechanisms and treatment of neuropathic pain. By developing and maintaining these patient relationships, our patients will apt to be more satisfied with their treatment, even if they do not have 100% improvement.

In DPNP (there are many patients who may have this and not know that they are diabetic or may be in denial about the degree of their diabetes), it is important for the patient to play an active role in their care (e.g., glycemic control, foot care, analgesic treatment). If treatment plans are not for FDA-approved uses, obtain patient consent. Remember, patients now have access to approved labeling via the internet. If they feel that their healthcare providers are not being “above aboard,” lack of trust can significantly affect care.

Neurontin

One of the more commonly used agents to treat neuropathic syndromes is Neurontin (gabapentin). Disadvantages to the use of gabapentin include the need for dose titration and multiple daily doses. Gabapentin is a good alternative as a second-line agent for patients with DPNP who don’t respond well to or can’t tolerate first-line agents (approved agents or others with evidence: e.g., oxycodone controlled-release, tricyclic antidepressants, Lyrica, Cymbalta).

It is recommended that treatment is begun using a first-line agent. Then each time you evaluate the patient, ask them whether the pain is worse or whether the nature of the pain has changed. They should also be asked if they are experiencing any adverse effects. The agent should be titrated to the maximum tolerated dose with an expected goal of at least 50% pain reduction from baseline. Some pain improvement should be expected within three weeks of therapy initiation. Therefore ascertain that this is followed upon hospital discharge. If no improvement is noted within three weeks, modification of therapy may be warranted.

If the patient derives some (but not optimal) therapy benefit without adverse effects, consider adding a second agent. The agent can be another first-line agent or a second-line agent. Consider rational pharmacotherapy (e.g., avoid additive side effects, consider synergy of agents, avoid drug interactions), and use an agent with a different mechanism of action.

If the patient is receiving no benefit from the current therapy or they are experiencing intolerable adverse effects, consider changing to another agent with a different mechanism of action. If the current agent is Cymbalta, Lyrica, or Neurontin (and the patient has no risk of seizures), taper the drug off over at least one week. When starting a new treatment, always take into consideration the patient’s medical and psychiatric comorbidities, any potential contraindications, and other factors such as the potential for drug interactions, side effects (e.g., weight gain, edema), and/or cost.

Topical therapies may also provide some benefit to the patient with neuropathic pain syndromes (e.g., capsaicin, lidocaine 5% patch). Remember that a specialist can always be consulted for expert advice or for difficult-to-manage patients. TH

Michele B. Kaufman is a drug information specialist and a medical writer based in New York City.

References

1. Neurontin (gabapentin) [package insert]. New York: Pfizer Inc;. December 2005.
2. Lyrica (pregabalin) [package insert]. New York: Pfizer Inc; March 2006.
3. Cymbalta (duloxetine) [package insert]. Indianapolis: Eli Lilly and Company; December 14, 2005.
4. The Medical Letter on Drugs and Therapeutics. Duloxetine; Volume 47 (Issue 1215/1216), August 15/29, 2005; 67-68.
5. Pregabalin. The Medical Letter on Drugs and Therapeutics. 47(1217) :75-77. Available online at www.medletter.com/restricted/articles/w1217b.pdf. Last accessed on July 28, 2006.
6. Facts and Comparisons Updated Monthly. Wolters Kluwer Health: October 2005.
7. Thomson Micromedex Healthcare Series: Document Comparison of Pregabalin and Gabapentin. Available at: www.thomsonhc.com/hcs/librarian/PFDefaultActionId/pf.PrintReady. Last accessed June 7, 2006.
8. Argoff CE, Backonia M-M, Belgrade ML, et al. Consensus Guidelines: treatment planning and options. Mayo Clin Proc. 2006;81(4):S12-S25.
9. Argoff CE, Cole BE, Fishbain DA, et al. Diabetic Peripheral neuropathic pain: clinical and quality-of-life issues. Mayo Clin Proc. 2006;81(4, suppl):S3-S11.
10. Belgrade ML, Cole BE, McCarberg BH, et al. Diabetic peripheral neuropathic pain: case studies. Mayo Clin Proc. 2006 Apr;81(4 Suppl):S26-S32.

A number of pharmaceutical agents are FDA-approved to treat different types of neuropathic pain. For example, the most recently approved agents include pregabalin (Lyrica, Pfizer) and duloxetine (Cymbalta, Eli Lilly & Company). Additionally Neurontin (gabapentin, Pfizer) and its generics have been available since the 1990s, and have also been used to treat neuropathic pain (it is specifically FDA-approved to treat post-herpetic neuralgia [PHN]).

Lyrica

In June 2005, Lyrica received FDA-approval for treatment of neuropathic pain associated with diabetic peripheral neuropathy (DPN) and PHN as well as for treatment of adults with partial onset seizures. The maximum recommended dose of Lyrica for DPN is 100mg three times daily (TID). When treating patients with a creatinine clearance (CrCL) of < 60 mL/min, initiate at a lower dose (50 mg TID) because it is primarily renally eliminated. When discontinuing Lyrica, it should be gradually tapered over a minimum of one week. The recommended dose for treatment of PHN is 75–150 mg twice daily (BID), or 50–100 mg TID for patients with a CrCL of at least 60mL/min. The dose should be reduced for patients with a CrCL < 60mL/min. If no pain relief is obtained within two to four weeks at this dose, it may be gradually increased to 600 mg/day (200 mg TID or 300 mg BID); however, side effects may be more severe because they are dose-dependent (e.g., ataxia, dizziness, dry mouth, peripheral edema, somnolence, and weight gain).

Other guidelines for dosing in renally impaired patients should be reviewed in the product labeling. Because Lyrica has been reported to cause euphoria, it has been designated as a controlled substance (C-V). There are no specific drug interactions except with the glitazones (weight gain, fluid retention, or congestive heart failure exacerbation may occur) and the possibility of additive central nervous system (CNS) effects if given with other agents that affect the CNS. Lyrica is available in the following strength capsules: 25, 50, 75, 100, 150, 200, 225, and 300mg. Head-to-head comparisons to similar agents are not available.

Cymbalta

In August 2004, the FDA approved Cymbalta for treatment of DPN and major depressive disorder (MDD). Dosing for treatment of DPN is 60 mg once daily. A lower starting dose may be used in patients with renal impairment. (It should not be used in patients with a CrCL <30 mL/min.) Common adverse effects include nausea, dizziness, somnolence, constipation, dry mouth, and increased sweating. Serum transaminase elevations have also been reported. Because Cymbalta is metabolized by CYP1A2 and CYP2D6, numerous drug interactions may occur. Drug discontinuation should be performed gradually to avoid withdrawal symptoms. Cymbalta capsules are delayed-release and are available in the following strengths: 20, 30, and 60 mg. (They should not be opened or crushed prior to administration).

Diabetic Peripheral Neuropathic Pain

Earlier this year, a Consensus Guideline on the management of diabetic peripheral neuropathic pain (DPNP) was published, the first of its kind. Treatment of DPNP may mirror other peripheral neuropathic pain syndromes, and, therefore, this guideline may assist in managing other similar patients.

A goal of 100% pain relief is ideal but often unrealistic. Many patients will only experience a 30%-50% reduction in pain relief; however, this may enable the patient to return to social activities or work and improve their quality of life. Hospitalists and other members of the healthcare team must keep in mind that the patients’ treatment goals may significantly differ from their own goals of therapy. In managing these complex patients we must bear in mind that complete pain relief may not be attainable. We must also continue to communicate with our patients and provide them with information on what is known and unknown about the mechanisms and treatment of neuropathic pain. By developing and maintaining these patient relationships, our patients will apt to be more satisfied with their treatment, even if they do not have 100% improvement.

In DPNP (there are many patients who may have this and not know that they are diabetic or may be in denial about the degree of their diabetes), it is important for the patient to play an active role in their care (e.g., glycemic control, foot care, analgesic treatment). If treatment plans are not for FDA-approved uses, obtain patient consent. Remember, patients now have access to approved labeling via the internet. If they feel that their healthcare providers are not being “above aboard,” lack of trust can significantly affect care.

Neurontin

One of the more commonly used agents to treat neuropathic syndromes is Neurontin (gabapentin). Disadvantages to the use of gabapentin include the need for dose titration and multiple daily doses. Gabapentin is a good alternative as a second-line agent for patients with DPNP who don’t respond well to or can’t tolerate first-line agents (approved agents or others with evidence: e.g., oxycodone controlled-release, tricyclic antidepressants, Lyrica, Cymbalta).

It is recommended that treatment is begun using a first-line agent. Then each time you evaluate the patient, ask them whether the pain is worse or whether the nature of the pain has changed. They should also be asked if they are experiencing any adverse effects. The agent should be titrated to the maximum tolerated dose with an expected goal of at least 50% pain reduction from baseline. Some pain improvement should be expected within three weeks of therapy initiation. Therefore ascertain that this is followed upon hospital discharge. If no improvement is noted within three weeks, modification of therapy may be warranted.

If the patient derives some (but not optimal) therapy benefit without adverse effects, consider adding a second agent. The agent can be another first-line agent or a second-line agent. Consider rational pharmacotherapy (e.g., avoid additive side effects, consider synergy of agents, avoid drug interactions), and use an agent with a different mechanism of action.

If the patient is receiving no benefit from the current therapy or they are experiencing intolerable adverse effects, consider changing to another agent with a different mechanism of action. If the current agent is Cymbalta, Lyrica, or Neurontin (and the patient has no risk of seizures), taper the drug off over at least one week. When starting a new treatment, always take into consideration the patient’s medical and psychiatric comorbidities, any potential contraindications, and other factors such as the potential for drug interactions, side effects (e.g., weight gain, edema), and/or cost.

Topical therapies may also provide some benefit to the patient with neuropathic pain syndromes (e.g., capsaicin, lidocaine 5% patch). Remember that a specialist can always be consulted for expert advice or for difficult-to-manage patients. TH

Michele B. Kaufman is a drug information specialist and a medical writer based in New York City.

References

1. Neurontin (gabapentin) [package insert]. New York: Pfizer Inc;. December 2005.
2. Lyrica (pregabalin) [package insert]. New York: Pfizer Inc; March 2006.
3. Cymbalta (duloxetine) [package insert]. Indianapolis: Eli Lilly and Company; December 14, 2005.
4. The Medical Letter on Drugs and Therapeutics. Duloxetine; Volume 47 (Issue 1215/1216), August 15/29, 2005; 67-68.
5. Pregabalin. The Medical Letter on Drugs and Therapeutics. 47(1217) :75-77. Available online at www.medletter.com/restricted/articles/w1217b.pdf. Last accessed on July 28, 2006.
6. Facts and Comparisons Updated Monthly. Wolters Kluwer Health: October 2005.
7. Thomson Micromedex Healthcare Series: Document Comparison of Pregabalin and Gabapentin. Available at: www.thomsonhc.com/hcs/librarian/PFDefaultActionId/pf.PrintReady. Last accessed June 7, 2006.
8. Argoff CE, Backonia M-M, Belgrade ML, et al. Consensus Guidelines: treatment planning and options. Mayo Clin Proc. 2006;81(4):S12-S25.
9. Argoff CE, Cole BE, Fishbain DA, et al. Diabetic Peripheral neuropathic pain: clinical and quality-of-life issues. Mayo Clin Proc. 2006;81(4, suppl):S3-S11.
10. Belgrade ML, Cole BE, McCarberg BH, et al. Diabetic peripheral neuropathic pain: case studies. Mayo Clin Proc. 2006 Apr;81(4 Suppl):S26-S32.

Two new insulin products were recently FDA-approved, Exubera (inhaled human insulin, Pfizer/Nektar) and Levemir (insulin detemir, Novo Nordisk). These new insulins are important to hospitalists because admitted patients may be receiving them, patients may ask about them, and other members of the healthcare team may have questions, as well.

Nektar Therapeutics has been developing noninvasive macromolecules for inhaled delivery systems for many years. To develop Exubera (their first FDA-approved product), they collaborated with Pfizer and Sanofi-Aventis. Other Nektar products are not as far along in the U.S. drug approval process.

Exubera (inhalation powder, insulin human) was FDA-approved on January 27, 2006, and is expected to be on pharmacy shelves in June or July of this year. Exubera was also recently approved in Europe but is not available there yet, either. Exubera is short-acting and was approved for use in Types 1 and 2 diabetes mellitus in conjunction with oral agents, or with a basal insulin for basal/bolus dosing.

Peak Exubera levels occur in ~49 minutes (range 30-90 minutes) compared with regular insulin with a peak in 105 minutes (range, 60-240 minutes). In an open-label, 12-week, randomized, controlled trial Exubera improved glycemic control when substituted for or added to oral combination therapy (n=309) in adult Type 2 diabetes patients. There was a small decrease in HbA1c of ~1.4% in the Exubera-treated monotherapy patients. When Exubera was combined with two oral agents (an insulin sensitizer and a secretagogue), the HbA1c decreased ~1.9%. Patients who used only oral agents had an insignificant decrease in HbA1c (0.2%).

Investigators offered Types 1 and 2 diabetics open-label use of inhaled insulin for up to four years. The patients have maintained long-term glycemic control.

The Exubera inhaler device weighs 4 ounces and is about the size of a closed eyeglass case. Carrying the device may be problematic for some because of its size. Common side effects include cough, shortness of breath, sore throat, dry mouth, and hypoglycemia. Exubera is not recommended for 1) patients who have recently quit smoking (within six months); 2) current smokers; 3) asthmatics; or 4) those with bronchitis or emphysema.

Because Exubera is a new product that has not been available in other countries, its long-term safety is unknown. Pfizer is, however, committed to long-term safety and efficacy studies. Monitoring parameters specific to Exubera include: 1) baseline pulmonary function tests (PFTs); and 2) follow-up PFTs every six-12 months until more is known about the drug’s pulmonary safety.

The Word on the Street

Exubera’s manufacturers will likely target this agent to the population that will provide them with the greatest market potential (largest profit). Likely candidates will be those with poorly controlled diabetes on >2 oral agents; these patients will likely need more than another oral agent to improve their glycemic control. Pfizer may choose to market Exubera against insulin sensitizers such as rosiglitazone or pioglitazone —especially when it comes to pharmacoeconomics because the ‘glitazones are not yet available generically and are thus higher cost items.

Ease of use for Exubera versus injected insulin may be the sole advantage for this new agent. Some say that if Exubera is used as a tool for diabetics to get insulin treatment earlier (versus injected insulin), diabetic complications may be minimized; however, medication compliance will play a large role. The medical literature is full of articles regarding non-compliance/non-adherence with asthma inhalers, including improper inhaler use and non-use of these devices. So unless inhaled insulin can significantly improve outcomes compared with the inexpensive injections and other available therapies (e.g., insulin sensitizers), its place on health-system formularies may be limited at best.

Another Inhaled Option

Novo Nordisk received initial FDA approval for its long-acting, basal insulin analog—insulin detemir—on June 17, 2005. Subsequent approval for use in the pediatric population came on October 20, 2005. Levemir is expected on U.S. pharmacy shelves any day. Levemir has been approved in 53 countries worldwide, and has been available in Europe since March 2004.

Levemir is a basal insulin, similar to Lantus (glargine, Sanofi-Aventis), and is approved for use in adults with Types 1 and 2 diabetes and in children with Type 1 diabetes.

It is recommended that Levemir be dosed once- or twice-daily subcutaneously. Pharmacokinetically Levemir has a relatively flat action profile with a mean duration of action ranging between 5.7–23.2 hours (data from clinical trials). Following subcutaneous administration, insulin detemir has a slower, more prolonged absorption over 24 hours compared with NPH insulin. Maximum serum concentrations occur within six to eight hours following administration.

A common side effect of insulin therapies is hypoglycemia. Other side effects common to human insulins include allergic reactions, injection site reactions, lipodystrophy, pruritus, and rash. A beneficial effect obtained in some of the Levemir clinical studies was weight loss (0.2 to 0.3-kg), which occurred in several Type 1 patients. Comparatively, the Type 1 patients who received NPH insulin noted weight gain (0.4 to 1.4-kg) over the six-12 month timeframe.

There are no specific monitoring parameters for insulin detemir, except for general management of the diabetic patient (e.g., fasting blood sugar, glycosylated hemoglobin, eye exam, podiatry).

At its launch, insulin detemir will be available in 10mL vials as well as in the Levemir FlexPen. The FlexPen will require the use of NovoFine 30- or 31-gauge disposable needles. TH

Michele Kaufman is based in New York City.

References—Exubera

• Hollander PA, Blonde L, Rowe R, et al. Efficacy and safety of inhaled insulin (Exubera) compared with subcutaneous insulin therapy in patients with Type 2 diabetes: Results of a 6-month, randomized, comparative trial. Diabetes Care. 2004;27:2356-2362.
• Skyler JS, Weinstock RS, Raskin P, et al. The Inhaled Insulin Phase III Type 1 Diabetes Study Group. Use of inhaled insulin in a basal/bolus insulin regimen in Type 1 diabetic subjects: a 6-month, randomized, comparative trial. Diabetes Care. 2005 Jul:28(7):1630-1635.
• Rosenstock J, Zinman B, Murphy LJ, et al. Inhaled insulin improves glycemic control when substituted for or added to oral combination therapy in Type 2 Diabetes—a randomized, controlled trial. Ann Intern Med. 2005 Oct 18;143(8):549-588.
• The Pink Sheet, February 14, 2006; Volume 68, Number 7.Available at www.fda.gov/bbs/topics/news/2006/NEW01304.html. Last accessed March 8, 2006.

References—Levemir

• Levemir (insulin detemir [rDNA origin] injection) package insert. Novo Nordisk, Inc. Princeton, NJ; October 2005.
• Goldman JD, Lee KW. Insulin detemir—a new basal insulin analog. nn Pharmacother. 2005;39:502-507.
• Home P, Bartley P, Russell-Jones D, et al. Insulin detemir offers improved glycemic control compared with NPH insulin in people with Type 1 diabetes—a randomized clinical trial. Diabetes Care. 2004;27:1081-1087. Available at http://press.novonordisk-us.com/internal.aspx?rid=318. Last accessed March 1, 2006.

Two new insulin products were recently FDA-approved, Exubera (inhaled human insulin, Pfizer/Nektar) and Levemir (insulin detemir, Novo Nordisk). These new insulins are important to hospitalists because admitted patients may be receiving them, patients may ask about them, and other members of the healthcare team may have questions, as well.

Nektar Therapeutics has been developing noninvasive macromolecules for inhaled delivery systems for many years. To develop Exubera (their first FDA-approved product), they collaborated with Pfizer and Sanofi-Aventis. Other Nektar products are not as far along in the U.S. drug approval process.

Exubera (inhalation powder, insulin human) was FDA-approved on January 27, 2006, and is expected to be on pharmacy shelves in June or July of this year. Exubera was also recently approved in Europe but is not available there yet, either. Exubera is short-acting and was approved for use in Types 1 and 2 diabetes mellitus in conjunction with oral agents, or with a basal insulin for basal/bolus dosing.

Peak Exubera levels occur in ~49 minutes (range 30-90 minutes) compared with regular insulin with a peak in 105 minutes (range, 60-240 minutes). In an open-label, 12-week, randomized, controlled trial Exubera improved glycemic control when substituted for or added to oral combination therapy (n=309) in adult Type 2 diabetes patients. There was a small decrease in HbA1c of ~1.4% in the Exubera-treated monotherapy patients. When Exubera was combined with two oral agents (an insulin sensitizer and a secretagogue), the HbA1c decreased ~1.9%. Patients who used only oral agents had an insignificant decrease in HbA1c (0.2%).

Investigators offered Types 1 and 2 diabetics open-label use of inhaled insulin for up to four years. The patients have maintained long-term glycemic control.

The Exubera inhaler device weighs 4 ounces and is about the size of a closed eyeglass case. Carrying the device may be problematic for some because of its size. Common side effects include cough, shortness of breath, sore throat, dry mouth, and hypoglycemia. Exubera is not recommended for 1) patients who have recently quit smoking (within six months); 2) current smokers; 3) asthmatics; or 4) those with bronchitis or emphysema.

Because Exubera is a new product that has not been available in other countries, its long-term safety is unknown. Pfizer is, however, committed to long-term safety and efficacy studies. Monitoring parameters specific to Exubera include: 1) baseline pulmonary function tests (PFTs); and 2) follow-up PFTs every six-12 months until more is known about the drug’s pulmonary safety.

The Word on the Street

Exubera’s manufacturers will likely target this agent to the population that will provide them with the greatest market potential (largest profit). Likely candidates will be those with poorly controlled diabetes on >2 oral agents; these patients will likely need more than another oral agent to improve their glycemic control. Pfizer may choose to market Exubera against insulin sensitizers such as rosiglitazone or pioglitazone —especially when it comes to pharmacoeconomics because the ‘glitazones are not yet available generically and are thus higher cost items.

Ease of use for Exubera versus injected insulin may be the sole advantage for this new agent. Some say that if Exubera is used as a tool for diabetics to get insulin treatment earlier (versus injected insulin), diabetic complications may be minimized; however, medication compliance will play a large role. The medical literature is full of articles regarding non-compliance/non-adherence with asthma inhalers, including improper inhaler use and non-use of these devices. So unless inhaled insulin can significantly improve outcomes compared with the inexpensive injections and other available therapies (e.g., insulin sensitizers), its place on health-system formularies may be limited at best.

Another Inhaled Option

Novo Nordisk received initial FDA approval for its long-acting, basal insulin analog—insulin detemir—on June 17, 2005. Subsequent approval for use in the pediatric population came on October 20, 2005. Levemir is expected on U.S. pharmacy shelves any day. Levemir has been approved in 53 countries worldwide, and has been available in Europe since March 2004.

Levemir is a basal insulin, similar to Lantus (glargine, Sanofi-Aventis), and is approved for use in adults with Types 1 and 2 diabetes and in children with Type 1 diabetes.

It is recommended that Levemir be dosed once- or twice-daily subcutaneously. Pharmacokinetically Levemir has a relatively flat action profile with a mean duration of action ranging between 5.7–23.2 hours (data from clinical trials). Following subcutaneous administration, insulin detemir has a slower, more prolonged absorption over 24 hours compared with NPH insulin. Maximum serum concentrations occur within six to eight hours following administration.

A common side effect of insulin therapies is hypoglycemia. Other side effects common to human insulins include allergic reactions, injection site reactions, lipodystrophy, pruritus, and rash. A beneficial effect obtained in some of the Levemir clinical studies was weight loss (0.2 to 0.3-kg), which occurred in several Type 1 patients. Comparatively, the Type 1 patients who received NPH insulin noted weight gain (0.4 to 1.4-kg) over the six-12 month timeframe.

There are no specific monitoring parameters for insulin detemir, except for general management of the diabetic patient (e.g., fasting blood sugar, glycosylated hemoglobin, eye exam, podiatry).

At its launch, insulin detemir will be available in 10mL vials as well as in the Levemir FlexPen. The FlexPen will require the use of NovoFine 30- or 31-gauge disposable needles. TH

Michele Kaufman is based in New York City.

References—Exubera

• Hollander PA, Blonde L, Rowe R, et al. Efficacy and safety of inhaled insulin (Exubera) compared with subcutaneous insulin therapy in patients with Type 2 diabetes: Results of a 6-month, randomized, comparative trial. Diabetes Care. 2004;27:2356-2362.
• Skyler JS, Weinstock RS, Raskin P, et al. The Inhaled Insulin Phase III Type 1 Diabetes Study Group. Use of inhaled insulin in a basal/bolus insulin regimen in Type 1 diabetic subjects: a 6-month, randomized, comparative trial. Diabetes Care. 2005 Jul:28(7):1630-1635.
• Rosenstock J, Zinman B, Murphy LJ, et al. Inhaled insulin improves glycemic control when substituted for or added to oral combination therapy in Type 2 Diabetes—a randomized, controlled trial. Ann Intern Med. 2005 Oct 18;143(8):549-588.
• The Pink Sheet, February 14, 2006; Volume 68, Number 7.Available at www.fda.gov/bbs/topics/news/2006/NEW01304.html. Last accessed March 8, 2006.

References—Levemir

• Levemir (insulin detemir [rDNA origin] injection) package insert. Novo Nordisk, Inc. Princeton, NJ; October 2005.
• Goldman JD, Lee KW. Insulin detemir—a new basal insulin analog. nn Pharmacother. 2005;39:502-507.
• Home P, Bartley P, Russell-Jones D, et al. Insulin detemir offers improved glycemic control compared with NPH insulin in people with Type 1 diabetes—a randomized clinical trial. Diabetes Care. 2004;27:1081-1087. Available at http://press.novonordisk-us.com/internal.aspx?rid=318. Last accessed March 1, 2006.

Two new insulin products were recently FDA-approved, Exubera (inhaled human insulin, Pfizer/Nektar) and Levemir (insulin detemir, Novo Nordisk). These new insulins are important to hospitalists because admitted patients may be receiving them, patients may ask about them, and other members of the healthcare team may have questions, as well.

Nektar Therapeutics has been developing noninvasive macromolecules for inhaled delivery systems for many years. To develop Exubera (their first FDA-approved product), they collaborated with Pfizer and Sanofi-Aventis. Other Nektar products are not as far along in the U.S. drug approval process.

Exubera (inhalation powder, insulin human) was FDA-approved on January 27, 2006, and is expected to be on pharmacy shelves in June or July of this year. Exubera was also recently approved in Europe but is not available there yet, either. Exubera is short-acting and was approved for use in Types 1 and 2 diabetes mellitus in conjunction with oral agents, or with a basal insulin for basal/bolus dosing.

Peak Exubera levels occur in ~49 minutes (range 30-90 minutes) compared with regular insulin with a peak in 105 minutes (range, 60-240 minutes). In an open-label, 12-week, randomized, controlled trial Exubera improved glycemic control when substituted for or added to oral combination therapy (n=309) in adult Type 2 diabetes patients. There was a small decrease in HbA1c of ~1.4% in the Exubera-treated monotherapy patients. When Exubera was combined with two oral agents (an insulin sensitizer and a secretagogue), the HbA1c decreased ~1.9%. Patients who used only oral agents had an insignificant decrease in HbA1c (0.2%).

Investigators offered Types 1 and 2 diabetics open-label use of inhaled insulin for up to four years. The patients have maintained long-term glycemic control.

The Exubera inhaler device weighs 4 ounces and is about the size of a closed eyeglass case. Carrying the device may be problematic for some because of its size. Common side effects include cough, shortness of breath, sore throat, dry mouth, and hypoglycemia. Exubera is not recommended for 1) patients who have recently quit smoking (within six months); 2) current smokers; 3) asthmatics; or 4) those with bronchitis or emphysema.

Because Exubera is a new product that has not been available in other countries, its long-term safety is unknown. Pfizer is, however, committed to long-term safety and efficacy studies. Monitoring parameters specific to Exubera include: 1) baseline pulmonary function tests (PFTs); and 2) follow-up PFTs every six-12 months until more is known about the drug’s pulmonary safety.

The Word on the Street

Exubera’s manufacturers will likely target this agent to the population that will provide them with the greatest market potential (largest profit). Likely candidates will be those with poorly controlled diabetes on >2 oral agents; these patients will likely need more than another oral agent to improve their glycemic control. Pfizer may choose to market Exubera against insulin sensitizers such as rosiglitazone or pioglitazone —especially when it comes to pharmacoeconomics because the ‘glitazones are not yet available generically and are thus higher cost items.

Ease of use for Exubera versus injected insulin may be the sole advantage for this new agent. Some say that if Exubera is used as a tool for diabetics to get insulin treatment earlier (versus injected insulin), diabetic complications may be minimized; however, medication compliance will play a large role. The medical literature is full of articles regarding non-compliance/non-adherence with asthma inhalers, including improper inhaler use and non-use of these devices. So unless inhaled insulin can significantly improve outcomes compared with the inexpensive injections and other available therapies (e.g., insulin sensitizers), its place on health-system formularies may be limited at best.

Another Inhaled Option

Novo Nordisk received initial FDA approval for its long-acting, basal insulin analog—insulin detemir—on June 17, 2005. Subsequent approval for use in the pediatric population came on October 20, 2005. Levemir is expected on U.S. pharmacy shelves any day. Levemir has been approved in 53 countries worldwide, and has been available in Europe since March 2004.

Levemir is a basal insulin, similar to Lantus (glargine, Sanofi-Aventis), and is approved for use in adults with Types 1 and 2 diabetes and in children with Type 1 diabetes.

It is recommended that Levemir be dosed once- or twice-daily subcutaneously. Pharmacokinetically Levemir has a relatively flat action profile with a mean duration of action ranging between 5.7–23.2 hours (data from clinical trials). Following subcutaneous administration, insulin detemir has a slower, more prolonged absorption over 24 hours compared with NPH insulin. Maximum serum concentrations occur within six to eight hours following administration.

A common side effect of insulin therapies is hypoglycemia. Other side effects common to human insulins include allergic reactions, injection site reactions, lipodystrophy, pruritus, and rash. A beneficial effect obtained in some of the Levemir clinical studies was weight loss (0.2 to 0.3-kg), which occurred in several Type 1 patients. Comparatively, the Type 1 patients who received NPH insulin noted weight gain (0.4 to 1.4-kg) over the six-12 month timeframe.

There are no specific monitoring parameters for insulin detemir, except for general management of the diabetic patient (e.g., fasting blood sugar, glycosylated hemoglobin, eye exam, podiatry).

At its launch, insulin detemir will be available in 10mL vials as well as in the Levemir FlexPen. The FlexPen will require the use of NovoFine 30- or 31-gauge disposable needles. TH

Michele Kaufman is based in New York City.

References—Exubera

• Hollander PA, Blonde L, Rowe R, et al. Efficacy and safety of inhaled insulin (Exubera) compared with subcutaneous insulin therapy in patients with Type 2 diabetes: Results of a 6-month, randomized, comparative trial. Diabetes Care. 2004;27:2356-2362.
• Skyler JS, Weinstock RS, Raskin P, et al. The Inhaled Insulin Phase III Type 1 Diabetes Study Group. Use of inhaled insulin in a basal/bolus insulin regimen in Type 1 diabetic subjects: a 6-month, randomized, comparative trial. Diabetes Care. 2005 Jul:28(7):1630-1635.
• Rosenstock J, Zinman B, Murphy LJ, et al. Inhaled insulin improves glycemic control when substituted for or added to oral combination therapy in Type 2 Diabetes—a randomized, controlled trial. Ann Intern Med. 2005 Oct 18;143(8):549-588.
• The Pink Sheet, February 14, 2006; Volume 68, Number 7.Available at www.fda.gov/bbs/topics/news/2006/NEW01304.html. Last accessed March 8, 2006.

References—Levemir

• Levemir (insulin detemir [rDNA origin] injection) package insert. Novo Nordisk, Inc. Princeton, NJ; October 2005.
• Goldman JD, Lee KW. Insulin detemir—a new basal insulin analog. nn Pharmacother. 2005;39:502-507.
• Home P, Bartley P, Russell-Jones D, et al. Insulin detemir offers improved glycemic control compared with NPH insulin in people with Type 1 diabetes—a randomized clinical trial. Diabetes Care. 2004;27:1081-1087. Available at http://press.novonordisk-us.com/internal.aspx?rid=318. Last accessed March 1, 2006.