NEW DRUGS UPDATE Compiled by: Kumud Dahal, MD

1. DEFIBROTIDE: drug used in the treatment of veno-occlusive disease( now known as sinusoidal obstruction syndrome);this drug has shown promise in clinical trials. 2. RIFAXIMIN: new antibiotic with a very good safety profile that is used as alternative to neomycin and metronidazole for the treatment of hepatic encephalopathy. 3. Platelet lowering agents for the Tt of essential thrombocytosis: hydroxyurea, anagrelide or IFN-alfa 4. 5-AZACITIDINE( vidaza): drug approved for the Tt of Myelodysplastic syndrome; slows progression to AML and improves survival versus best supportive care; indicated for high risk MDS and for patients who are transfusion dependant; most common side effects: neutropenia, anemia and thrombocytopenia. 5. LENOLIDAMIDE: effective in patients with 5 q- syndrome variant of myelodysplastic syndrome. 6. SUNITINIB and SORAFANIB: these are two new agents approved for the treatment of metastatic renal cell cancer. Both appear more active and better tolerated than previously available agents. 7. ORAL TRETINOIN: used for the treatment of acute promyelocytic leukemia. Tt results in complete remission in >90% of patients. After consolidation chemotherapy, approx. 75% of patients are cured. 8. IMATINIB( GLEEVEC): orally administered medication designed to inhibit bcr-abl tyrosine kinase. Currently the first line therapy for CML. Even blast phase CML or Philadelphia chromosome positive acute leukemia may respond to this drug. Also for the Tt of Gastrointestinal Stromal tumors(GIST) 9. BORTEZOMIB: a proteasome inhibitor that degrades ubiquinated proteins, has recently been approved for the treatment of multiple myeloma that has progressed despite two previous treatments. ADR mainly thrombocytopenia and neuropathy. 10. FLUDARABINE: for the Tt of CLL. 11. CLADRIBINE: also called 2-chlorodeoxyadenosine. Is a purine substrate analog that is resistant to degradation by adenosine deaminase. For the Tt of hairy cell leukemia. 12. TEMOZOLOMIDE: an oral alkylating agent with activity in primary and metastatic brain tumors. 13. GEMCITABINE: nucleoside analog ( belongs to group of ANTIMETABOLITES). 14. MITOXANTRONE: is structurally similar to doxorubicin and daunorubicin , but is associated with less cardiac toxicity. Mucositis and myelosuppression are dose limiting; a bluish discoloration of urine and sclera may occur.

15. 2- DEOXYCOFORMYCIN: is isolated from streptomyces; acts as an inhibitor of adenosine deaminase. Myelosuppression is the chief toxicity. 16. L-ASPARAGINASE: hydrolyses asparagines, depleting cells of an essential substrate in protein synthesis. Allergic or anaphylaxis may occur. Other ADR include hemorrhagic pancreatitis, hepatic failure with depression of clotting factors and encephalopathy. 17. IRINOTECTAN: is a topoisomerase 1 inhibitor. Myelosuppression is dose limiting. It can produce severe diarrhea, which can be treated with atropine and loperamide. 18. AROMATASE INHIBITORS: third generation aromatase inhibitors have become available for Tt of postmenopausal women with hormone responsive breast cancer. They are ANASTROZOLE, LETROZOLE AND EXEMESTANE. Most common ADR are hot flashes and night sweats. 19. ALEMTUZUMAB: humanized antibody to CD 52(present on B and T cells); used for the Tt of CLL. 20. BEVACIZUMAB: targets VEGF and is approved for the Tt of colon cancer, and has activity in breast and lung cancer. Common ADR include hypertension and proteinuria. 21. CETUXIMAB and PANITUMUMAB: target EGFR; approved for the Tt of colon cancer. Toxicities include infusion reactions, rash and diarrhea. 22. GEMTUZUMAB: directed against CD33 and indicated in myeloid leukemia. 23. IBRITUMOMAB and IODINE 131 TOSITUMOMAB: are radiolabelled antibodies indicated for Tt of NHL. 24. ERLOTINIB: is a TKI targeting EGFR approved in NSCLC and with activity in pancreatic cancer as well. 25.GLUCAGON LIKE PEPTIDE 1 (GLP 1) AGONISTS: is an intestinal peptide that is secreted in response to food and regulates postprandial glycemia. It also protects and induces proliferation of beta cells, making it an attractive alternative therapy for diabetes. 26.EXENATIDE,a GLP-1 receptor agonist, has been shown to decrease postprandial hyperglycemia, reduce glucagon secretion and induce weight loss. It has been approved as an adjunctive therapy to sulfonylureas and /or metformin in patients who have not achieved control with these agents. 27.PEGVISOMANT: is a new growth hormone antagonist that lowers IGF-1 to normal in almost all patients. Approved for Tt of acromegaly. 28.FEBUXOSTAT:a new class of uric acid lowering drug, is a nonpurine selective inhibitor of xanthine oxidase; used for the Tt of gout. 29.URICASE: catabolizes uric acid to more soluble product, allantoin. It is used to treat tumor lysis syndrome. 30.FENOLDOPAM: is a selective agonist to peripheral dopamine-1 receptors, which produce vasodilation, increases renal perfusion, and enhance natriuresis. It has a short duration of action; the elimination half life is <10 minutes. It has an important application as parenteral therapy for high risk hypertensive surgical

patients and the perioperative management of patients undergoing organ transplantation. 31. EPLERENONE: is a selective aldosterone receptor antagonist without the hormonal side effect of spironolactone; is FDAapproved for Tt of HTN and HF and reduces mortality in patients with HF associated with acute MI. 32.RECOMBINANT BNP( NESIRITIDE): is an arterial and venous vasodilator; IV infusion reduces right atrial and left ventricular end diastolic pressures and SVR and results in increased cardiac output. It is approved for use in acute HF exacerbations and relieves HF symptoms early after administration. But it is not recommended for intermittent outpatient use. Most common ADR is hypotension. 33. COLESEVELAM: another bile acid binding resin. 34.EZETIMIBE: a cholesterol absorption inhibitor. It blocks cholesterol absorption at the level of enterocyte. It lowers LDLcholesterol. It can be used alone or in combination with statins. ADR include diarrhea, myalgias, and elevated liver enzymes. 35. IBUTILIDE: is the only drug approved by the US FDA for pharmacologic conversion of atrial fibrillation.. 36. MIDODRINE: an alfa1 adrenergic agonist that induces venous and arterial vasoconstriction, used for the treatment of patients with vasodepressor syncope. Main ADR is hypertension. 37. MELOXICAM: is a selective COX-2 inhibitor. 38. ESZOPICLONE: is a nonbenzodiazepine hypnotic just like ZOLPIDEM and ZALEPLON but offers a longer half life compared to these two agents. All should be used with caution in patients with impaired respiratory function. 39. FONDAPARINUX: is a selective inhibitor of factor Xa. Thus it doesnt prolong aPTT since it doesnt inhibit thrombin. It is not reversible with protamine. Clinical trials have proved the efficacy and safety profile of weight-based subcutaneously dosed fondaparinux for the Tt of VTE. 40. ARGATROBAN: is a synthetic direct thrombin inhibitor used for HIT therapy; reversal agent is not available. It increases aPTT and PT as well. 41. BOSENTAN -vasodilator/vasomodulator agent -for Tt of Pulmonary hypertension -effects: improves exercise capacity and delays time to clinical worsening. -ADR: hepatotoxicity 42. RECOMBINANT HUMAN DEOXYRIBONUCLEASE(Dnase, dornase-alpha, pulmozyme) -decreases viscoelasticity of sputum -improves pulmonary function and decreases the incidence of respiratory tract infection that requires parenteral antibiotics. -used in treatment for cystic fibrosis. 43.VARENICLINE: -binds to nicotine receptors, blocks their activation by nicotine, and prevents smoking induced reinforcement and reward.

- used smoking cessation. 44.ANTI IgE THERAPY: OMALIZUMAB -monoclonal antibody against IgE - used in the management of moderate and severe persistent asthma. 45. ACETYL CYSTEINE: -given 1 day before the procedure, it reduces the incidence and severity of radiocontrast nephropathy. 46. RASBURICASE: given prophylactically if the patient is at high risk for tumor lysis syndrome or after hyperuricemia develops despite prophylaxis. 47.TIGECYCLINE: is the only US FDA approved antibiotic in the class of GLYCYLCYCLINES. Its MOA similar to that of tetracyclines. The addition of glycyl side chains expands its activity against bacterial pathogens that are normally resistant to tetra- and minocycline. It has a broad spectrum of activity against Gm +ve, Gmve and anerobic bacteria except P.aeruginosa and proteus species. It is currently approved for the Tt of complicated skin and skin structure infections and complicated intraabdominal infections. It should be reserved for the treatment of tissue infections due to resistant pathogens such as VRE, Acinetobacter spp., and Enterobacter spp. 48.T-20 (ENFUVIRTIDE; HIV entry inhibitors): is a new class of ART that targets different stages of HIV entry process. It is a fusion inhibitor only available for subcutaneous use. 49. NITAZOXANIDE: for the treatment of cryptosporidium. 50. ALEMTUZUMAB: is a monoclonal antibody against the CD52, a molecule present on B and T cells. Subsequent antibody mediated cell lysis occurs, causing lymphocyte depletion. It has been used extensively for B cell CLL and has been utilized off label in transplantation as induction therapy. 51. OKT3: is a murine monoclonal antibody directed against the CD3 E chain associated with T cell receptor. OKT3 depletes CD3+ T cells and modulates CD3 expression. Most common ADR is cytokine release syndrome. 52.APREPITANT:Neurokinin-1 receptor antagonist ; currently indicated only for chemotherapy induced nausea and vomiting. 53. TEGASEROD: a 5 HT-4 agonist with prokinetic properties, used in gastroparesis. 54. To treat Hepatitis B: intereron alfa, lamivudine, adefovir, entecavir, telbivudine 55..PENTOXIFYLLINE: is a nonselective phosphodiestrase inhibitor with anti inflammatory activity and excellent safety profile that has shown improved survival in patients with severe alcoholic hepatitis( DF more than 32.) 56.TRIENTINE: to treat Wilsons disease. Similar side effects as penicillamine but with lower frequency. 57. TETRATHIOMOLYBDATE: with zinc therapy is the treatment of choice for patients of Wilsons disease presenting with neurological symptoms. 58.TERIPARATIDE: MOA: recombinant DNA PTH analog Use: to stimulate osteoblast and new bone formation

Continuous infusion would stimulate osteoclast activity Used for less than 2 years, may increase the risk for osteosarcoma. 59.BIVALIRUDIN: Thrombin specific anticoagulant Used with aspirin in unstable angina when undergoing PTCA. 60.ATOMOXETINE: Selective NE reuptake inhibitor Side effects: similar to those of TCAs 61. ECULIZUMAB: an antibody that inhibits the activation of terminal complement components, reduces hemolysis, hemoglobinuria, and the need for transfusion, and improves quality of life in paroxysmal nocturnal hemoglobinuria (PNH).