Drugs Update

New drugs approved for marketing in India during November-December 2011

Source: http://cdsco.nic.in

Diazinon Flea Drops Spot on Dogs 30.0% w/w	For dogs infected with fleas.
Cabazitaxel Injection 60mg / 1.5ml	In combination with prednisone for treatment of patients with hormone-refractory metastatic prostrate cancer previously treated with a docetaxel-containing treatment regimen.
Trifluridine Eye Drops 1% w/v	For the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex viruses type 1 and 2.
Fosaprepitant (as Dimeglumine) for Injection 150mg.	1. Prevention of acute and delayed nausea and vomiting associated with highly emetogenic cisplatin based cancer chemotherapy in adults. 2. Prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy in adults.
Abiraterone Acetate Tablets 250mg	In combination with prednisone for the treatment of patients with metastatic castration-resistant prostrate cancer who have received prior chemotherapy containing docetaxel.
Dabigatran Etexilate( as Mesilate) hard gelatin Capsules 75mg/110mg/150mg	For prevention of stroke, systemic embolism and reduction of vascular mortality in adult patients with atrial fibrillation.
Crizotinib  hard gelatin Capsules 200mg/250mg	For the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) – positive as detected by an FDA-approved test.

Drugs  banned in India in 2011

Source: http://cdsco.nic.in

1.      Gatifloxacin

2.      Tegaserod

3.      Nimesulide for children below 12 years.

4.      Cisapride

5.      Phenyl propanolamine

6.      Human placental extract

7.      Sibutramine

8.      R-Sibutramine

FDA approvals in January 2012

Source: http://drugs.com

1.      Fentanyl Sublingual Spray

Opioid analgesic sublingual spray formulation indicated for the treatment of breakthrough cancer pain.

2.      Glucarpidase Injection

Carboxypeptidase enzyme indicated for the treatment of toxic plasma methotrexate levels in patients with delayed methotrexate clearance due to impaired renal function.

3.      Ciclesonide Nasal Aerosol

Corticosteroid nasal spray indicated for the treatment of symptoms associated with seasonal and perennial allergic rhinitis.

4.      Ingenol mebutate Topical Gel

Inducer of cell death indicated for the topical treatment of actinic keratosis.

5.      Axitinib Tablets        

Kinase inhibitor indicated for the treatment of advanced renal cell carcinoma

6.      Exenatide Extended-Release Injectable Suspension

Glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.

7.      Vismodegib Capsules

Hedgehog pathway inhibitor for the treatment of patients with advanced basal cell carcinoma (BCC).

8.      Ivacaftor Tablets

Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator indicated for the treatment of cystic fibrosis (CF) in patients age 6 years and older who have a G551D mutation in the CFTR gene.

New molecular entities (NMEs) approved in 2010

• Asenapine (Saphris, Merck & Co., Inc.)
• Bepotastine (Bepreve, ISTA Pharmaceuticals)
• Dronedarone (Multaq, Sanofi-aventis)
• Liraglutide (Victoza, Novo Nordisk)
• Tocilizumab (Actemra, Genentech)
• Ustekinumab (Stelara, Centocor Ortho Biotech)
• For details see http://www.medscape.com/viewarticle/731720

• New Drug Review 2010

  Jack DeRuiter, PhD; Pamela L. Holston, RPh, BS, BA
  Posted: 11/10/2010; US Pharmacist © 2010 Jobson Publishing

Onabotulinumtoxin A for Migraine

The US Food and Drug Administration (FDA) has approved onabotulinumtoxinA (Botox; Allergan Inc) for headache prophylaxis in patients with adult chronic migraine who suffer headaches on 15 or more days per month, each lasting more than 4 hours.

    To treat chronic migraine, onabotulinumtoxinA is given approximately every 12 weeks as multiple injections around the head and neck. The recommended dose is 155 units (1 mL) divided across 7 head and neck muscles, administered at intervals of at least 12 weeks.

The most common adverse reactions reported by patients being treated with onabotulinumtoxinA for chronic migraine were neck pain (9%) and headache (5%).

Marketed as Botox and Botox Cosmetic, onabotulinumtoxinA has a boxed warning that the effects of the botulinum toxin may spread from the area of injection to other areas of the body, causing symptoms similar to those of botulism.Symptoms include swallowing and breathing difficulties that can be life-threatening.

 Source: FDA New Drug Web site (www.fda.gov)

New screening method for Anticancer drugs

Many researchers believe tumour growth is driven by cancerous stem cells that, for reasons not yet understood, are highly resistant to standard treatments. Chemotherapeutic agents may kill off 99 percent of the cells in a tumor, but the stem cells that remain can make the cancer recur or spread to other tissues in the body to cause new cancers.

Stem cells, unlike mature cells, can constantly renew themselves and are thought to be the source of cancers when, through mutations in their DNA, they throw off their natural restraints.
a team at the Broad Institute devised a way of screening for drugs that attack cancer stem cells but leave ordinary cells unharmed.

Cancer stem cells are hard to maintain in sufficient numbers, but the Broad Institute team devised a genetic manipulation to keep breast cancer stem cells trapped in the stem cell state.

The team, led by Piyush B. Gupta, screened some 16,000 chemicals, including all known chemotherapeutic agents approved by the FDA. The team reported in the Cell that 32 of the chemicals selectively went after cancer stem cells. The screening system proves for the first time that it is possible to single out cancer stem cells with drugs that leave ordinary cells alone. Only one of the 32 chemicals is approved as a drug for cancer.

Another approach to concentrating on cancer stem cells, based on the use of antibodies, was reported this month by OncoMed Pharmaceuticals.

The cancer stem cell theory has been thrust into the spotlight in the last five years with the discovery of stem cells in many types of solid tumors, including those of the breast, brain, prostate, colon, bladder and pancreas.

Source: http://www.nytimes.com/2009/08/14/health/research/14cancer.html?_r=1&8au&emc=au

'Good Clinical Practices' HelpDesk

The GCP HelpDesk is a support service provided to respond to queries raised by Investigators/Physicians on Good Clinical Practice in Clinical Research. It provides a central point of contact on global GCP issues and ensures that consistent replies are provided to questions. The HelpDesk also allows the users to give their feedback, which will be continuously reviewed in order to improve its services and helps in regularly updating the list of Frequently Asked Questions (FAQs) published on its website. In this website you will find Good Clinical Practice (GCP) related information for the Clinical Research Industry professionals on request.

The GCP HelpDesk is designed to provide information for clinical research professionals with questions regarding handling, conducting and managing clinical research as per GCP, FDA and other Regulations. This HelpDesk is aimed to provide transparency from resources and expertise in the field of Clinical Research with the recent developments and changes in the guidelines for clinical research professionals.The GCP HelpDesk is a searchable website that will match the question with solution by industry experts and other dedicated sites to a specific area. Both simple and complicated questions are welcomed.

To create an account and start using the services go to: http://www.gcphelpdesk.com/index.php/component/user/?task=register

Some new drug approvals in June 2009

Simponi
Pharmacological class: TNF blocker.
Active Ingredient: Golimumab 50mg/0.5mL; soln for SC inj; preservative-free.
Indication: Moderately to severely active rheumatoid arthritis (RA), in combination with methotrexate (MTX). Active psoriatic arthritis (PsA), alone or with MTX. Active ankylosing spondylitis (AS).
Company: Centocor Ortho Biotech, Inc.

Axert approved for migraine treatment in adolescents

The FDA has approved Axert (almotriptan malate tablets, from Ortho-McNeil Janssen), a selective 5-HT1B/1D receptor agonist, for the acute treatment of migraine headache in adolescents 12-17 years of age with a history of migraine attacks lasting ≥4 hours.

Reclast approved for biennial dosing regimen to prevent female osteoporosis

The FDA has approved Reclast (zoledronic acid, from Novartis) injection for the prevention of osteoporosis in women for two years with a single dose.

Lamictal XR approved for treatment of epilepsy

GlaxoSmithKline announced that the FDA has approved Lamictal XR (lamotrigine extended-release tablets) as a once-a-day add-on therapy for epilepsy patients ≥13 years of age with partial onset seizures.

Nuvigil launched for excessive sleepiness

Nuvigil (armodafinil tablets) is now available from Cephalon in 50mg, 150mg, and 250mg dosage strengths.

Vyvanse approved for pediatric ADHD control 13 hours post-dose

Shire Pharmaceuticals has received FDA approval for a labeling change for its once-daily Attention Deficit Hyperactivity Disorder (ADHD) treatment Vyvanse (lisdexamfetamine dimesylate capsules).

Cycloset -a new antidiabetic

The U.S. FDA approved Cycloset, a new quick-release oral formulation of bromocriptine mesylateis, which is the first therapy directly targeting the body’s dopamine activity to improve glycemic control. It is also the only drug to be approved subsequent to the FDA's guidelines that require studies demonstrating that diabetes drugs do not increase cardiovascular risk.

Preclinical studies indicate that while an increase in dopamine activity leads to improvements in diabetes, the time of day of the increased dopamine activity is also important. Studies in diabetic animals have shown that increased dopaminergic activity at a particular time of day is most effective in “resetting” the biological clock neurochemistry to a physiology that improves diabetic dysmetabolism. Taken orally, once-a-day, in the morning, Cycloset provides a single brief pulse of dopamine agonist activity shortly after its administration. Morning Cycloset improves post-prandial (after-meal) glucose without increasing plasma insulin concentrations, and the beneficial effects of Cycloset on post-meal glycemic control in patients with Type 2 diabetes are demonstrable many hours after the drug has been substantially cleared from the circulation, for example at lunch and dinner.

Mechanism: Bromocriptine mesylate, an ergot derivative, is a sympatholytic dopamine D2 agonist that exerts inhibitory effects on serotonin turnover in the central nervous system. It has been proposed that bromocriptine can reverse many of the metabolic alterations associated with obesity by resetting central (hypothalamic) circadian organization of monoamine neuronal activitties. Indeed, bromocriptine, if administered systemically or into the cerebral ventricle during the early hours of the light cycle, prevents or reverses seasonal fattening, insulin resistance, and decreased endogenous (hepatic) glucose production in mammals. Moreover, timed bromocriptine treatment decreased body weight and improved glucose tolerance in obese individuals who were instructed to follow a hypocaloric diet . Bromocriptine has also been shown to reduce mean daylong plasma glucose, triglyceride, and free fatty acid (FFA) levels in the absence of a change in body weight in obese nondiabetic women.

New Pharmacological Drug Classes Introduced in 2008

Pharmacologic Class	First to be Marketed in the U.S.	FDA Approved Indication	11th Edition Reference
C1 inhibitor	C1 inhibitor (Cinryze)	Routine prophylaxis against angioedema attacks in patients with hereditary angioedema	page 1405
CXCR4 chemokine receptor inhibitor	plerixa (Mozobil)	Mobilization of granulocyte-colony stimulating factor induced hematopoietic stem cells to the peripheral blood prior to collection	page 1274
peripherally acting µ-opioid receptor antagonist	alvimopan (Entereg)	Acceleration of the time to gastrointestinal recovery following bowel surgery	pages 561-562
	methylnaltrexone (Relistor)	Treatment of opioid-induced constipation
thrombopoietin receptor agonist	eltrombopag (Promacta)	Treatment of thrombocytopenia in patients with chronic immune thrombocytopenic purpura	pages 1441-1442
	romiplostim (Nplate)

Drugs Licensed in 2008 With Mechanisms Similar to Previously Approved Drugs

Generic Name	Brand Name	Pharmacology	2008 FDA Approved Indication	Pharmacologically Similar Agents	11th Edition Reference
bendamustine	Treanda	alkylating agent	Treatment of chronic lymphocytic leukemia	busulfan, carmustine, chlorambucil, cyclophosphamide, ifosfamide, melphalan	pages 1322-1327
certolizumab	Cimzia	tumor necrosis factor inhibitor	Management of Chron's disease	infliximab	page 1419
clevidipine	Cleviprex	dihydropyridine calcium channel antagonist	Treatment of hypertension	amlodipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine nisoldipine	pages 832-838, 857-858
degarelix	none	GnRH receptor antagonist	Treatment of prostate cancer	goserelin, histrelin, leuprolide, triptorelin	pages 1387-1388
desvenlafaxine (major metabolite of venlafaxine)	Pristiq	selective serotonin and norepinephrine reuptake inhibitor	Treatment of major depressive disorder	venlafaxine	pages 434t, 437t, 439t, 444t,
difluprednate	Durezol	opthalmic corticosteroid	Treatment of ocular inflammation	prednisolone	pages 1724-1725
ethinyl estradiol/levonorgestrel	LoSeasonique	oral contraceptive	Prevention of pregnancy	ethinyl estradiol/levonorgestrel (Seasonique)	pages 1563-1567
etravirine	Intelence	non-nucleoside reverse transcriptase inhibitor	Treatment of HIV-1 infection	delavridine, efavirenz, nevirapine	pages 1292-1297
fesoterodine	Toviaz	muscarinic receptor antagonist	Treatment of overactive bladder	darifenacin, solifenacin, tolterodine	pages 173-174
fosaprepitant (produrg of aprepitant)	Emend	substance P/neurokinin 1 receptor antagonist	Prevention of nausea and vomiting associated with emetogenic cancer chemotherapy	aprepitant	pages 1005
fospropofol (produrg of propofol)	Lusedra	sedative-hypnotic	Monitored anesthesia care sedation	propofol	pages 350-351
gadofosveset	Vasovist	gadolinium-based contrast agent	Magnetic resonance imaging	gadodiamide, gadoteridol
gadoxetate	Requip XL
regadenoson	Lexiscan	adenosine receptor agonist	Pharmacologic stress agent for radionuclide myocardial perfusion imaging	adenosine	page 917
rilonacept (also known as IL-1 Trap)	Arcalyst	interleukin-1 blocker	Treatment of cryopyrin-associated periodic syndromes, including Familial Cold Autoinflammatory Syndrome and Muckle-Wells Syndrome	anakinra	page 672
silodosin	Rapaflo	alpha-1 adrenergic receptor antagonist	Treatment of benign prostatic hyperplasia	prazosin, terazosin, doxazosin, tamsulosin, alfuzosin	pages 269-271
tapentadol	none	m-opioid receptor agonist & norepinephrine reuptake inhibittor	Relief of pain	tramadol	page 566
tetrabenazine	Xenazine	monoamine depletor	Treatment of chorea associated with Huntington´s disease	reserpine	pages 173, 541

New molecular entities approved by the US FDA's Center for Drug Evaluation and Research in 2008

FROM THE FOLLOWING ARTICLE:

2008 FDA drug approvals

Bethan Hughes

Nature Reviews Drug Discovery 8, 93-96 (February 2009)

doi:10.1038/nrd2813

Generic name (Trade name)	Company*	Indication(URL of label information if available)	Properties	Date
Etravirine (Intelence)	Tibotec	HIV-1(http://www.fda.gov/cder/foi/label/2008/022187lbl.pdf)	Non-nucleoside reverse transcriptase inhibitor	18 Jan (P)
Desvenlafaxine (Pristiq)	Wyeth	Major depressive disorder(http://www.fda.gov/cder/foi/label/2008/021992lbl.pdf)	Selective serotonin and noradrenaline reuptake inhibitor	29 Feb (S)
Bendamustine hydrochloride (Treanda)	Cephalon	Chronic lymphocytic leukaemia(http://www.fda.gov/cder/foi/label/2008/022249lbl.pdf)	Mechlorethamine derivative with DNA-alkylating activity	20 Mar (P, O)
Regadenoson (Lexiscan)	CV Therapeutics	Pharmacological stress agent for radionuclide imaging (http://www.fda.gov/cder/foi/label/2008/022161lbl.pdf)	A2A adenosine receptor agonist	10 Apr (S)
Methylnaltrexone bromide (Relistor)	Progenics	Opioid-induced constipation	Peripherally acting  opioid receptor antagonist	24 Apr (S)
Alvimopan (Entereg)	Adolor	To accelerate gastrointestinal recovery following bowel resection surgery(http://www.fda.gov/cder/foi/label/2008/021775lbl.pdf)	Peripherally acting  opioid receptor antagonist	20 May (S)
Difluprednate (Durezol)	Sirion	Inflammation and pain associated with ocular surgery (http://www.fda.gov/cder/foi/label/2008/022212lbl.pdf)	Ocular corticosteroid thought to act by the induction of phospholipase A2 inhibitory proteins	23 Jun (P)
Gadoxetate disodium (Eovist)	Bayer	Gadolinium-based contrast agent(http://www.fda.gov/cder/foi/label/2008/022090lbl.pdf)	Paramagnetic compound	3 Jul (S)
Clevidipine butyrate (Cleviprex)	The Medicines Company	Peri-operative hypertension when oral therapy is not feasible or not desirable	Short-acting dihydropyridine calcium channel antagonist	1 Aug (S)
Tetrabenazine (Xenazine)	Prestwick	Chorea associated with Huntington's disease(http://www.fda.gov/cder/foi/label/2008/021894lbl.pdf)	Monoamine-depleting agent	15 Aug (P, O)
Iobenguane I-123 (AdreView)	GE Healthcare	Radiopharmaceutical agent for the detection of primary or metastatic phaeochromocytoma or neuroblastoma (http://www.fda.gov/cder/foi/label/2008/22290lbl.pdf)	Taken up by the noradrenaline transporter in adrenergic nerve terminals	19 Sep (P, O)
Silodosin (Rapaflo)	Watson	Benign prostatic hyperplasia(http://www.fda.gov/cder/foi/label/2008/022206lbl.pdf)	1 adrenoceptor antagonist	8 Oct (S)
Lacosamide (Vimpat)	Schwarz	Partial-onset seizures in epilepsy (http://www.fda.gov/cder/foi/label/2008/022253lbl.pdf)	Selectively enhances slow inactivation of voltage-gated sodium channels and binds to collapsin response mediator protein 2	28 Oct (S)
Fesoterodine fumarate (Toviaz)	Pfizer	Overactive bladder disorder(http://www.fda.gov/cder/foi/label/2008/022030lbl.pdf)	Competitive muscarinic receptor antagonist	31 Oct (S)
Rufinamide (Banzel)	Eisai	Seizures associated with Lennox–Gastaut syndrome (http://www.fda.gov/cder/foi/label/2008/021911lbl.pdf)	Sodium channel activity modulator	14 Nov (S)
Eltrombopag (Promacta)	GlaxoSmithKline	Thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (http://www.fda.gov/cder/foi/label/2008/022291lbl.pdf)	Thrombopoietin receptor agonist	20 Nov (P, O)
Tapentadol hydrochloride‡	Ortho–McNeil–Janssen	Moderate to severe acute pain	opioid receptor agonist and noradrenaline reuptake inhibitor	20 Nov (S)
Fospropofol disodium (Lusedra)	Eisai	Monitored anaesthesia care sedation (http://www.fda.gov/cder/foi/label/2008/022244lbl.pdf)	Prodrug of propofol	12 Dec (S)
Plerixafor (Mozobil)	Genzyme	Autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma (http://www.fda.gov/cder/foi/label/2008/022311lbl.pdf)	CXCR4 antagonist	15 Dec (P, O)
Gadofosveset (Vasovist)	Epix	Gadolinium-based contrast agent	Paramagnetic compound	22 Dec (S)
Degarelix (Firmagon)	Ferring	Advanced prostate cancer (http://www.fda.gov/cder/foi/label/2008/022201lbl.pdf)	Gonadotropin-releasing hormone receptor antagonist	24 Dec (S)
*The company that submitted the original new drug application to the US FDA.‡Trade name not available at the time of going to press. O, FDA orphan designation; P, FDA priority review; S, FDA standard review.