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.

Top Ten Health Stories of the Year 2010

The year 2010 saw a lot of ‘hustle and bustle’ in the medical circle. Here are the Top 10 stories as viewed by eMedinewS.

1. Overhauling of Medical Council of India: The major story of the year was the arrest of MCI President Dr. Ketan Desai, dissolution of the MCI; appointment of six out of seven Board of Governors; subsequent release of Dr. Ketan Desai on bail, common entrance exam for MBBS; reduction in forensic faculty requirement; increase in retirement age to seventy and the suspense behind 7th seat of Board of Governors etc.
2. Medical Council of India action against Indian Medical Association: MCI took action against the IMA President and Secretary for violation of MCI Ethics on the ground that IMA should not have endorsed Pepsi products. The IMA had to approach High Court to take a stay. The matter is now in the High Court. Is that a start of MCI actions against ethics violations? Will it act against the cut system?
3. Delhi Bug: A huge controversy arose when British Medical Journal broke a story about NDM1 bug being named after New Delhi. The medical circle in India said that it was unfair and was an attempt to sabotage the medical tourism in India. The new bug is a gram negative bacteria showing resistance to all present antibiotics. New Delhi metallo–beta–lactamase (NDM–1) is an enzyme that makes bacteria resistant to a broad range of beta–lactam antibiotics. These include the antibiotics of the carbapenem family, which are a mainstay for the treatment of antibiotic–resistant bacterial infections. The gene for NDM–1 is one member of a large gene family that encodes beta–lactamase enzymes called carbapenemases. Bacteria that produce carbapenemases are often referred to in the news media as “superbugs” because infections caused by them are difficult to treat. Such bacteria are usually only susceptible to polymyxins and tigecycline. NDM–1 was first detected in a Klebsiella pneumoniae isolate from a Swedish patient of Indian origin in 2008. It was later detected in bacteria in India, Pakistan, the United Kingdom, the United States, Canada, Japan and Brazil. The most common bacteria that make this enzyme are Gram negative such as Escherichia coli and K. pneumoniae, but the gene for NDM–1 can spread from one strain of bacteria to another by horizontal gene transfer.
4. H1N1 havoc: H1N1 created great havoc, but ultimately, proved to be a ‘much hyped’ virus with mortality even lower than the regular human flu virus. Most of the hospitals who had started special H1N1 virus wards, now do not have these wards.
5. Chikungunya epidemic: The latest epidemic in the North India was that of Chikungunya with patients presenting with fever, rash and joint pains. It complicated the pre–existing dengue epidemic in the society.
6. Dengue with a difference: This year dengue was different than other years, came with more GI symptoms, pancreas involvement, dengue hepatopathy and lot of skin reactions. The platelet count dropped to less than 10000 but most required no platelet transfusion.
7. Diabetes diagnosis: The year saw a new advancement where A1C is to be used for diagnosis of diabetes and not fasting sugar. An A1C >6.5% means diabetes.
8. New pill for HIV prevention: A new pill is now available for HIV prevention along with condoms. It is to be used before the act and continues for seven days. In a trial involving nearly 2,500 HIV–negative, but high risk, gay men in six countries, researchers found that a combination antiretroviral pill (tenofovir and emtricitabine) reduced the risk of HIV infection by 44%, compared with placebo. When scientists looked more carefully at the study volunteers who took the medication most faithfully, on a daily basis, they found that the risk of contracting HIV was even lower — 73% lower than the placebo group. More studies will need to confirm the benefit of antiretrovirals in the prevention of HIV, and public health experts warn that even if the results hold up, it would not replace the best method of prophylaxis: safe sex and consistent use of condoms. That’s because the way so–called pre–exposure prophylaxis, or PrEP, works is to load up high–risk people with HIV–disabling antiretroviral drugs before exposure to the virus, which allows the medication to hit HIV as early as possible. But the drugs do not work as a vaccine would, by priming the immune system to actually prevent infection.
9. National Programme for Prevention & Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS) started in the country:At last, Govt. of India, Ministry of Health and Family Welfare has started the above program.
10. New drug for premature ejaculation: The year ended with the launch of an SOS drug for premature ejaculation. This will be breakthrough for the community. Premature ejaculation, the most common sexual problem apart from erectile dysfunction, has been often found to put marriages under strain. While the existing drugs, which are not specific to treat premature ejaculation, need to be taken regularly, the new pill can be popped just a few hours before intercourse. It works by altering levels of serotonin, a chemical in the brain. The drug, dapoxetine, comes from a family of drugs called selective serotonin reuptake inhibitors, which block the reabsorption of the neurotransmitter serotonin.

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)

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Newer drugs for Epilepsy

Lacosamide

Lacosamide is an amino acid-related compound that has been studied in both pain syndromes and partial seizures.

Mechanism of Action: Lacosamide enhances slow inactivation of voltage-gated Na+ channels. It also binds to the collapsin-response mediator protein, CRMP-2, thereby blocking the effect of neurotrophic factors such as BDNF and NT3 on axonal and dendritic growth.

Rufinamide

Rufinamide is a new triazole derivative with little similarity to other antiseizure drugs. It is approved for use in Lennox-Gastaut syndrome and preliminary evidence suggests that it may also be useful in other difficult-to-treat epilepsy syndromes.

Single daily poly-pill for HIV

In a prospective, randomized trial, a single daily tablet containing efavirenz, emtricitabine, and tenofovir (Atripla; Bristol Myers Squibb & Gilead Sciences LLC) maintained viral suppression in HIV-1 infected patients as well as the standard multiple-pill regimen.

The report of the study, published in the Journal of the Acquired Immune Deficiency Syndrome, notes that at baseline, all 300 participants were on stable antiretroviral therapy (ART) regimens, with viral loads of less than 200 copies/mL for at least 3 months. Their mean CD4 count was 540 cells/�L, and 96% of subjects had HIV-1 RNA <50>

On randomization, 203 were assigned to the Atripla regimen while 97 remained on their baseline regimen. The entire 48-week study was completed by 266 patients.

In the intent-to-treat analysis, it was found that at 48 weeks, the primary endpoint -- HIV-1 RNA below 200 copies/mL -- had been achieved by 89% of the patients in the single-tablet group versus 88% of those on unmodified antiretroviral regimens, "indicating noninferiority" of the newer approach.

Similarly, there was no significant difference between groups in maintenance of viral load below 50 copies/mL and no significant changes in CD4 cell counts within or between the two arms of the study.

Discontinuation rates were similar between the groups, but more patients in the single-tablet group discontinued due to adverse events, "most commonly for nervous system symptoms," according to the investigators.

Three patients in the single-tablet group and one in the control group had virologic failure.

"In summary," the researchers conclude, "patients who were stable and virologically suppressed while receiving a wide array of non-nucleoside reverse transcriptase inhibitor- and protease inhibitor-based antiretroviral regimens and had their treatment simplified to a single-tablet regimen of efavirenz, emtricitabine, and tenofovir maintained high rates of virologic suppression compared to those who continued their regimen unmodified."

Source: J Acquir Immune Defic Syndr 2009;51:163-174.

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.