A	B	C	D	E	F	G	H	I	J	K	L	M	N	O	P	Q	R	S	T	U	V	W	X	Y	Z	AA	AB	AC	AD	AE	AF	AG	AH	AI	AJ	AK	AL	AM	AN	AO	AP	AQ	AR	AS	AT	AU	AV	AW	AX	AY	AZ	BA	BB	BC	BD	BE	BF	BG	BH	BI	BJ	BK	BL	BM	BN	BO	BP	BQ	BR	BS	BT
1	Main
2		Branded Name	Norvasc
3		Generic Name	Amlodipine besylate
4		Indication	Hypertension and Angina
5		Mechanism	Calcium Channel Blocker - dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker)
6			Inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Binds to both dihydropyridine and nondihydropyridine binding sites.
7			The contractile processes of cardiac muscle and vascular smooth muscle depend on the movement of extracellular calcium ions into these cells through specific ion channels.
8			Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells.
9		Administration	Oral
10		Competition	MYL/RDY's AmVaz, ACEs, ARBs, dieuretics, renins
11		PK	F=64-90%. Absorption produces peak plasma concentrations between 64-90%. 90% converted to inactive metabolites. 10% of parent and 60% of metabolites excreted through urine.
12			93% of the circulating drug is bound to plasma proteins in HTN patients. Terminal elimination half-life is 30-50 hours. Steady state reached after 7-8 days qd dosing.
13		Approved/Launched	7/31/1992
14		IP	COM 1/31/2007, Salt 9/25/2007. MYL has received final generic approval. Several firms have received tentative approvals including PRX, PRGO. Pediatric exclusivity?
15		Efficacy
16		Safety
17		Cost
18
19		Trying to switch people to Caduet
20
21		ASCOT
22		Stopped early due to greater than anticipated benefit for Norvasc vs. atenolol.
23		Published in Lancet 9/2005.
24
25		COM patent #4572909 expires 1/31/2007 (including P-extention)
26		Salt patent #4879303 expires 9/25/2007
27		DC of NJ dismissed PFE's lawsuit against RDY, clearing the way for non-AB, because PFE received a 3 year patent extention.
28		The judge felt the extention applied to the salt, not the compound itself. A higher court reversed the lower court decision.
29		Proceedings likely set for early 2006, final approval for MYL/RDY should be soon.
30		New patents have been filed. - Cowen
31
32			1994	1995	1996	1997	1998	1999	2000	2001	2002	2003	2004	2005	2006E	2007	2008	2009	2010	2011	2012	2013	2014	2015	2016	2017	2018	Notes	Q198	Q298	Q398	Q498	Q199	Q299	Q399	Q499	Q100	Q200	Q300	Q400	Q101	Q201	Q301	Q401	Q102	Q202	Q302	Q402	Q103	Q203	Q303	Q403	Q104	Q204	Q304	Q404	Q105	Q205	Q305	Q405	Q106	Q206	Q306	Q406E	Q107	Q207	Q307	Q407	Q108	Q208	Q308	Q408
33		Norvasc 9/07					2575	3030	3361	3581	3846	4335	4462	4612	5164	3356.6	335.66	134.264	26.852800000000002	5.370560000000001	1.0741120000000002	0.21482240000000005							567	618	671	719	694	713	778	807	782	805	847	928	860	879	881	962	931	886	963	1066	983	1003	1104	1245	1141	1032	1036	1253	1175	1156	1131	1244	1183	1158	1208
34		US									1775	1934	1991	2112															259	280	342	324	307	306	358	364	346	337	404	439	391	391	426	459	448	380	440	507	436	424	489	585	489	412	471	619	540	523	546	613	626	560	628
35		Ex-US									2071	2401	2471	2500															308	338	329	395	387	407	420	443	436	468	443	489	469	488	455	503	483	506	523	559	547	579	615	660	652	620	565	634	635	633	585	631	557	598	580