EXHIBIT 10.46
                                                                   -------------

                                 AMENDMENT THREE
                         TO THE MANUFACTURING AGREEMENT
                        BY AND BETWEEN VIVUS AND CHINOIN

     This Amendment Three ("Amendment Three"), effective as of November 21, 2002
("Amendment Date"), by and between VIVUS, Inc., having a principal place of
business at Mountain View, CA United States of America ("VIVUS"), and CHINOIN
Pharmaceutical and Chemical Works, Ltd., having a principal place of business at
H-1045, Budapest, To u. 1-5 Hungary ("CHINOIN") (VIVUS and CHINOIN collectively,
the "Parties"), amends (i) that certain Manufacturing Agreement by and between
the Parties dated December 20, 1995 (the "Agreement") and (ii) Amendment One to
the Agreement dated December 11, 1997 ("Amendment One") and (iii) Amendment Two
to the Agreement dated December 18, 1998 ("Amendment Two")

     The Parties desire to amend the Agreement, the Amendment One and Amendment
Two as set forth herein below;

     NOW, THEREFORE, the Parties agree as follows:

1.   AMENDMENT. This Amendment Three hereby amends the Agreement to incorporate
the terms and conditions set forth in this Amendment Three. The relationship of
the Parties shall continue to be governed by the terms and conditions of the
Agreement, the Amendments One and Two, as amended herein; and in the event that
there is any conflict between the terms and conditions of the Agreement or
Amendment One or Two and this Amendment Three, the terms and conditions of this
Amendment Three shall control. As used in this Amendment Three, all capitalized
terms shall have the meanings defined for such terms in this Amendment Three or,
if not defined in this Amendment Three, the meanings defined in the Agreement.

2.   MODIFICATION TO THE AGREEMENT.

     2.1 The Parties hereby acknowledge the change of the principal place of
business of VIVUS from 605 East Fairchild Drive, Mountain View, CA 94043, to
1172 Castro Street, Mountain View, CA 94040.

     2.2 The Parties hereby confirm that in the frame of the Agreement VIVUS has
firmly ordered from CHINOIN under PO# [*] the supply of [*] Product for the year
1998. After CHINOIN having delivered [*], VIVUS has requested CHINOIN to stop
manufacturing and to postpone all further shipments. According to Amendment Two
and further discussion of the Parties, [*] of Product was delivered in 1999 and
2000 to VIVUS. A further [*] of Product ordered for 1998 and the [*] minimum
purchasing obligation of VIVUS for the calendar year of 1999, for a total of
[*], the only obligation of VIVUS until December 31, 2002 according to Amendment
Two, has not been ordered by VIVUS and has not been manufactured by CHINOIN.

     2.3 The Parties hereby agree to prolong the validity of the Agreement for
calendar years 2003 to 2008, being considered as seventh, eighth, ninth, tenth,
eleventh and twelfth Agreement Years, respectively.
<PAGE>

     2.4 CHINOIN agrees to update its manufacturing process to meet the EAEMP
Recommendation July 1999 on the compliance with the CPMP guideline on residual
solvents.

     2.4.1.    Chinoin will manufacture [*] of Product, approximately [*] each,
               in a campaign starting in 2002. The [*] will be completed no
               later than January 31, 2003. The [*] and [*]  [*]  will follow
               thereafter and will be completed no later than February 28, 2003.
               During this campaign, CHINOIN will apply a change of
               manufacturing process characterized with the replacement of [*]
               to a more desirable [*] in manufacturing step 9 of the Product as
               numbered in CHINOIN's DMF and other changes deemed necessary by
               CHINOIN in connection with such change.

     2.4.2.    CHINOIN agrees to carry out all tests and studies necessary to
               prove the equivalence of Product manufactured with the modified
               process using these [*], including stability studies, and submit
               the description of the changes and all related results as
               required by the regulatory authorities in a schedule set forth
               below:

               a.        To the US FDA with three (3) month stability results no
                         later than May 31, 2003;

               b.        To the European and other regulatory authorities no
                         later than thirty (30) days after receipt of a written
                         request from VIVUS, such written request to occur no
                         earlier than May 31, 2003, such submission to include
                         the latest stability results available at the time of
                         submission.

     2.4.3.    CHINOIN agrees to provide VIVUS with a detailed analytical report
               on its findings on these batches of Product at the time of their
               qualification and results of its stability studies at the time
               such results are available.

     2.4.4.    CHINOIN agrees to carry out similar necessary tests and studies
               including stability study on at least its [*] of the Product
               manufactured in [*] size with its modified process following the
               [*] in [*] size as described above. Testing results on such
               additional [*] will be submitted to the regulatory authorities in
               the customary manner with due advance consultation with VIVUS.

     2.5 CHINOIN agrees to amend its current Specification:

               a)        To meet the EAEMP Recommendation July 1999 on the
                         compliance with the CPMP guideline on residual
                         solvents;

               b)        To meet the requirements of USP 25 Suppl.1 (April 1,
                         2002);

               c)        To meet the requirements of the European Pharmacopeia,
                         2001:1448 FOR ALPROSTADIL;

               d)        To meet additional VIVUS requirements.

     2.5.1.    These future requirements are set forth in Exhibit A to this
               Amendment Three.

     2.5.2.    CHINOIN agrees to submit its updated Specification as a part of
               its regulatory submissions set forth in Section 2.4.2 of this
               Amendment Three.
<PAGE>

     2.5.3.    The updated Specification shall be applicable for the first time
               to batches manufactured by CHINOIN with the modified process set
               forth in Section 2.4.1 of this Amendment Three.

     2.6 VIVUS agrees to carry out all tests and studies necessary to acquire
the approval of the US, EU and other regulatory authorities for its use of
Product manufactured with the modified process of CHINOIN as active ingredient
in its finished product MUSE.

     2.6.1.    VIVUS agrees that these tests and studies shall include
               manufacture and stability studies of validation batches of MUSE
               using each of the [*] of Product received from CHINOIN as the
               first shipment in 2003 as set forth in Section 2.7.1 below.

     2.6.2.    VIVUS agrees to submit a supplement to its NDA for approval by
               the US FDA no later than July 31, 2003 or as soon as such studies
               are completed.

     2.6.3.    VIVUS agrees to provide to its European Union licensed
               distributor, as expeditiously as possible, any and all
               assistance, information and/or materials in VIVUS possession to
               submit a Type I Variation to its European Product License upon
               completion of studies necessary for such submission to the
               European regulatory authorities.

     2.6.4.    VIVUS agrees to inform CHINOIN about its main findings on these
               validation batches of MUSE as well as to notify CHINOIN in a
               timely manner regarding regulatory submissions and their outcome.

     2.7 The Parties agree that VIVUS shall not be required to purchase from
CHINOIN any amount of the Product in the remainder of calendar year 2002 and
VIVUS shall have only the following firm commitments to purchase the Product
from CHINOIN during the validity of the Agreement as extended according to
Section 2.3 of this Amendment Three:

     2.7.1.    VIVUS agrees to take delivery of [*] of the Product during the
               seventh Agreement Year in the following schedule and under the
               conditions stipulated herein.

               1.   [*] immediately upon availability in January/February 2003
               2.   Approximately [*] in October 2003
               3.   Approximately [*], up to [*]total in December 2003

               The first delivery to VIVUS in 2003 will consist of [*] from each
               of the [*] of Product manufactured by CHINOIN with the modified
               process as described in Section 2.4.1 of this Amendment Three.
               The second delivery may contain further quantities of these [*]
               still on stock at CHINOIN at the time of shipment or from further
                [*] or [*]   manufactured with the same modified process of
               CHINOIN. CHINOIN agrees to refrain from shipping residual tails
               of [*] below [*].

     2.7.2.    Parties agree that the obligation of VIVUS to take the [*]
               deliveries is subject to European approval as set forth in
               Section 2.6.3 and to US FDA approval of the supplement to VIVUS'
               NDA of MUSE as set forth in Section 2.6.2 of this Amendment
               Three.
<PAGE>

     2.7.3.    Within five (5) working days after execution of this Amendment
               Three, VIVUS agrees to issue a Purchase Order for the delivery of
               [*] of Product with reference to conditions stipulated in this
               Amendment Three.

     2.7.4.    VIVUS will place with CHINOIN [*] of its orders for the Product
               (based on mass) until VIVUS accepts delivery from CHINOIN the [*]
               of the Product referred to in Section 2.7.1. In no event will
               CHINOIN be obligated to supply more than [*] of Product in the
               seventh Agreement Year.

     2.7.5.    From the eighth Agreement Year of this Amendment Three onward,
               VIVUS agrees to place not less than [*] of its orders for the
               Product (based on mass) from CHINOIN after having completed all
               of its purchasing obligations as detailed above in Sections 2.71,
               2.7.2, 2.7.3 and 2.7.2 of this Amendment Three. In no event will
               CHINOIN be obligated to supply more than [*] of Product annually.

     2.7.6.    Section 2.12 of the Agreement is hereby restated to read as
               follows:

               2.12 Minimum Quantities

               2.12.1    VIVUS agrees that the quantity of Product purchased
                         from CHINOIN shall in no event fall below the minimum
                         quantity of [*] in the eighth and ninth Agreement
                         Years. This undertaking is not subject to any waiver
                         due to decrease of the consumption of the Product.

               2.12.2    The Parties will negotiate the minimum purchasing
                         stipulations for the tenth, eleventh and twelfth
                         Agreement Years at the end of ninth Agreement Year.
                         Should the Parties fail to reach new minimum purchasing
                         stipulations at the end of ninth Agreement Year, the
                         purchasing stipulations valid in the ninth Agreement
                         Year shall remain in force for the tenth, eleventh and
                         twelfth Agreement Years.

     2.8 Non-fulfillment

     2.8.1.    In the event CHINOIN is unable to fulfil its obligations within
               three (3) months from the deadline indicated in Section 2.4.2 of
               this Amendment Three, VIVUS will have the right to place orders
               with other supplier(s) in quantities not exceeding the quantity
               scheduled for the time in question stipulated in Section 2.7.1 of
               this Amendment Three until the time CHINOIN completes the
               fulfillment of its referred obligations.

               Thereafter, VIVUS will place with CHINOIN [*] of its orders for
               the Product until the [*] stipulated in Section 2.7.1 is
               delivered in full.

               The delay of VIVUS taking deliveries of the [*] stipulated in
               Section 2.4.1 for any reason will create no right for either of
               the Parties to change the price of this [*] as stipulated for the
               seventh Agreement Year in Section 2.9 of this Amendment Three.

               VIVUS agrees that the measures to postpone taking delivery from
               CHINOIN and/or to order quantities from other suppliers
               proportionally as stipulated in Section 2.8.1 will satisfy in
               full any and all of CHINOIN's obligations and VIVUS will not be
               entitled to claim compensations or losses due to the above delay,
               if any.

     2.8.2.    Notwithstanding Section 2.7.2 of this Amendment Three, in the
               event VIVUS is unable to acquire the approval of its supplement
               to its NDA, as described in Section 2.6 of this Amendment Three,
               due to reasons
<PAGE>

               unquestionably not attributable to CHINOIN, VIVUS shall be
               obligated to take the [*] and pay their value in full.

               Parties agree that the lack of any question on the Product by the
               FDA during the Amendment approval procedure or the lack of
               reasons referring to the Product in a regulatory decision denying
               the approval are reasons unquestionably not attributable to
               CHINOIN without any further evidence in case of inability of
               VIVUS to acquire the approval in question.

     2.9 Section 2.7 of the Agreement as modified by Amendment One is hereby
amended in its entirety to read as follows:

               2.7       Price The price to be paid by VIVUS per gram of the
                         Product ordered by VIVUS shall be based upon the
                         quantities of the Product ordered by VIVUS for delivery
                         during the particular Agreement Year, as follows:

               2.7.1     Quantity Ordered for Delivery

                         During the seventh Agreement Year            U.S. $/[*]
                         ---------------------------------            ----------
                         All quantities up to [*]                       $[*]
                         Quantities in excess of [*], if any
                         up to [*]                                      $[*]
                         Quantities in excess of [*], if any
                         up to [*]                                      $[*]

               2.7.2     Quantity Ordered for Delivery

                         During the eight and ninth Agreement Year    U.S. $/[*]
                         -----------------------------------------    ----------
                         First [*]
                         "Minimum Annual Quantity"                      $[*]
                         Quantities in excess of [*],
                         up to [*]                                      $[*]
                         Quantities in excess of [*],
                         up to [*]                                      $[*]
                         Quantities in excess of [*],
                         up to [*]                                      $[*]
                         Quantities in excess of [*],
                         up to [*]                                      $[*]
                         Quantities in excess of [*], if any            $[*]

               2.7.3     The Parties will negotiate the price stipulations for
                         the tenth, eleventh and twelfth Agreement Years at the
                         end of ninth Agreement Year. Should the Parties fail to
                         reach new price stipulations at the end of ninth
                         Agreement Year, the price stipulations valid in the
                         ninth Agreement Year shall remain in force for the
                         tenth, eleventh and twelfth Agreement Years.

                         It is understood that the foregoing prices are based
                         upon the total cumulative quantities ordered by VIVUS
                         for delivery during the particular Agreement Year, and
                         not only on the size of the particular order or
                         delivery. It is also understood that the prices are for
                         the incremental quantities.
<PAGE>

3.   ENTIRE AGREEMENT. The Agreement and any Exhibits and Addenda thereto
together with this Amendment Three and Amendment One and Amendment Two
constitute the entire agreement between the Parties with respect to the subject
matter thereof and supersede all prior and contemporaneous communications,
representations, agreements or understandings, either written or oral, between
the Parties.

IN WITNESS WHEREOF, the parties hereto have executed this Amendment Three.

VIVUS, INC.                              CHINOIN PHARMACEUTICAL AND
                                         CHEMICAL WORKS CO., LTD.

By: /s/                                  By: /s/
   --------------------------------         --------------------------------

Name: Terry Nida                         Name: Patrick CHOCAT
      -----------------------------            -----------------------------

Title: Vice President                    Title: Managing Director
       ----------------------------            -----------------------------


                                         By: /s/
                                            --------------------------------
                                         Name: Eric-Yves LILLE
                                               -----------------------------
                                         Title: VP Administration & Finance
                                               -----------------------------


* Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has already been granted with respect to
the omitted portions.
<PAGE>



CHINOIN - VIVUS                    EXHIBIT A                         CHINOIN.DOC
AMENDMENT THREE TO THE                                         F-OCTOBER 8, 2002
MANUFACTURING AGREEMENT
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