Prevention and treatment of ocular side effects with a cyclosporin

Abstract

Therapeutic methods including administration of cyclosporin to an eye of a mammal in combination with administration of a therapeutically active agent effective for treatment of a cancer to said mammal to treat an ocular condition associated with the use of said therapeutically active agent are disclosed herein.

Claims

1. A method comprising: administering a composition comprising cyclosporin A to a mammal before the mammal receives a therapeutically active agent, wherein the therapeutically active agent comprises docetaxel, and then administering the therapeutically active agent comprising docetaxel to the mammal in need thereof, wherein the method is effective in treating lacrimal duct stenosis in a mammal whose lacrimal duct stenosis is associated with the administration of the therapeutically active agent comprising docetaxel.

2. The method of claim 1, wherein the composition comprises cyclosporin A at a concentration of about 0.05%.

3. The method of claim 2, wherein the composition further comprises castor oil, polysorbate 80, and high molecular weight co-polymers of acrylic acid and a long chain alkyl methacrylate cross-linked with allyl ethers of pentaerythritol.

Description

(1) Although the ocular condition may be associated with any antiviral agent, the following

(2) antiviral agents are contemplated in particular:

(3) Zalcitabine, and

(4) Rimantadine Hydrochloride.

(5) Although the ocular condition may be associated with any chemotherapy agent, the following

(6) chemotherapy agents are contemplated in particular:

(7) Paclitaxel and derivatives thereof, such as Docetaxel

(8) Doxorubicin Hydrochloride,

(9) Irinotecan Hydrochloride,

(10) Fluorouracil,

(11) Imatinib Mesylate, and

(12) Rituximab.

(13) Derivatives of paclitaxel generally include the macrocycle shown below, where derivatives are formed at a hydroxyl moiety.

(14) ##STR00002##

(15) Chemotherapeutic compounds incorporating this structure are thus contemplated. For example, the structures of paclitaxel and docetaxel are shown below.

(16) ##STR00003##

(17) In one embodiment, the chemotherapy agent is docetaxel.

(18) Although the ocular condition may be associated with any immunomodulator, the following

(19) immunomodulators are contemplated in particular:

(20) Interferon alfa-2b, Recombinant

(21) Mycophenolate Mofetil, and

(22) Mycophenolate Mofetil Hydrochloride.

(23) While not intending to limit the scope of the invention in any way, the following therapeutically active agents may cause lacrimal duct stenosis: docetaxel.

(24) While not intending to limit the scope of the invention in any way, the following therapeutically active agents may cause lacrimation:

(25) interferon alfa-2b, recombinant,

(26) doxorubicin hydrochloride,

(27) irinotecan hydrochloride,

(28) fluorouracil,

(29) docetaxel, and

(30) zalcitabine.

(31) While not intending to limit the scope of the invention in any way, the following therapeutically active agents may cause abnormal lacrimation:

(32) mycophenolate mofetil,

(33) mycophenolate mofetil hydrochloride,

(34) imatinib mesylate,

(35) rituximab, and

(36) rimantadine hydrochloride.

(37) While not intending to limit the scope of the invention in any way, the following therapeutically active agents may cause keratitis:

(38) Amantadine Hydrochloride,

(39) Erlotinib,

(40) Bexarotene, and

(41) Voriconazole.

(42) While not intending to limit the scope of the invention in any way, the following therapeutically active agents may cause keratoconjunctivitis:

(43) Capecitabine.

(44) While not intending to limit the scope of the invention in any way, the following therapeutically active agents may cause conjunctivitis:

(45) Risedronate Sodium,

(46) Leflunomide,

(47) Mycophenolate Mofetil,

(48) Oxaliplatin,

(49) Cetuximab,

(50) Ribavirin,

(51) Rituximab,

(52) Basiliximab,

(53) Erlotinib,

(54) Capecitabine,

(55) Doxorubicin Hydrochloride,

(56) Imiquimod,

(57) Amphotericin B, liposomal,

(58) Zolpidem Tartrate,

(59) Glatiramer Acetate,

(60) Epirubicin Hydrochloride,

(61) Saquinavir,

(62) Enfuvirtide,

(63) Imatinib Mesylate,

(64) Gefitinib,

(65) Lamotrigine,

(66) Delavirdine Mesylate,

(67) Rituximab,

(68) Ivermectin,

(69) Palivizumab,

(70) Oseltamivir Phosphate,

(71) Bexarotene,

(72) Docetaxel,

(73) Abacavir Sulfate,

(74) Lamivudine,

(75) Zidovudine,

(76) Voriconazole,

(77) Nevirapine,

(78) Ribavirin, and

(79) Abacavir Sulfate.

(80) Additionally, one or more of the ocular conditions disclosed herein may be associated with the following therapeutically active agents: abacavir sulfate, amantadine hydrochloride, amphotericin B, basiliximab, bexarotene, capecitabine, cetuximab, delavirdine mesylate, docetaxel, doxorubicin hydrochloride, enfuvirtide, epirubicin hydrochloride, erlotinib, fluorouracil, gefitinib, glatiramer acetate, imatinib mesylate, imiquimod, interferon alfa-2b, irinotecan hydrochloride, ivermectin, lamivudine, lamotrigine, leflunomide, mycophenolate mofetil, mycophenolate mofetil hydrochloride, nevirapine, oseltamivir phosphate, oxaliplatin, palivizumab, ribavirin, rimantadine hydrochloride, risedronate sodium, rituximab, saquinavir, voriconazole, zalcitabine, zidovudine, and zolpidem tartrate.

(81) The therapeutically active agent is administered in the usual manner known in the art for the condition being treated.

(82) Alternatively, a therapeutically active agent and cyclosporin A may be administered in a single composition.

(83) Useful compositions are disclosed in the following patent applications, each of which is expressly incorporated by reference herein: U.S. patent application Ser. No. 11/181,409, filed on Jul. 13, 2005; U.S. patent application Ser. No. 11/181,509, filed on Jul. 13, 2005; U.S. patent application Ser. No. 11/181,187, filed on Jul. 13, 2005; U.S. patent application Ser. No. 11/181,178, filed on Jul. 13, 2005; U.S. patent application Ser. No. 11/181,428, filed on Jul. 13, 2005; U.S. patent application Ser. No. 11/255,821, filed on Oct. 19, 2005; U.S. patent application Ser. No. 11/161,218, filed on Jul. 27, 2005; and U.S. Provisional Patent Application Ser. No. 60/727,684, filed on Oct. 17, 2005.

(84) In one embodiment, cyclosporin A is administered in the form of Restasis, available from Allergan, Inc. The cyclosporin A is administered twice a day as indicated on the package insert.

(85) Although there has been hereinabove described pharmaceutical compositions for the purpose of illustrating the manner in which the invention may be used to advantage, it should be appreciated that the invention is not limited thereto. Accordingly, any and all modifications, variations, or equivalent arrangements, which may occur to those skilled in the art, should be considered to be within the scope of the present invention as defined in the appended claims.