Verteporfin: Difference between revisions

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			{{Short description\|Pharmaceutical drug}}
⚫	{{no ~~references~~\|date=December ~~2011~~}}

	{{Drugbox		{{Drugbox
	\| Verifiedfields = changed		\| Verifiedfields = changed
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	\| IUPAC_name = 3-octacosa-1,3,5,7,9,11(27),12,14,16,18(25),19,21-dodecaen-9-yl]propanoic acid		\| IUPAC_name = 3-octacosa-1,3,5,7,9,11(27),12,14,16,18(25),19,21-dodecaen-9-yl]propanoic acid
	\| image = Verteporfin.svg		\| image = Verteporfin.svg

	<!--Clinical data-->		<!--Clinical data-->
	\| tradename =		\| tradename = Visudyne
	\| Drugs.com = {{drugs.com\|monograph\|verteporfin}}		\| Drugs.com = {{drugs.com\|monograph\|verteporfin}}
	\| MedlinePlus = a607060		\| MedlinePlus = a607060
	\| ~~pregnancy_category~~ =		\| pregnancy_US = C
	\| ~~legal_status~~ =		\| licence_EU = yes
			\| legal_US = Rx-only
	\| routes_of_administration = ]		\| routes_of_administration = ]

	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->
	\| bioavailability =		\| bioavailability =
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	\| metabolism =		\| metabolism =
	\| elimination_half-life =		\| elimination_half-life =

	<!--Identifiers-->		<!--Identifiers-->
	\| CASNo_Ref = {{cascite\|correct\|CAS}}
	\| CAS_number_Ref = {{cascite\|correct\|??}}		\| CAS_number_Ref = {{cascite\|correct\|??}}
	\| CAS_number = 129497-78-5		\| CAS_number = 129497-78-5
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	\| ATC_supplemental =		\| ATC_supplemental =
	\| PubChem = 5362420		\| PubChem = 5362420
	\| DrugBank_Ref = {{drugbankcite\|~~changed~~\|drugbank}}		\| DrugBank_Ref = {{drugbankcite\|correct\|drugbank}}
	\| DrugBank = ~~APRD01290~~		\| DrugBank = DB00460
	\| ChemSpiderID_Ref = {{chemspidercite\|correct\|chemspider}}		\| ChemSpiderID_Ref = {{chemspidercite\|correct\|chemspider}}
	\| ChemSpiderID = 21106402		\| ChemSpiderID = 21106402
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	\| ChEBI = 60775		\| ChEBI = 60775
	\| ChEMBL_Ref = {{ebicite\|changed\|EBI}}		\| ChEMBL_Ref = {{ebicite\|changed\|EBI}}
	\| ChEMBL = ~~1200573~~		\| ChEMBL = 2218885

	<!--Chemical data-->		<!--Chemical data-->
	\| C=41 \| H=42 \| N=4 \| O=8		\| C=41 \| H=42 \| N=4 \| O=8
			\| smiles = COC(=O)CCC=1C(C)=C2C=C6N=C(C=C4NC(=CC3=NC(=CC=1N2)C(CCC(O)=O)=C3C)C(C=C)=C4C)C5=CC=C(C(=O)OC)(C(=O)OC)56C
	\| molecular_weight = 718.794 g/mol
	\| smiles = COC(=O)2C(=C\C=C3\c1cc6nc(cc5nc(cc4nc(cc(n1)23C)C(/C)=C4/CCC(=O)OC)c(CCC(O)=O)c5C)C(/C=C)=C6/C)/C(=O)OC
	\| InChI = 1/C41H42N4O8/c1-9-23-20(2)29-17-34-27-13-10-26(39(49)52-7)38(40(50)53-8)41(27,5)35(45-34)19-30-22(4)25(12-15-37(48)51-6)33(44-30)18-32-24(11-14-36(46)47)21(3)28(43-32)16-31(23)42-29/h9-10,13,16-19,38,43,45H,1,11-12,14-15H2,2-8H3,(H,46,47)/b31-16-,33-18-,34-17-,35-19-/t38-,41+/m0/s1
	\| InChIKey = ZCQHFRFEJXRZDF-YWANUUMDBT
	\| StdInChI_Ref = {{stdinchicite\|correct\|chemspider}}		\| StdInChI_Ref = {{stdinchicite\|correct\|chemspider}}
	\| StdInChI = 1S/C41H42N4O8/c1-9-23-20(2)29-17-34-27-13-10-26(39(49)52-7)38(40(50)53-8)41(27,5)35(45-34)19-30-22(4)25(12-15-37(48)51-6)33(44-30)18-32-24(11-14-36(46)47)21(3)28(43-32)16-31(23)42-29/h9-10,13,16-19,38,43,45H,1,11-12,14-15H2,2-8H3,(H,46,47)/b31-16-,33-18-,34-17-,35-19-/t38-,41+/m0/s1		\| StdInChI = 1S/C41H42N4O8/c1-9-23-20(2)29-17-34-27-13-10-26(39(49)52-7)38(40(50)53-8)41(27,5)35(45-34)19-30-22(4)25(12-15-37(48)51-6)33(44-30)18-32-24(11-14-36(46)47)21(3)28(43-32)16-31(23)42-29/h9-10,13,16-19,38,43,45H,1,11-12,14-15H2,2-8H3,(H,46,47)/b31-16-,33-18-,34-17-,35-19-/t38-,41+/m0/s1
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	}}		}}

	'''Verteporfin''' (trade name '''Visudyne'''), a benzoporphyrin derivative, is a ] used as a ] for ] to eliminate the abnormal ]s in the ] associated with conditions such as the wet form of ]. Verteporfin accumulates in these abnormal blood vessels and, when stimulated by nonthermal red light with a ] of ~~693~~ nm in the presence of ], produces highly reactive short-lived singlet oxygen and other reactive ]s, resulting in local damage to the ] and blockage of the vessels.		'''Verteporfin''' (trade name '''Visudyne'''), a ] derivative, is a ] used as a ] for ] to eliminate the abnormal ]s in the ] associated with conditions such as the wet form of ]. Verteporfin accumulates in these abnormal blood vessels and, when stimulated by nonthermal red light with a ] of 689 nm<ref>{{cite web\|url=http://www.bausch.com/Portals/109/-/m/BL/United%20States/Files/Package%20Inserts/Pharma/visudyne-package-insert.pdf \|title=Visudyne package insert}}</ref> in the presence of ], produces highly reactive short-lived singlet oxygen and other reactive ]s, resulting in local damage to the ] and blockage of the vessels.<ref name="Drugs.com">Verteporfin {{drugs.com\|monograph\|verteporfin}}</ref><ref name=Scott2000>{{cite journal \| vauthors = Scott LJ, Goa KL \| title = Verteporfin \| journal = Drugs & Aging \| volume = 16 \| issue = 2 \| pages = 139–46; discussion 147–8 \| date = February 2000 \| pmid = 10755329 \| doi = 10.2165/00002512-200016020-00005 \| s2cid = 260491296 }}</ref>

	Verteporfin is also used ] for the treatment of ].		Verteporfin is also used ] for the treatment of ].<ref name=offlab>{{cite journal \| vauthors = Karim SP, Adelman RA \| title = Profile of verteporfin and its potential for the treatment of central serous chorioretinopathy \| journal = Clinical Ophthalmology \| volume = 7 \| pages = 1867–75 \| year = 2013 \| pmid = 24092965 \| pmc = 3788817 \| doi = 10.2147/OPTH.S32177 \| doi-access = free }}</ref>

	==Administration==		==Administration==
			Verteporfin is usually injected ]ly into the largest arm vein.<ref name=verte2018Dec/> It is injected at a dose of 6 mg/m2 and light-activated.<ref name=verte2018Dec>{{Citation \| last = Mohede \| first = Daan C.J. \| title = Verteporfin as a Medical Treatment in Peyronie's Disease \| journal = Sex Med \| date = 28 September 2018 \| volume = 6 \| issue = 4 \| pages = 302–308 \| doi = 10.1016/j.esxm.2018.08.002 \| pmid = 30274909 \| pmc = 6302152 \| language = English }}</ref> It is usually given 15 minutes before laser treatment.<ref name="Drugs.com" /> This dose can be repeated 4 times per year.<ref name=verte2018Dec/>
	Verteporfin is given ]ly, within 15 minutes before laser treatment.

			==Contraindications==
		⚫	{{expand section\|date=December 2024}}
			].<ref name="Drugs.com" />

	==Side effects==		==Side effects==
	Most ~~commonly,~~ blurred vision. Also, photosensitivity; it is advised to avoid exposure to sunlight and unscreened lighting until 48 hours after ~~the~~ ~~injection~~ ~~of verteporfin~~.		Most common side effects are blurred vision, headache, and local effects at the injection site. Also, ]; it is strictly advised to avoid exposure to sunlight and unscreened lighting until 48 hours after verteporfin administration.<ref name="Drugs.com" />

			Dogs and rats have been treated with inactivated daily doses 32–70 times higher than the dose advised for humans.<ref name=verte2018Dec/> The 4 weeks of treatment resulted in mild extravascular hemolysis and hematopoiesis in the animals.<ref name=verte2018Dec/>

			== Light-activated cytotoxicity ==
			Used by itself, the clinical recommended dose for verteporfin is not ] to human tissue.<ref name=cyto2023>{{cite web
			\| title = SUMMARY OF PRODUCT CHARACTERISTICS
			\|quote = By itself, the clinically recommended dose of verteporfin is not cytotoxic. It produces cytotoxic agents only when activated by light in the presence of oxygen. When energy absorbed by the porphyrin is transferred to oxygen, highly reactive short-lived singlet oxygen is generated. Singlet oxygen causes damage to biological stmctures within the diffusion range, leading to local vascular occlusion, cell damage and, under certain conditions, cell death.
			\| url = https://www.ema.europa.eu/en/documents/product-information/visudyne-epar-product-information_en.pdf
			\| website = ema.europa.eu
			\| date = 13 December 2023
			\|archive-url = https://web.archive.org/web/20231213134659/https://www.ema.europa.eu/en/documents/product-information/visudyne-epar-product-information_en.pdf
			\| access-date = 13 December 2023\|archive-date = 2023-12-13
			}}</ref> Though under light activation, in the presence of oxygen, it can form cytotoxic agents inside the tissue.<ref name=cyto2023/> The agents form when the porphyrin absorbs enough light to generate a reactive but short-lived singlet oxygen.<ref name=cyto2023/> The brief singlet oxygen can micro damage biological structures, leading to a local vascular occlusion.<ref name=cyto2023/>

			== Interactions ==

			Verteporfin is known to interact with the herbal remedy ] (''Tanacetum parthenium''), the latter of which seems to act as an antagonist to verteporfin for unknown reasons. Taking the two substances simultaneously is inadvisable.<ref>{{cite web \|url=https://www.drugs.com/drug-interactions/feverfew-with-verteporfin-2368-0-2298-0.html \|title=Feverfew and Verteporfin Interactions \| work = Drugs.com \|access-date=14 April 2015}}</ref>

			Verteporfin does not appear to be metabolized by ] enzymes, therefore not affecting ] metabolism of other drugs.<ref name="Prescribing info">{{cite web \|title=Visudyne (verteporfin for injection) prescribing information \|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021119s027lbl.pdf \|website=FDA \|access-date=12 April 2021}}</ref>

			==Shortages==
			In May 2020, a low manufacturing capacity caused disruption.<ref name=shortage/> This affected the usage of verteporfin among providers and patients in Europe.<ref name=shortage>{{cite web \| url = https://www.ema.europa.eu/en/documents/shortage/shortage-visudyne-verteporfin-supply-shortage_en.pdf \| title = Shortage of Visudyne (verteporfin) \| last = EMA \| date =5 November 2021 \| website =ema.europa.eu \| access-date = 1 February 2022 }}</ref> The EMA expected normal manufacturing to return by the first quarter 2022.<ref name=shortage/>

			== Off-label use in retinopathy ==
			Verteporfin may be used off-label for treating central serous retinopathy.<ref name=offlab/><ref name=shortage/>

			== References ==
			{{reflist}}

	==External links ==		==External links ==
	*		* {{cite web \| url = http://www.visudyne.com/ \| work = Novartis \| title = Visudyne }}
	*

	{{Ocular vascular disorder agents}}		{{Ocular vascular disorder agents}}
			{{Intracellular chemotherapeutic agents}}
	{{Intracellular_chemotherapeutic_agents}}

	]		]
	]		]
			]

	]

Latest revision as of 19:41, 9 December 2024

Pharmaceutical drug Pharmaceutical compound

Verteporfin
Clinical data

Trade names	Visudyne
AHFS/Drugs.com	Monograph
MedlinePlus	a607060
License data	EU EMA: by INN
Routes of administration	Intravenous
ATC code	S01LA01 (WHO)
Legal status
Legal status	US: ℞-only
Identifiers
IUPAC name 3-octacosa-1,3,5,7,9,11(27),12,14,16,18(25),19,21-dodecaen-9-yl]propanoic acid
CAS Number	129497-78-5
PubChem CID	5362420
DrugBank	DB00460
ChemSpider	21106402
UNII	0X9PA28K43
KEGG	D01162
ChEBI	CHEBI:60775
ChEMBL	ChEMBL2218885
CompTox Dashboard (EPA)	DTXSID2045604
Chemical and physical data
Formula	C₄₁H₄₂N₄O₈
Molar mass	718.807 g·mol
3D model (JSmol)	Interactive image
SMILES COC(=O)CCC=1C(C)=C2C=C6N=C(C=C4NC(=CC3=NC(=CC=1N2)C(CCC(O)=O)=C3C)C(C=C)=C4C)C5=CC=C(C(=O)OC)(C(=O)OC)56C
InChI InChI=1S/C41H42N4O8/c1-9-23-20(2)29-17-34-27-13-10-26(39(49)52-7)38(40(50)53-8)41(27,5)35(45-34)19-30-22(4)25(12-15-37(48)51-6)33(44-30)18-32-24(11-14-36(46)47)21(3)28(43-32)16-31(23)42-29/h9-10,13,16-19,38,43,45H,1,11-12,14-15H2,2-8H3,(H,46,47)/b31-16-,33-18-,34-17-,35-19-/t38-,41+/m0/s1 Key:ZCQHFRFEJXRZDF-YWANUUMDSA-N
(what is this?) (verify)

Verteporfin (trade name Visudyne), a benzoporphyrin derivative, is a medication used as a photosensitizer for photodynamic therapy to eliminate the abnormal blood vessels in the eye associated with conditions such as the wet form of macular degeneration. Verteporfin accumulates in these abnormal blood vessels and, when stimulated by nonthermal red light with a wavelength of 689 nm in the presence of oxygen, produces highly reactive short-lived singlet oxygen and other reactive oxygen radicals, resulting in local damage to the endothelium and blockage of the vessels.

Verteporfin is also used off-label for the treatment of central serous retinopathy.

Administration

Verteporfin is usually injected intravenously into the largest arm vein. It is injected at a dose of 6 mg/m2 and light-activated. It is usually given 15 minutes before laser treatment. This dose can be repeated 4 times per year.

Contraindications

This section needs expansion. You can help by adding to it. (December 2024)

Porphyria.

Side effects

Most common side effects are blurred vision, headache, and local effects at the injection site. Also, photosensitivity; it is strictly advised to avoid exposure to sunlight and unscreened lighting until 48 hours after verteporfin administration.

Dogs and rats have been treated with inactivated daily doses 32–70 times higher than the dose advised for humans. The 4 weeks of treatment resulted in mild extravascular hemolysis and hematopoiesis in the animals.

Light-activated cytotoxicity

Used by itself, the clinical recommended dose for verteporfin is not cytotoxic to human tissue. Though under light activation, in the presence of oxygen, it can form cytotoxic agents inside the tissue. The agents form when the porphyrin absorbs enough light to generate a reactive but short-lived singlet oxygen. The brief singlet oxygen can micro damage biological structures, leading to a local vascular occlusion.

Interactions

Verteporfin is known to interact with the herbal remedy feverfew (Tanacetum parthenium), the latter of which seems to act as an antagonist to verteporfin for unknown reasons. Taking the two substances simultaneously is inadvisable.

Verteporfin does not appear to be metabolized by Cytochrome P450 enzymes, therefore not affecting Cytochrome P450 metabolism of other drugs.

Shortages

In May 2020, a low manufacturing capacity caused disruption. This affected the usage of verteporfin among providers and patients in Europe. The EMA expected normal manufacturing to return by the first quarter 2022.

Off-label use in retinopathy

Verteporfin may be used off-label for treating central serous retinopathy.

References

"Visudyne package insert" (PDF).
^ Verteporfin Monograph
Scott LJ, Goa KL (February 2000). "Verteporfin". Drugs & Aging. 16 (2): 139–46, discussion 147–8. doi:10.2165/00002512-200016020-00005. PMID 10755329. S2CID 260491296.
^ Karim SP, Adelman RA (2013). "Profile of verteporfin and its potential for the treatment of central serous chorioretinopathy". Clinical Ophthalmology. 7: 1867–75. doi:10.2147/OPTH.S32177. PMC 3788817. PMID 24092965.
^ Mohede, Daan C.J. (28 September 2018), "Verteporfin as a Medical Treatment in Peyronie's Disease", Sex Med, 6 (4): 302–308, doi:10.1016/j.esxm.2018.08.002, PMC 6302152, PMID 30274909
^ "SUMMARY OF PRODUCT CHARACTERISTICS" (PDF). ema.europa.eu. 13 December 2023. Archived from the original (PDF) on 2023-12-13. Retrieved 13 December 2023. By itself, the clinically recommended dose of verteporfin is not cytotoxic. It produces cytotoxic agents only when activated by light in the presence of oxygen. When energy absorbed by the porphyrin is transferred to oxygen, highly reactive short-lived singlet oxygen is generated. Singlet oxygen causes damage to biological stmctures within the diffusion range, leading to local vascular occlusion, cell damage and, under certain conditions, cell death.
"Feverfew and Verteporfin Interactions". Drugs.com. Retrieved 14 April 2015.
"Visudyne (verteporfin for injection) prescribing information" (PDF). FDA. Retrieved 12 April 2021.
^ EMA (5 November 2021). "Shortage of Visudyne (verteporfin)" (PDF). ema.europa.eu. Retrieved 1 February 2022.

External links

"Visudyne". Novartis.

v t e Ophthalmologicals: ocular vascular disorder agents (S01L)
Antineovascularisation agents	Aflibercept Anecortave Bevacizumab Brolucizumab Faricimab Pegaptanib Ranibizumab Verteporfin

Intracellular chemotherapeutic agents / antineoplastic agents (L01)

SPs/MIs
(M phase)

Block microtubule assembly	Vinca alkaloids (Vinblastine Vincristine Vindesine Vinflunine Vinorelbine)
Block microtubule disassembly	Taxanes (Cabazitaxel Docetaxel Larotaxel Ortataxel Paclitaxel Tesetaxel) Epothilones (Ixabepilone)

DNA replication
inhibitor

DNA precursors/
antimetabolites
(S phase)

Folic acid	Dihydrofolate reductase inhibitor (Aminopterin Methotrexate Pemetrexed Pralatrexate) Thymidylate synthase inhibitor (Pemetrexed Raltitrexed)
Purine	Adenosine deaminase inhibitor (Pentostatin) Halogenated/ribonucleotide reductase inhibitors (Cladribine Clofarabine Fludarabine) Nelarabine Rabacfosadine Thiopurine (Mercaptopurine Tioguanine)
Pyrimidine	Thymidylate synthase inhibitor (Capecitabine Carmofur Doxifluridine Floxuridine Fluorouracil Tegafur (+gimeracil/oteracil)) DNA polymerase inhibitor (Cytarabine +daunorubicin) Ribonucleotide reductase inhibitor (Gemcitabine) Hypomethylating agent (Azacitidine Decitabine)
Deoxyribonucleotide	Ribonucleotide reductase inhibitor (Hydroxycarbamide)

Topoisomerase inhibitors
(S phase)

I	Camptotheca (Belotecan Camptothecin Cositecan Etirinotecan pegol Exatecan Gimatecan Irinotecan Lurtotecan Rubitecan Silatecan Topotecan)
II	Podophyllum (Etoposide Teniposide)
II+Intercalation	Anthracyclines (Aclarubicin Amrubicin Daunorubicin (+cytarabine) Doxorubicin Epirubicin Idarubicin Pirarubicin Valrubicin Zorubicin) Anthracenediones (Losoxantrone Mitoxantrone Pixantrone) Amsacrine Bisantrene Crisnatol Menogaril

Crosslinking of DNA
(CCNS)

Alkylating	Nitrogen mustards: Bendamustine Chlormethine Cyclophosphamide (Ifosfamide Trofosfamide) Chlorambucil Melphalan (Melphalan flufenamide) Prednimustine Uramustine Nitrosoureas: Carmustine Fotemustine Lomustine (Semustine) Nimustine Ranimustine Streptozocin Alkyl sulfonates: Busulfan (Mannosulfan Treosulfan) Aziridines: Carboquone Thiotepa Triaziquone Triethylenemelamine
Platinum-based	Carboplatin Cisplatin Dicycloplatin Nedaplatin Oxaliplatin Satraplatin
Nonclassical	Altretamine Hydrazines (Procarbazine) Etoglucid Mitobronitol Pipobroman Triazenes (Dacarbazine Mitozolomide Temozolomide)
Intercalation	Streptomyces (Dactinomycin Bleomycin Mitomycins Plicamycin)

Photosensitizers/PDT

Other

Enzyme inhibitors	FI (Tipifarnib) CDK inhibitors (Abemaciclib Alvocidib Palbociclib Ribociclib Seliciclib) PrI Bortezomib Carfilzomib Oprozomib Ixazomib PhI (Anagrelide) IMPDI (Tiazofurin) LI (Masoprocol) PARP inhibitor (Fuzuloparib Niraparib +abiraterone acetate Olaparib Rucaparib) HDAC (Belinostat Entinostat Panobinostat Romidepsin Vorinostat) PIKI (Pi3K) (Alpelisib Copanlisib Duvelisib Idelalisib Inavolisib Umbralisib) IDH (Enasidenib Ivosidenib Olutasidenib Vorasidenib)
Receptor antagonists	ERA (Atrasentan) Retinoid X receptor (Bexarotene) Sex steroid (Testolactone)
Other/ungrouped	Adagrasib Aflibercept Arsenic trioxide Asparagine depleters (Asparaginase/Pegaspargase) Axicabtagene ciloleucel Belzutifan Bexarotene Brexucabtagene autoleucel Celecoxib Ciltacabtagene autoleucel Demecolcine Denileukin diftitox Eflornithine Elesclomol Elsamitrucin Epacadostat Eribulin Estramustine Glasdegib Idecabtagene vicleucel Imetelstat Lifileucel Lisocabtagene maraleucel Lonidamine Lucanthone Lurbinectedin Mitoguazone Mitotane Nadofaragene firadenovec Navitoclax Obecabtagene autoleucel Oblimersen Omacetaxine mepesuccinate Plitidepsin Tabelecleucel Retinoids (Alitretinoin Tretinoin) Selinexor Sitimagene ceradenovec Sotorasib Tagraxofusp Talimogene laherparepvec Tazemetostat Tebentafusp Tiazofurine Tigilanol tiglate Tisagenlecleucel Trabectedin Veliparib Venetoclax Verdinexor Vosaroxin

WHO-EM
Withdrawn from market
Clinical trials:
- Phase III
- Never to phase III

Categories: