Verteporfin

Verteporfin
Clinical data
Trade namesVisudyne
AHFS/Drugs.comMonograph
MedlinePlusa607060
License data
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
Identifiers
  • 3-[(23S,24R)-14-ethenyl-5-(3-methoxy-3-oxopropyl)-22,23-bis(methoxycarbonyl)-4,10,15,24-tetramethyl-25,26,27,28-tetraazahexacyclo[16.6.1.13,6.18,11.113,16.019,24]octacosa-1,3,5,7,9,11(27),12,14,16,18(25),19,21-dodecaen-9-yl]propanoic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC41H42N4O8
Molar mass718.807 g·mol−1
3D model (JSmol)
  • 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@@H](C(=O)OC)[C@]56C
  • 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 checkY
  • Key:ZCQHFRFEJXRZDF-YWANUUMDSA-N checkY
 ☒NcheckY (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[1] 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.[2][3]

Verteporfin is also used off-label for the treatment of central serous retinopathy.[4]

Administration

Verteporfin is usually injected intravenously into the largest arm vein.[5] It is injected at a dose of 6 mg/m2 and light-activated.[5] It is usually given 15 minutes before laser treatment.[2] This dose can be repeated 4 times per year.[5]

Contraindications

Porphyria.[2]

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.[2]

Dogs and rats have been treated with inactivated daily doses 32–70 times higher than the dose advised for humans.[5] The 4 weeks of treatment resulted in mild extravascular hemolysis and hematopoiesis in the animals.[5]

Light-activated cytotoxicity

Used by itself, the clinical recommended dose for verteporfin is not cytotoxic to human tissue.[6] Though under light activation, in the presence of oxygen, it can form cytotoxic agents inside the tissue.[6] The agents form when the porphyrin absorbs enough light to generate a reactive but short-lived singlet oxygen.[6] The brief singlet oxygen can micro damage biological structures, leading to a local vascular occlusion.[6]

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.[7]

Verteporfin does not appear to be metabolized by Cytochrome P450 enzymes, therefore not affecting Cytochrome P450 metabolism of other drugs.[8]

Shortages

In May 2020, a low manufacturing capacity caused disruption.[9] This affected the usage of verteporfin among providers and patients in Europe.[9] The EMA expected normal manufacturing to return by the first quarter 2022.[9]

Off-label use in retinopathy

Verteporfin may be used off-label for treating a form of retinopathy.[4][9]

References

  1. ^ "Visudyne package insert" (PDF).
  2. ^ a b c d Verteporfin Monograph
  3. ^ 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.
  4. ^ a b 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.
  5. ^ a b c d e 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
  6. ^ a b c d "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.
  7. ^ "Feverfew and Verteporfin Interactions". Drugs.com. Retrieved 14 April 2015.
  8. ^ "Visudyne (verteporfin for injection) prescribing information" (PDF). FDA. Retrieved 12 April 2021.
  9. ^ a b c d EMA (5 November 2021). "Shortage of Visudyne (verteporfin)" (PDF). ema.europa.eu. Retrieved 1 February 2022.