5-Iodo-2′-deoxyuridine

354.1

354.10

30397

200-207-8

LGP81V5245

DTXSID2045238

C563

Crystals from water, triclinic

D - Dermatologicals|J - Antiinfectives for systemic use|S - Sensory organs

2934999090

99.1

-1

White to slightly beige Crystalline Powder

2.1±0.1 g/cm3

263 °C

30 ° (C=1, 1mol/L NaOH)

H2O: 1.6 g/L (20 ºC)

2-8°C

LD50 i.p. in mice: 2.5 g/kg (Prusoff, 1979)

280 º (c=1,1M NaOH)

pH of 0.1% aqueous soln, about 6

pKa = 8.25 (imide nitrogen)

NONH for all modes of transport

3

45-46-61-40-68-62-36/37/38-63

53-45-36-22-36/37-26

YU7700000

T,Xn

Bulk: No changes were found in material stored at room temperature and at 60 ° C for 28 days. Solution: An aqueous solution (2 mg/mL) shows no decomposition after 24 hours at room temperature (UV and paper chromatography).

P280-P305 + P351 + P338

H315-H319-H335-H341-H361

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl idoxuridine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Warning|H315 (89.36%): Causes skin irritation [Warning Skin corrosion/irritation]|P201, P202, P261, P264, P271, P280, P281, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 47 companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Hypersensitivity or increased sensitivity of eyes to light. LD50=3080 mg/kg (orally in mice).

Concurrent use of boric acid with idoxuridine formulations is not recommended; boric acid may interact with inactive ingredients in some idoxuridine formulations, resulting in precipitate formation; in addition, boric acid may interact with preservatives, especially higher concentrations of thimerosal, in other idoxuridine formulations, resulting in increased ocular toxicity.

LD50 Mouse ip 2.5 g/kg

Patients sensitive to iodine or iodine-containing preparations may be sensitive to this medication also.

It is not known whether idoxuridine is distributed into breast milk.

For use in keratoconjunctivitis and keratitis caused by herpes simplex virus.

Antiviral|Idoxuridine is indicated in the treatment of keratitis caused by herpes simplex virus (HSV). /Included in US product label/|Idoxuridine is indicated in the treatment of keratitis caused by vaccinia virus. /Not included in US product label/|Idoxuridine is used in the treatment of keratoconjunctivitis caused by herpes simplex virus (HSV). /Not included in US product label/|Idoxuridine has no effect on accumulated scarring, vascularization, or progressive loss of vision that may result from the infection. It also has no effect on corneal inflammation that may follow HSV keratitis when the virus is absent, nor on adenoviral keratoconjunctivitis. /Not included in US product label/

Patients sensitive to iodine or iodine-containing preparations may be sensitive to this medication also.|The following side/adverse effects have been selected on the basis of their potential clinical significance: Incidence less frequent /include/ Hypersensitivity (itching, redness, swelling, pain, or other sign of irritation not present before therapy), or increased sensitivity of eyes to light; Incidence rare: Corneal clouding (blurring, dimming, or haziness of vision).|FDA Pregnancy Risk Category: C /RISK CANNOT BE RULED OUT. Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk./|The ... toxicity of topical applications of 30% idoxuridine in dimethyl sulfoxide, dimethyl sulfoxide alone, or saline in 96 recurrent and 39 first episodes of genital herpes simplex virus (HSV) infection were compared. ...Complications in patients given idoxuridine in dimethyl sulfoxide included local burning, generalized contact dermatitis, and vulvar carcinoma in situ. Thirty percent idoxuridine in dimethyl sulfoxide has no effect on clinical manifestations of genital HSV infection and may be hazardous.

Resistance to idoxuridine readily develops in vitro and occurs in viral isolates recovered from idoxuridine -treated patients with HSV keratitis.

In chemical structure idoxuridine closely approximates the configuration of thymidine, one of the four building blocks of DNA (the genetic material of the Herpes virus). As a result, idoxuridine is able to replace thymidine in the enzymatic step of viral replication or "growth". The consequent production of faulty DNA results in a pseudostructure which cannot infect or destroy tissue. In short, by pre-empting a vital building block in the genetic material of the Herpes simplex virus, Herplex-D topical solution destroys the infective and destructive capacity of the viral material. The virus infected cell may only be attacked during the period of active synthesis of DNA. This occurs early in the development of the Herpes simplex lesion, but at different times in different cells. Therefore, ideally, the affected area should remain saturated with the antiviral agent.

Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. (See all compounds classified as Antiviral Agents.)|Compounds that inhibit cell production of DNA or RNA. (See all compounds classified as Nucleic Acid Synthesis Inhibitors.)

Systemic absorption is unlikely following ocular administration even when nasolacrimal secretions are swallowed, since vidarabine is rapidly deaminated in the gastrointestinal tract.|Idoxuridine penetrates the cornea poorly and therefore is ineffective in the treatment of iritis or deep stromal infections.|Idoxuridine crosses the placenta. Studies in humans have not been done.|It is not known whether idoxuridine is distributed into breast milk. However, problems in humans have not been documented.|A reproducible microbiologic assay of microgram quantities of idoxuridine (IDU) in serum, urine, or cerebrospinal fluid is presented. The antiviral assay is not interfered with by type-specific antibody or interferon. During slow intravenous infusions of idox-uridine (4 mg/min) in patients with suspected diagnoses of Herpesvirus hominis encephalitis, the rate of inactivation and/or removal of drug exceeded its administration. During several rapid infusions of idoxuridine (50 mg/min) significant quantities of the drug were found in serum, urine, and cerebrospinal fluid. Idoxuridine is not significantly bound to serum proteins and is not deiodinated in fresh serum or urine in vitro to inactive products (iodouracil, uracil, iodide). It is rapidly excreted into the urine. Inactivation of IDU occurs in tissues. This antiviral assay of IDU in body fluids should be applicable to other viruses and potential antiviral agents.

Idoxuridine is rapidly inactivated by deaminases or nucleotidases.

Idoxuridine acts as an antiviral agent by inhibiting viral replication by substituting itself for thymidine in viral DNA. This in turn inhibits thymidylate phosphorylase and viral DNA polymerases from properly functioning. The effect of Idoxuridine results in the inability of the virus to reproduce or to infect/destroy tissue.|Idoxuridine, which closely resembles thymidine, inhibits thymidylic phosphorylase and specific DNA polymerases, which are necessary for the incorporation of thymidine into viral DNA. Idoxuridine is incorporated in place of thymidine into viral DNA, resulting in faulty DNA and the inability to infect or destroy tissue or to reproduce. Idoxuridine is incorporated into mammalian DNA as well.

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ A total of 45 of 60 patients with herpes zoster previously treated with topical idoxuridine 5-40% in dimethylsulfoxide were patch tested 2 years later with idoxuridine 0.5% and 5% in petrolatum. Three (7%) showed positive reactions. Idoxuridine is considered a weak sensitizer, but in strong concentrations and in active solvents, which increases absorption, there seems to be a risk of sensitization.|/CASE REPORTS/ Four patients had idoxuridine-induced conjunctival cicatrization similar to ocular cicatricial pemphigoid develop, but in the treated eye only. Three of the four patients had chronic, recurrent herpes simplex epithelial and stromal keratitis. The fourth patient had Sjogren's syndrome. All received idoxuridine (0.1% drops and/or 0.5% ointment) and topical corticosteroids from one to 3 1/2 years. Substantial morbidity resulted that included visual loss, stromal ulceration, corneal scarring, and keratinization. Conjunctival biopsy specimens showed cicatrization with a mixed inflammatory cell reaction and absence of goblet cells. Results of direct immunofluorescent microscopy of the conjunctiva were either negative or nonspecific for autoantibody. No circulating autoantibody was detected in any of the four patients.|/CASE REPORTS/ A case of herpes encephalitis diagnosed by brain biopsy and treated with 5-iodo-2-deoxyuridine (IDU) is presented. The infection occurred in a previously well 19-year-old female patient. Plasma and cerebrospinal fluid (CSF) uptake of the substance was determined using 125I labelled IDU. Top CSF levels of IUD and metabolites of less than 4 microgram/mL, about 1/10 of the corresponding plasma level, were obtained after 6 hours of continuous infusion. The result is discussed and compared with a similar study made on 5 healthy beagle dogs where in addition the levels obtained in various parts of the brain were determined. In the animal experiment a mean value of 2.5 microgram/ml of IDU and metabolites was obtained in the CSF after 8 hours, less than 1/20 of the plasma level. The levels in brain tissue were only slightly higher than in the CSF.

123I-Labeled Idoxuridine

U.S., 0.1% (Rx) [Herplex Liquifilm (polyvinyl alcohol 1.4%, benzalkonium chloride); Stoxil (thimerosal 1:50,000)]; Canada, 0.1% (Rx) [Herplex Liquifilm (polyvinyl alcohol 1.4%, benzalkonium chloride 0.004%); Stoxil (thimerosal 1:50,000)]. /Ophthalmic Solution USP/|U.S., 0.5% (Rx) [Stoxil]; Canada, 0.5% (Rx) [Stoxil]. /Ophthalmic Ointment USP/

Uridine, 2'-deoxy-5-iodo-: ACTIVE

Analyte: idoxuridine; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: idoxuridine; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards|Analyte: idoxuridine; matrix: chemical purity; procedure: dissolution in neutralized dimethylformamide; addition of thymol blue in methanol as indicator; titration with sodium methoxide to a blue endpoint|Analyte: idoxuridine; matrix: pharmaceutical preparation (ophthalmic ointment; ophthalmic solution); procedure: ultraviolet absorption spectrophotometry at 320 nm and 283 nm with comparison to standards (chemical identification and chemical purity)|For more Analytic Laboratory Methods (Complete) data for IDOXURIDINE (8 total), please visit the HSDB record page.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients