Vidarabine

267.24

267.24

226-893-9

627048|404241|91041|247519|87676|80832|70422|7652|7359

Crystals from water|Needles from water

29349990

140

-1.1

White to Off-white Powder

2.1±0.1 g/cm3

257-257.5 °C

362.8±34.3 °C

1.907

soluble in DMF (10 mg/ml), 0.5 M HCl (50 mg/ml), DMSO (53 mg/ml at 25°C), ethanol (<1 mg/ml at 25°C), and water (3 mg/ml at 25°C).

−20°C

6.0X10-15 mm Hg at 25 deg C (est)

Celiac-rat LD50: 1476 mg/kg; Oral-Mouse LD50: 3057 mg/kg

Flammable; burning produces toxic nitrogen oxide fumes

D27 -5° (c = 0.25)

Henry's Law constant = 1.11X10-22 atm-cu cm/mol at 25 °C (est)

Hydroxyl radical reaction rate constant = 2.38X10-10 cu cm/molec-sec at 25 °C (est)

Insoluble in water.

Alcohols and Polyols

VIDARABINE is an organic compound containing both amine and alcohol substituents. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides.

II

6.1(a)

2811

3

63-36/37/38

36/37-36-26

AU6200000

Xn,Xi

Warehouse ventilated, low temperature and dry

Vidarabine ophthalmic ointment should be stored at a temperature less than 40 deg C, preferably between 15-30 deg C; freezing should be avoided.

P281

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.

Proposed regulation to exempt marketing applications for certain antibiotic drug products, including vidarabine, from regulatory provisions governing marketing exclusivity and patents.[Federal Register: January 24, 2000 (Volume 65, Number 15)|The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies discontinued drug products. Vidarabine is included on this list.

Flash point data for this chemical are not available; however it is probably combustible. (NTP, 1992)

|Warning|H361 (100%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]|P201, P202, P281, P308+P313, P405, and P501|Aggregated GHS information provided by 40 companies from 3 notifications to the ECHA C&L Inventory.

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should store this material under freezer conditions. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

Burning, itching, and mild irritation of the affected eye are the most common adverse effects of topical vidarabine therapy.

moderately toxic

Although an interaction has not been clearly established, concurrent administration of vidarabine and allopurinol has been associated with tremors, anemia, nausea, pain, and pruritus in some patients. Animal and in vitro studies suggest that allopurinol may interfere with the metabolism of vidarabine.|Acyclovir and vidarabine both exhibit anti-herpetic activity. Because different mechanisms of action of vidarabine and acyclovir have been reported, /the authors/ analyzed their combined anti-herpetic activity on plaque formation of herpes simplex virus (HSV)-1, HSV-2, and varicella-zoster virus (VZV) by isobolograms. The results indicate that acyclovir and vidarabine have a synergistic effect on wild type HSV-1, HSV-2, and VZV. ...

LD50 Mouse iv 442 mg/kg|LD50 Mouse sc 5086 mg/kg|LD50 Mouse ip 3057 mg/kg|LD50 Mouse oral 7800 ug/kg|For more Non-Human Toxicity Values (Complete) data for VIDARABINE (7 total), please visit the HSDB record page.

Administration of the large volume of iv solution required to solubilize vidarabine may cause fluid overload in patients with CNS infections or impaired renal function. Vidarabine should be used with caution in patients with impaired liver or kidney function and in patients susceptible to fluid overload or cerebral edema. Serum AST (SGOT) concentration, leukocyte and platelet counts, hemoglobin, and hematocrit should be monitored in patients receiving the drug. Vidarabine is contraindicated in patients who are hypersensitive to the drug or any ingredient in the formulation.|The safety and effectiveness in pediatric patients below the age of 2 years have not been established.|A safe dosage of the drug for use in pregnant women has not been established. Vidarabine should be used during pregnancy only if the potential benefits outweigh the possible risks to the fetus. ... It is not known if vidarabine is distributed into milk. Because of the potential for serious adverse reactions from vidarabine in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

NIOSH (NOES Survey 1981-1983) has statistically estimated that 1,307 workers (664 of these are female) are potentially exposed to vidarabine in the US(1).

A nucleoside antibiotic isolated from Streptomyces antibioticus. It has some antineoplastic properties and has broad spectrum activity against DNA viruses in cell cultures and significant antiviral activity against infections caused by a variety of viruses such as the herpes viruses, the VACCINIA VIRUS and varicella zoster virus|Vidarabine has been shown to possess antiviral activity against the following viruses in vitro: Herpes simplex types 1 and 2; vaccinia, varicella-zoster. Except for rhabdovirus and oncornavirus, vidarabine does not display in vitro antiviral activity against other RNA or DNA viruses, including adenovirus.|/EXPTL THER/ When adenovirus causes hemorrhagic cystitis in immunocompromised patients, vidarabine is used for its treatment because therapeutic choice is limited. Although vidarabine has been reported to be effective for these patients, its therapeutic basis has not yet been established. Vidarabine dose-dependently inhibited viral replication as assessed by a yield reduction assay. Viral protein synthesis was dose-dependently inhibited by vidarabine but not at all by acyclovir, and the degree of inhibition by vidarabine was different for each of the viral proteins, ranging from 0-40% of the untreated control. These results indicated the specificity and mechanism of action of vidarabine against adenovirus. The concentration of vidarabine and its metabolite in the bladder is suggested to exhibit effective anti-adenoviral activity in suppressing the replication of adenovirus. Thus, /the authors conclude that their/ results support vidarabine therapy as a possible candidate for adenovirus-induced hemorrhagic cystitis in immunocompromised patients.|/EXPTL THER/ In the present study, effectiveness of topical vidarabine or subsequent 5-fluorouracil (5-FU) administration was examined against persistent genital human papillomavirus (HPV) infection after local surgery. Thirty patients underwent local eradication treatment of uterine cervical intra-epithelial neoplasia (CIN) and stage Ia1 uterine cervical cancers. HPV typing was performed by PCR-RFLP analysis. HPV infection was detected pre-operatively in 29 of 30 patients. Of these, HPV was still present in the 20 patients within two months after the therapy. Topical administration of vidarabine or subsequent 5-FU once a week for four weeks was performed to the post-operative persistent HPV-positive cases. HPV infection was abolished in 1 of 10 (10%) with topical vidarabine, and in 2 of 4 vidarabine-resistant cases (50%) with topical 5-FU. Topical vidarabine or 5-FU treatment is beneficial for HPV-positive cases after local surgical excision.|For more Therapeutic Uses (Complete) data for VIDARABINE (18 total), please visit the HSDB record page.

Vidarabine has been classified as a potential teratogen and should be used with caution during pregnancy (use only for strong clinical indication in absence of suitable alternative).|Hallucinosis has been reported with excessive (as opposed to therapeutic) doses /of Vidarabine/.|Vidarabine should be used only under the close supervision of an ophthalmologist.|Concurrent topical application of vidarabine and a corticosteroid is contraindicated in superficial herpes simplex keratitis. Although concomitant application of vidarabine and a corticosteroid may be of benefit in severe infections, corticosteroids should be used with caution and the patient must be observed closely because of the risk of accelerating the spread of the infection. If a topical corticosteroid is administered concurrently with vidarabine, the possibility of corticosteroid induced adverse ocular effects, including increased intraocular pressure, glaucoma, and cataract formation, must be considered.|For more Drug Warnings (Complete) data for VIDARABINE (10 total), please visit the HSDB record page.

/Vidarabine/ resistant variants due to mutations in viral DNA polymerase can be selected in vitro.

Vira-A is rapidly deaminated to arabinosylhypoxanthine (Ara-Hx), the principal metabolite. ...Because of the low solubility of Vira-A, trace amounts of both Vira-A and Ara-Hx can be detected in the aqueous humor only if there is an epithelial defect in the cornea. If the cornea is normal, only trace amounts of Ara-Hx can be recovered from the aqueous humor. Systemic absorption of Vira-A should not be expected to occur following ocular administration and swallowing lacrimal secretions.|Vidarabine is poorly absorbed following oral, im, or SC administration. Following iv administration of vidarabine, 75-87% of the dose is rapidly deaminated by adenosine deaminase to ara-hypoxanthine. Ara-hypoxanthine also possesses antiviral activity but substantially less than that of vidarabine. Following slow iv administration of vidarabine 10 mg/kg in adults, peak plasma concentrations of the drug range from 0.2-0.4 ug/mL and peak plasma concentrations of ara-hypoxanthine range from 3-6 ug/mL. Plasma concentrations of vidarabine and ara-hypoxanthine are higher and more prolonged in patients with renal impairment.|Vidarabine and ara-hypoxanthine are widely distributed into body tissues and fluids and readily cross the blood-brain barrier. In patients with normal meninges, ara-hypoxanthine concentrations in the CSF are about 33-35% of concurrent plasma concentrations. Vidarabine crosses the placenta in animals. It is not known if vidarabine is distributed into milk. ... Vidarabine is 20-30% bound and ara-hypoxanthine is 0-3% bound to plasma proteins.|Vidarabine and ara-hypoxanthine are excreted mainly by the kidneys. Within 24 hours following iv administration of vidarabine 15 mg/kg in patients with normal renal function, 1-3% of the dose is excreted in urine as vidarabine and 41-53% of the dose is excreted as ara-hypoxanthine. There is no evidence of fecal excretion of the drug or metabolite.

In laboratory animals, Vira-A is rapidly deaminated in the gastrointestinal tract to arabinosylhypoxanthine (Ara-Hx).|Vidarabine is rapidly deaminated, possibly within the cornea, by adenosine deaminase to ara-hypoxanthine. Ara-hypoxanthine also possesses antiviral activity but substantially less than that of vidarabine.

The plasma half-life of vidarabine in adults with normal renal function is 1.5 hr, and the plasma half-life of ara-hypoxanthine is 3.3 hr.

The antiviral mechanism of action has not been established. Vidarabine appears to interfere with the early steps of viral DNA synthesis.|The antiviral mechanism of vidarabine is incompletely understood, but vidarabine is an inhibitor of viral DNA synthesis. Cellular enzymes phosphorylate vidarabine to the triphosphate, which inhibits viral DNA polymerase activity in a manner that is competitive with deoxyadenosine triphosphate. Vidarabine triphosphate is incorporated into both cellular and viral DNA, where it may act as a chain terminator. Vidarabine triphosphate also inhibits ribonucleoside reductase, RNA polyadenylation, and S-adenosylhomocysteine hydrolase (SAHH), an enzyme involved in transmethylation reactions.

SYMPTOMS: Symptoms of exposure to this compound include nausea, vomiting, diarrhea, rash, weakness, thrombophlebitis, hallucinations, psychoses, ataxia, tremor, and dizziness. It can cause gastrointestinal disturbances, confusion, anemia, leukopenia, thrombocytopenia, elevated liver enzymes and bilirubin, corneal changes, and sensitivity changes. In addition, it causes mild itching and irritation of the eyes, and moderate redness of the conjunctiva with temporary punctate keratitis. Anorexia, weight loss, and abnormal EKG have been reported. It causes headache, encephalopathy, decrease in hemoglobin, white blood count, platelet count, and malaise, pruritus, and hematemesis. ACUTE/CHRONIC HAZARDS: This compound may cause lacrimation and irritation. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

/SIGNS AND SYMPTOMS/ Ocular toxicity /including/ punctate keratopathy and hypersensitivity /may occur when using/ topical vidarabine (VIVA-A; 3% ointment) /to treat/ herpes simplex keratitis and conjunctivitis. /From table/|/SIGNS AND SYMPTOMS/ Iv vidarabine causes dose-related GI toxicity, acute neurotoxicities, painful peripheral neuropathy, weakness, hypokalemia, rash, elevated transaminases, anemia, and leukopenia or thrombocytopenia.|/SIGNS AND SYMPTOMS/ Like other ophthalmic ointments, vidarabine may produce a temporary visual haze. Burning, itching, and mild irritation of the affected eye are the most common adverse effects of topical vidarabine therapy; however, lacrimation, foreign body sensation, conjunctival injection, superficial punctate keratitis, pain, photophobia, punctal occlusion, and sensitivity may also occur. Uveitis, stromal edema, secondary glaucoma, trophic defects, corneal vascularization, and hyphema have also been reported, but appear to be disease related.|/GENOTOXICITY/ In vitro, the drug has been shown to cause chromosome breaks and gaps when added to human leukocytes...

Ophthalmic Ointment 3% (equivalent to vidarabine, Vira-A, Parke-Davis anhydrous 2.8%)|Parenteral: Concentrate, for injection, for iv infusion, 200 mg/ml (equivalent to 187.4 mg of anhydrous vidarabine per ml). Vira-A (with benzethonium chloride and phosphate buffers), Parke-Davis|/Vidarabine/ not currently approved for use in the United States

9H-Purin-6-amine, 9-.beta.-D-arabinofuranosyl-: INACTIVE

Analyte: vidarabine; matrix: aqueous parenteral formulation; procedure; ultraviolet spectrometry, polarimetry, and thin-layer chromatography

Analyte: vidarabine; matrix: biological fluid; procedure: reversed-phase high-performance liquid chromatography