药品英文名
Vidarabine
药品别名
阿糖腺苷、Ara-A、Vidarabinum、Vira-A
药物剂型
1.注射剂：200mg(1ml)(相当于187.4mg无水品)，内含杀菌剂氯化苄甲乙氧胺和磷酸盐缓冲剂；
2.注射剂(混悬液)：0.2g(1ml)，1g(5ml)；
3.眼膏：3%(相当于无水品2.8%)。
药理作用
本药为嘌呤核苷，系抗病毒药，其抗病毒的确切机制尚未完全阐明，主要与抑制病毒的复制有关。本药及其代谢物通过抑制病毒的DNA多聚酶，从而阻断病毒DNA的合成，而药物本身仅极少量渗入病毒的DNA分子中。本药的抗病毒作用部分取决于宿主的免疫功能。本药无免疫抑制作用。本药对单纯疱疹病毒Ⅰ和Ⅱ型、带状疱疹病毒、水痘病毒、巨细胞病毒、乙型肝炎病毒均具抗病毒活性，但对天花病毒、腺病毒、其他DNA或RNA病毒、细菌和真菌均无作用。本品的单磷酸酯有抑制乙肝病毒复制的作用。
药动学
本药口服、肌注或皮下注射吸收均差。静脉给药后，75%～87%的药物在血液和细胞内迅速被腺苷脱氨酶脱氨基，生成阿拉伯糖次黄嘌呤，并迅速分布进入一些组织中。阿拉伯糖次黄嘌呤的抗病毒的活性仅为阿糖腺苷的1/30～1/50，但能增加阿糖腺苷的抗病毒活性。
本药缓慢静脉滴注10mg/kg后30min，阿拉伯糖次黄嘌呤的血药浓度峰值为3～6μg/ml，阿糖腺苷则为0.2～0.4μg/ml。停药后血浆药物浓度迅速下降，平均15～20min后血中即测不出。
本药在肾、肝、脾浓度最高，脑、骨骼肌中浓度较低；阿拉伯糖次黄嘌呤可透过脑膜，脑脊液与血浆中的浓度比为1:3。本药主要自肾脏排出，24h以次黄嘌呤核苷的形式排出给药量的41%～53%(原药仅1%～3%)。
肾功能不全者，阿拉伯糖次黄嘌呤可在体内蓄积，其血药浓度可为正常人的几倍。阿拉伯糖次黄嘌呤的平均半衰期为3.3h。局部用药时本药很少进入全身，但角膜上皮细胞有损害时房水中可测出少量本药及其代谢物；角膜完整者，房水中仅有少量代谢物存在。
适应证
1.用于单纯疱疹性脑炎、新生儿单纯疱疹病毒感染(如皮肤黏膜感染、局限性中枢神经系统感染和播散性单纯疱疹感染)和带状疱疹。
2.用于免疫功能缺陷者的水痘病毒感染、带状疱疹、婴儿先天性巨细胞和免疫缺陷者巨细胞病毒感染。
3.本药眼膏用于单纯疱疹病毒性角膜炎，偶用于牛痘病毒性角膜炎；也可用于经碘苷治疗无效或对碘苷过敏的浅表性疱疹病毒性角膜炎。
禁忌证
1.对本药或含本药药物过敏者禁用；
2.孕妇及哺乳妇女忌用。
注意事项
1.慎用：有肝、肾功能损害者慎用。
2.用药期间可出现氨基转移酶升高、血胆红素升高、血红蛋白减少、红细胞比容下降、血细胞减少、血小板减少、网织红细胞减少等实验室指标异常。
3.用药期间须定期监测血象及肝、肾功能。
4.本药静脉滴注时，大量液体伴随本药进入体内，应注意水、电解质平衡。
5.本品不可静脉推注或快速滴注。
6.配制好的药液不可冷藏以免析出结晶。
不良反应
本药的毒性反应与剂量成正比。
1.消化系统：静脉给药剂量超过20mg/kg时，大多会出现消化道的不良反应，常见恶心、呕吐、腹痛、腹泻、便秘、食欲减退和体重减轻，常在用药第2、3天开始，继续给药，反应可在1～4天内减轻。尚可出现暂时性氨基转移酶升高和血总胆红素升高。也有发生呕血的报道
2.中枢神经系统：偶见震颤、眩晕、幻觉、共济失调、癫痫发作、精神症状和意识模糊等，其发生与剂量有关，通常停药后可自行消退。也有出现头痛和脑病的报道，后者常难以与原发病相识别，多发生于肝、肾功能不全者。另有霍奇金病患者使用本药发生暂时性运动性失语症的报道。
3.血液系统：可出现血红蛋白减少、血细胞比容下降、白细胞减少、血小板减少、网织红细胞减少等，大多不必停药，且在疗程结束后3～5天恢复。静脉给药每天剂量超过20mg/kg时，可引起骨髓抑制，偶有骨髓内巨幼红细胞增多。
4.内分泌/代谢：有报道本药可引起抗利尿激素异常分泌综合征和血钠过低。
5.皮肤：可出现皮疹、瘙痒等。
6.局部反应：
(1)静脉滴注部位可出现疼痛和血栓性静脉炎，大多在停药后消退；
(2)局部眼科用药时，常引起暂时性烧灼、痒等轻度刺激感，也可出现流泪、异物感、结膜充血、表浅点状角膜炎、疼痛、怕光等反应。
7.致突变与致癌性：动物实验显示本药可致突变，致肝、肾、甲状腺、小肠等肿瘤，体外测定也显示本药可致人体白细胞染色体断裂和畸形，但其意义尚未阐明。
8.致畸性：动物实验表明本药有致畸作用。
9.其他：可出现发热、全身乏力。
用法用量
1.成人：
(1)静脉滴注：
①单纯疱疹病毒性脑炎：每天15mg/kg，作连续缓慢静脉滴注，以超过12h为宜，疗程为10天；
②带状疱疹：每天10mg/kg，疗程为5天，用法同上；
③免疫缺陷者水痘感染：每天10mg/kg，疗程为5～7天；
④慢性乙肝：每天5～10mg/kg，疗程为49～81天。
(2)经眼给药：用于单纯疱疹性角膜炎的治疗时，可用本药3%的眼膏，每次向结膜囊内涂1cm长眼膏，每3小时1次，每天5次，10～14天为1个疗程。严重病例的疗程可更长。用药至角膜上皮形成后，还应继续用药5～7天，每天2次，以防复发。
(3)肾功能不全时剂量：肾功能不全者应根据肾功能损害程度调整剂量。肾小球滤过率低于每分钟10ml者可用常用剂量的75%。
2.儿童静脉滴注：
(1)单纯疱疹病毒性脑炎：
①用法与用量同成人；
②新生儿：每天15mg/kg，疗程10～14天。
(2)带状疱疹：用法与用量同成人。
药物相应作用
1.与腺苷脱氨酶抑制剂合用时，本药的抗病毒效力可提高20～50倍。
2.本药与氨茶碱联用时可使氨茶碱的血药浓度升高。
3.本药与喷司他丁合用时，虽可提高本药的疗效，但也使两者不良反应的发生率增加。
4.别嘌醇和茶碱能抑制黄嘌呤氧化酶，与本药合用时可使阿拉伯糖次黄嘌呤的消除减慢而蓄积，可致较严重的神经系统毒性反应。因而使用本药时上述药物应慎用。
专家点评
本品为一嘌呤核苷类抗病毒药。对疱疹病毒、水痘、带状疱疹病毒、腺病毒、伪狂犬病毒E-B病毒、巨细胞病毒、Rous肉瘤病毒和Gross白血病病毒等病毒均有抑制作用。此外，对少数RNA病毒也有抑制作用。临床主要用于防治单纯疱疹病毒性脑炎、新生儿单纯疱疹感染、带状疱疹、水痘，也用于免疫功能缺陷者和水痘病毒感染、婴儿先天性巨细胞病毒感染和免疫缺陷者巨细胞病毒感染。局部用于单纯性疱疹病毒角膜炎、虹膜炎，偶可用于牛痘病毒性角膜炎

Drug Description

VIRA-A
(vidarabine monohydrate) Ointment

VIRA-A is the trade name for vidarabine (also known as adenine arabinoside and Ara-A), an antiviral drug for the topical treatment of epithelial keratitis caused by Herpes simplex virus. The chemical name is 9H-Purin-6-amine, 9-β-D-arabinofuranosyl-, monohydrate.

Each gram of the ophthalmic ointment contains 30 mg of vidarabine monohydrate equivalent to 28.11 mg of vidarabine in a sterile, inert, petrolatum base.

Indications & Dosage

VIRA-A (vidarabine) Ophthalmic Ointment, 3%, is indicated for the treatment of acute keratoconjunctivitisand recurrent epithelial keratitis due to Herpes simplex virus types l and 2. The clinical diagnosis of keratitis caused by Herpes simplex virus is usually established by the presence of typical dendritic or geographic lesions on slit-lamp examination. It is also effective in superficial keratitis caused by Herpes simplex virus which has not responded to topical idoxuridine or when toxic or hypersensitivity reactions due to idoxuridine have occurred. The effectiveness of VIRA-A (vidarabine) Ophthalmic Ointment, 3%, against stromal keratitis and uveitis due to Herpes simplex virus has not been established.

Administer approximately one-half inch of VIRA-A (vidarabine) Ophthalmic Ointment, 3%, into the lower conjunctival sac five times daily at three-hour intervals.

If there are no signs of improvement after 7 days, or complete re-epithelialization has not occurred by 21 days, other forms of therapy should be considered. Some severe cases may require longer treatment.

Too frequent administration should be avoided.

After re-epithelialization has occurred, treatment for an additional 7 days at a reduced dosage (such as twice daily) is recommended in order to prevent recurrence.

The following topical antibiotics: gentamicin, erythromycin, chloramphenicol; or topical steroids: prednisolone or dexamethasone have been administered concurrently with VIRA-A (vidarabine) Ophthalmic Ointment, 3%.

NDC 61570-367-71

VIRA-A (vidarabine) Ophthalmic Ointment, 3%, is supplied sterile in ophthalmic ointment tubes of 3.5 g. The base is a 60:40 mixture of solid and liquid petrolatum.

Store at room temperature 15°–30°C (59°F–86°F).

Distributed by: Monarch Pharmaceuticals, Inc., Bristol, TN 37620. Manufactured by: Parkedale Pharmaceuticals, Inc., Rochester, MI 48307.

Side Effects & Drug Interactions

Lacrimation, foreign body sensation, conjunctival injection, burning, irritation, superficial punctatekeratitis, pain, photophobia, punctal occlusion, and sensitivity have been reported with VIRA-A (vidarabine) Ophthalmic Ointment, 3%. The following have also been reported but appear disease-related: uveitis, stromal edema, secondary glaucoma, trophic defects, corneal vascularization, and hyphema.

No information provided.

Warnings & Precautions

Normally, corticosteroids alone are contraindicated in Herpes simplex virus infections of the eye. If VIRA-A (vidarabine) Ophthalmic Ointment, 3%, is administered concurrently with topical corticosteroid therapy, corticosteroid-induced ocular side effects must be considered.

These include corticosteroid-induced glaucoma or cataract formation and progression of a bacterial or viral infection.

VIRA-A (vidarabine) is not effective against RNA virus or adenoviral ocular infections. It is also not effective against bacterial, fungal, or chlamydial infections of the cornea or nonviral trophic ulcers.

Although viral resistance to VIRA-A (vidarabine) has not been observed, this possibility may exist.

The diagnosis of keratoconjunctivitis due to Herpes simplex virus should be established clinically prior to prescribing VIRA-A (vidarabine) Ophthalmic Ointment, 3%.

Patients should be forewarned that VIRA-A (vidarabine) Ophthalmic Ointment, 3%, like any ophthalmic ointment, may produce a temporary visual haze.

Chronic parenteral (IM) studies of vidarabine have been conducted in mice and rats.

In the mouse study, there was a statistically significant increase in liver tumor incidence among the vidarabine-treated females. In the same study some vidarabine-treated male mice developed kidneyneoplasia. No renal tumors were found in the vehicle-treated control mice or the vidarabine-treated female mice.

In the rat study, intestinal, testicular, and thyroid neoplasia occurred with greater frequency among the vidarabine-treated animals than in the vehicle-treated controls. The increases in thyroid adenomaincidence in the high-dose (50 mg/kg) males and the low-dose (30 mg/kg) females were statistically significant.

Hepatic megalocytosis, associated with vidarabine treatment, has been found in short and long-term rodent (rat and mouse) studies. It is not clear whether or not this represents a preneoplastic change.

The recommended frequency and duration of administration should not be exceeded (see DOSAGE AND ADMINISTRATION).

Results of in vitro experiments indicate that vidarabine can be incorporated into mammalian DNA and can induce mutation in mammalian cells (mouse L5178Y cell line). Thus far, in vivo studies have not been as conclusive, but there is some evidence (dominant lethal assay in mice) that vidarabine may be capable of producing mutagenic effects in male germ cells.

It has also been reported that vidarabine causes chromosome breaks and gaps when added to human leukocytes in vitro. While the significance of these effects in terms of mutagenicity is not fully understood, there is a well-known correlation between the ability of various agents to produce such effects and their ability to produce heritable genetic damage.

VIRA-A (vidarabine) parenterally is teratogenic in rats and rabbits. Ten percent VIRA-A (vidarabine) ointment applied to 10% of the body surface during organogenesis induced fetal abnormalities in rabbits. When 10% VIRA-A (vidarabine) ointment was applied to 2% to 3% of the body surface of rabbits, no fetal abnormalities were found. This dose greatly exceeds the total recommended ophthalmic dose in humans. The possibility of embryonic or fetal damage in pregnant women receiving VIRA-A (vidarabine) Ophthalmic Ointment, 3%, is remote. The topical ophthalmic dose is small, and the drug relatively insoluble. Its ocular penetration is very low. However, a safe dose for a human embryo or fetus has not been established. There are no adequate and well-controlled studies in pregnant women. VIRA-A (vidarabine) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether VIRA-A (vidarabine) is secreted in human milk. Because many drugs are excreted in human milk and because of the potential for tumorigenicity shown for VIRA-A (vidarabine) in animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. However, breast milk excretion is unlikely because VIRA-A (vidarabine) is rapidly deaminated in the gastrointestinal tract.

The safety and effectiveness in pediatric patients below the age of 2 years have not been established.

Overdosage & Contraindications

Acute massive overdosage by oral ingestion of the ophthalmic ointment has not occurred. However, the rapid deamination to arabinosylhypoxanthine should preclude any difficulty. The oral LD50 for vidarabine is greater than 5020 mg/kg in mice and rats. No untoward effects should result from ingestion of the entire contents of the tube.

Overdosage by ocular instillation is unlikely because any excess should be quickly expelled from theconjunctival sac.

VIRA-A (vidarabine) Ophthalmic Ointment, 3%, is contraindicated in patients who develop hypersensitivity reactions to it.

Clinical Pharmacology

VIRA-A (vidarabine) is rapidly deaminated to arabinosylhypoxanthine (Ara-Hx), the principal metabolite. Ara-Hx also possesses in vitro antiviral activity but this activity is less than that of VIRA-A (vidarabine) . Because of the low solubility of VIRA-A (vidarabine) , trace amounts of both VIRA-A (vidarabine) 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 (vidarabine) should not be expected to occur following ocularadministration and swallowing lacrimal secretions. In laboratory animals, VIRA-A (vidarabine) is rapidly deaminated in the gastrointestinal tract to Ara-Hx.

In contrast to topical idoxuridine, VIRA-A (vidarabine) demonstrated less cellular toxicity in the regenerating corneal epithelium of the rabbit.

In controlled and uncontrolled clinical trials, an average of seven and nine days of continuous VIRA-A (vidarabine) Ophthalmic Ointment, 3%, therapy was required to achieve corneal re-epithelialization. In the controlled trials, 70 of 81 subjects (86%) re-epithelialized at the end of three weeks of therapy. In the uncontrolled trials, 101 of 142 subjects (71%) re-epithelialized at the end of three weeks.

Seventy-five percent of the subjects in these uncontrolled trials had either not healed previously or had developed hypersensitivity to topical idoxuridine therapy.

Vidarabine is a purine nucleoside obtained from fermentation cultures of Streptomyces antibioticus. The antiviral mechanism of action has not been established. Vidarabine appears to interfere with the early steps of viral DNA synthesis.

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.

No universal, standardized, quantitative in vitro procedures have as yet been developed to estimate the susceptibility of viruses to antiviral agents.