Aciclovir topical

Aciclovir is phosphorylated preferentially by herpes simplex virus-coded thymidine kinase and following further phosphorylation aciclovir triphosphate interferes with herpes virus DNA polymerase and viral DNA replication. Aciclovir topical cream is indicated in the management of initial genital herpes and in limited non-life threatening mucocutaneous herpes simplex virus infections in immunocompromised patients. 

Aciclovir is an antiviral indicated in the treatment and prophylaxis of cold sores. It is available for systemic administration (tablets) or topical use (cream, eye ointment). In the management of cold sores, the cream is applied every 4 hours and continued for 5 days. Its use should be started as soon as symptoms (tingling sensation) begin. 

Vidarabine (adenine arabinoside, ara-A) is phos-phorylated in the cell to the triphosphate derivative which blocks DNA synthesis by inhibiting DNA polymerase. It is indicated for infections with herpes simplex virus and varicella-zoster however its use has to a large extend been surpassed by aciclovir. It is administered topically or intravenously. It is inactivated rapidly by adenosine deaminase which for systemic use necessitates constant infusion of the drug. Vidarabine is the least toxic of the purine analogues. Nausea and vomiting are the most frequent adverse effects and neurotoxicity may occur. 

Topical aciclovir has limited effectivity in the treatment of recurrent herpes genitalis or herpes febrilis infections in non-immunocompromised patients, although topical aciclovir may cause some reduction in the duration of viral shedding. Topical aciclovir has no role in the treatment of herpes zoster. 

Penciclovir is an other nucleoside analogue with a similar mechanism of action as aciclovir. Also with penciclovir the efficacy of topical use is marginal at best. 

Foscarnet is an inorganic pyrophosphate analogue which causes selective inhibition of viral DNA polymerase and reverse transcriptase. Topical foscarnet cream has appeared to be a safe and effective treatment for aciclovir-unresponsive mucocutaneous herpes simplex virus infection in AIDS patients. 

Lin L, Chen XS, Cui PG, et al. Topical application of penciclovir cream for the treatment of herpes simplex facialis/labialis a randomized, double-blind, multicentre, aciclovir-controlled trial. J Dermatolog Treat. 2002 13 67-72. 

Phosphorylated aciclovir inhibits DNA polymerase and so prevents viral DNA being formed. It effectively treats susceptible herpes viruses if started early in the course of infection, but it does not eradicate persistent infection. Taken orally about 20% is absorbed from the gut, but this is sufficient for the systemic treatment of some infections. It distributes widely in the body the concentration in CSF is approximately half that of plasma, and the brain concentration may be even less. These differences are taken into account in dosing for viral encephalitis (for which aciclovir must be given i.v.). The drug is excreted in the urine (t, 3 h). For oral and topical use the drug is given x 5/d. 

Idoxuridine was the first widely used antivirus drug. It is superseded by aciclovir and is variably effective topically for ocular and cutaneous herpes simplex with few adverse reactions. 

Virus infections. Topical antivirals aciclovir (acyclovir). (see p. 257). Aciclovir is used systemically for the potentially severe infections, e.g. eczema herpeticum. 

Aciclovir is used topically or systemicaUy, orally or intravenously. Its therapeutic potential is most impressive in active parenchymal or systemic HSV infections. The latency stage of the viral infection is not affected. Since the blood-brain barrier is well penetrated, aciclovir is the treatment of choice for HSV encephalitis. 

Neurotoxicity possibly secondary to the topical use of aciclovir has also been described (10). 

A 59-year-old woman on hemodialysis was treated with oral aciclovir 200 mg/day for ophthalmic Herpes zoster. After a few days, an ophthalmic aciclovir cream was started (one application every 6 hours) because of ipsi-lateral Herpes keratitis. After 1 week of combined oral and topical treatment, she became confused, with dysarthria and audiovisual hallucinations. Aciclovir was withdrawn and hemodialysis was initiated. Complete resolution of symptoms was achieved after three hemodialysis sessions in 3 days. Aciclovir plasma concentrations before hemodialysis were high (45 pmol/l) and fell rapidly during hemodialysis. 

There is no conclusive evidence for the contribution of the topically administered aciclovir to the high plasma concentrations and subsequent neurotoxicity in this case. However, the authors argued that the existence of high aciclovir plasma concentrations, in spite of careful adjustment of the oral dosage, pointed to significant topical absorption of the drug, especially since the absorption of aciclovir through the skin and mucous membranes may be unpredictable. Coma has been attributed to oral aciclovir (11). 

A 16-year-old girl with an 11-year history of frequent cold sores developed an erythematous rash and severe contact dermatitis during oral and topical aciclovir therapy (24). Patch tests showed contact sensitization to aciclovir and to the related compound ganciclovir. 

In a 44-year-old woman who used topical aciclovir for genital herpes, aciclovir contact allergy was associated with a systemic contact allergic reaction with an erythematous vesiculobullous eruption in the labial and perioral skin and a rash on the upper trunk and extremities (25). Patch tests were positive to aciclovir, valaciclovir, and ganciclovir, but not to famciclovir. 

A 72-year-old woman was treated for thoracic Herpes zoster with oral aciclovir and topical benzocaine 20% ointment. She subsequently developed painful pruritic erythematous dermatitis in the area of the lesions, spreading to her arm. The dermatitis was initially misdiagnosed as aciclovir resistance, but on patch testing she had a positive reaction to benzocaine. 

Aciclovir is a guanosine analog that is converted to the active trisphosphate form by a viral-encoded thymidine kinase which is present only in infected cells. Aciclovir trisphosphate inhibits DNA polymerase but has much greater affinity for the viral enzyme than for the host cell enzyme. As a result, aciclovir is relatively non-toxic to uninfected host cells. Its efficacy in putative viral keratitis in the horse is unpredictable but, in general, it is effective in type 2 but not type 1 disease. It may be commercially available as a 3% ointment for topical ophthalmic use and should be applied every 3-4 h. 

Evidence of the effectiveness of topical aciclovir has not been convincing, but it may shorten attacks by a day or two if use is begun early enough. 

Topical aciclovir is not well tolerated by patients after a deep peel because of the burning sensation it triggers. If pain is very local, EMLA cream can be used cautiously, as it is absorbed more readily through skin that has no stratum corneum and is damaged by herpes. Local corticosteroids should not be used. 

This appears to be the first and only report of this interaction, but it would now be prudent to monitor for symptoms of lithium toxicity (see Lithium , (p.llll)) and consider monitoring lithium levels if high-dose intravenous aciclovir is given to any patient. The report recommends measuring lithium levels every second or third day. Oral aciclovir is predicted not to interact because of its low bioavailability, and no interaction would be expected with topical aciclovir as the plasma levels achieved by this route are minimal. 

A 40-year-old man developed acute retinal necrosis and was given intravenous aciclovir 15 mg/kg every 8 hours, in addition to intra-vitreal foscarnet 2.4 mg and topical moxifloxa-cin, prednisolone, and cyclopentolate [16 -The baseline serum creatinine was 53 pmol/l, which increased to 80 pmol/1 by day 2 (when oral prednisolone, 60 mg/day, was also started) and 265 p.mol/1 by day 3. Apart from the aciclovir, no other nephrotoxic agents were administered. Renal tract ultrasound was normal. Aciclovir was withheld after three doses and ganciclovir was started. His renal function normalized within 7 days. 

Skin In a 20-year-old woman with acute allergic contact dermatitis of the lips and perioral skin after the application of a cream containing aciclovir, scratch-patch tests (patch tests after scarification of the epidermis) with aciclovir 1%, 5% petrolatum, and the other components of the cream (Cycloviran ) produced strong positive reactions to aciclovir and petrolatum only conventional patch tests had been negative or doubtful [5 ]. Topical 1% fos-camet cream did not produce a reaction. 

Local inflammatory reactions, burning and tingling are reported with topical aciclovir. In 134 subjects in a phase III study to assess the safety of the combination of 5% aciclovir and 1% hydrocortisone cream in the treatment of recurrent herpes simplex labialis in immunocompetent adolescents, one 14-year-old girl developed a localised... 

A prospective randomised study compared a novel barrier gel (CS20) with topical aciclovir. There were five cases of burning or tingling on product application in the 35 patients randomised to aciclovir [44 ]-... 

Khemis A, Duteil L, Coudert AG, TiUet Y, Dereure O, Ortonne JP. Evaluation of the efficacy and safety of a CS20 protective barrier gel containing OGT compared with topical aciclovir and placebo on functional and objective symptoms of labial herpes recurrence a randomized clinical trial. J Eur Acad Dermatol Venereol 2012 26(10) 1240-6. 

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