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National Skin Centre, Singapore Guidelines for Use of Antivirals for Herpes Zoster Diagnosis of herpes zoster 1). Herpes zoster is diagnosed clinically with the presence of painful grouped vesicles in a dermatomal distribution. Prior to the onset of rash, patients may experience prodromal symptoms of pain, itch or paraesthesia over the involved dermatome. 2). In the history taking, patient should be asked about possibility of underlying immunocompromised states, eg: history of renal transplant on immunosuppressive, chronic dermatosis on long term systemic corticosteroid, recent history of weight loss. 3). During physical examination, besides examining the skin lesions, patient should be examined carefully for the possibility of underlying medical conditions, eg: hepatosplenomegaly, lymphadenopathy. 4). Basic investigations should include full blood count with peripheral blood film examination, urine FEME. Other investigations should be performed if indicated (eg: chest X-ray, malignancy screening). Antiviral medications Antiviral Total cost (approximate) S$ 14.70 Cost per day (approximate) S$ 2.10 S$ 207.93 S$ 29.70 * Valtrex (valaciclovir) Recommended treatment 800 mg, 5 times per day for 7 days * For children, 20mg/kg (not to exceed 800mg), QDS 800 mg, 5 times per day for 7 days 1 gm, 3 times per day for 7 days S$ 193.8 S$ 27 # Famvir (famciclovir) 250 mg, 3 times per day for 7 days S$ 387.60 S$ 55.40 * Generic acycovlir # Zovirax Note: * Available in NSC Page 1 # Retail price from private pharmacies. Use of antivirals 1) Aims of treatment: a) b) c) 2) Shorten duration of acute illness. Reduce the severity of acute illness. Reduce the risk of herpes associated pain, especially chronic pain. Available data on clinical outcomes of herpes zoster for patients treated with antivirals: Patients treated with valaciclovir heals significantly faster than patients treated with acyclovir and patients not treated with antiviral. Patients treated with acyclovir may form scab faster than untreated patients, but the duration taken for complete healing was not significantly different. The incidence of zoster associated pain decreases with time in all patients. However, older patients have higher incidence of zoster associated pain at all time intervals from onset of rash compared to the younger patients. The incidence of zoster associated pain at 1 month for patients older than 50 years-old was 62%, compared to 29% for those younger than 30, while the corresponding incidence by 6 months was 20% and 7% respectively. Significantly fewer patients treated with valaciclovir have zoster associated pain at various time intervals from onset of zoster compared to patients treated with acyclovir and untreated patients. The corresponding incidences of zoster associated pain at 1, 3, 6 months after onset of rash for patients treated with valaciclovir (23.5%, 5.9%, 0%) were significantly lower than those treated with acyclovir (48.3%, 24.1%, 17.2%) and untreated patients (49.4%, 27.4%, 17.7%). The difference between patients treated with acyclovir and untreated patients was not significant. 3) Indications for use of antivirals: a) Patients at high risk of disseminated herpes, eg: immunocompromised patients ( patients on chemotherapy, patients on long term corticosteroids, transplant patients on immunosuppressive ) b) Patients at high risk of prolonged zoster associated pain, eg: patients older than 50-year-old. Page 2 4) Timing of antivirals: Antivirals should be used as early in the course of disease as possible. The recommended cut-off time of 72 hours may not be applicable to all patients, especially immunocompromised patients. These patients should be given antivirals as long as the disease is still active. 5) Choice of antivirals: a) Acyclovir should be the antiviral of choice unless the use of antiviral is specifically aim to reduce the incidence of zoster associated pain. b) Valtrex (valaciclovir) is thus indicated for: (i) 6) Patients older than 50. Adjunctive treatments: (i) Pain killers. Patients should be prescribed pain killer as pain is present in more than 90% of the patients during the acute illness and it is also often regarded as having the greatest impact on patients’ life, eg: Naproxen sodium 275mg bd. (ii) Sleeping pills. Many patients have insomnia during the illness and will benefit from short term use of sleeping pills, eg: Dormicum 7.5 mg ON, Valium 5mg ON. (iii). Skin care. During the acute blistering phase of the disease, patients treated with saline compress, the blisters may be pricked and covered with tetracyclince ointment and melolin dressing. Emollients, eg: aqueous cream, should be applied once crusting takes place. (iv). Ophthalmic involvement. In herpes zoster ophthalmicus, the ophthalmic division of the fifth cranial nerve is involved. If the external division of the nasociliary branch is affected, with vesicles on the side and tip of the nose (Hutchinson’s sign), the eyeball is involved in 76% of the time, as compared with 34% when it si not involved. Vesicles on the lid margin are virtually always associated with ocular involvement. Patients with ophthalmic zoster should be seen by an ophthalmologist. Page 3 (V). Management of postherpetic neuralgia (Zoster-associated pain) a). Topical treatment (i). First line Capsaicin cream 0.025%, applied every few hours. Capsaicin itself may cause burning sensation. (ii). Second line Local anesthetis (eg: 10% lidocaine gel, 5% lidocaine-prilocaine, lidocaine patches ) may acutely reduce pain. Topical aspirin in ether or chloroform (eg: 750 mg of acetylsalicylic in 20 to30 ml of liquid). b). Systemic treatment (i). First line Simple analgesics (eg: paracetamol, NSAIDS) Tricyclic antidepressants (eg: amitriptyline and desipramine, at 25 to 75 mg in a single nightly dose). (ii). Second and third line Anticonvulsants, such as carbamazepine, valproate. Neuroleptics, such as chlorprothixene, phenothiazines. H2 blockers, such as cimetidine. Gabapentin, may be added in escalating doses up to 3200 mg/ day. Opiate analgesics. Patients with difficult to manage herpes associated pain should be referred to the “Pain Clinic” for expert management. Annex 1 Clinical data on antiviral usage for herpes zoster a) Duration taken for healing of rash: Duration for scabbing to occur (days) Duration for complete healing of rash (days) Page 4 No treatment 11.1 Acyclovir 8.2* Valaciclo vir 6.8* 20.8 16.4# 13.4* # = statistically not significant * = statistically significant b) Herpes associated pain at 1, 3, 6 and after six months for different age groups if without treatment: At 1 month * At 3 months * At 6 months More than 6 months <30 years 29% 11% 7% 7% 30 - 50 years 46% 24% 18% 16% > 50 years 62% 39% 23% 20% * = statistically significant among different age groups c) Herpes associated pain at 1, 3, 6 and after 6 months for different treatment groups: At 1 month At 3 months At 6 months More than 6 months No treatment 49.4% 27.4% 17.7% 15.9% Acyclovir Valaciclovir 48.3% 24.1% 17.2% 13.8% 23.5%* 5.9%* 0%* 5.9% * = statistically significant compared to no treatment group Page 5 Herpes Zoster Immunocompetent Paediatric ( < 12 ) Adults ( < 50 ) ( 13 - 50 ) > 72 hrs Immuno-compromised Generic acyclovir until lesions healed ( > 50 ) < 72 hrs > 72 hrs < 72 hrs > 72 hrs - No antiviral - skin care, etc - No anti-viral -skin care -analgesic - antibiotic - sedation Generic acyclovir - No anti-viral -skin care -analgesic - antibiotic - sedation Generic acyclovir Page 6 < 72 hrs Valtrex