Medication Summary
The goals of therapy in herpes zoster infection are to (1) shorten the clinical course, (2) provide analgesia, (3) prevent complications, and (4) decrease the incidence of postherpetic neuralgia. Meta-analyses and randomized controlled trials suggest that the oral antiviral agents acyclovir, famciclovir, and valacyclovir, started within 72 hours of the onset of rash, reduce the severity and duration of acute pain, as well as the incidence of postherpetic neuralgia.
Antivirals
Class Summary
The goals of antiviral therapy are to decrease pain, inhibit viral replication and shedding, promote healing of skin lesions, and prevent or reduce the severity of postherpetic neuralgia. Acyclovir may also decrease the incidence of postherpetic neuralgia. Famciclovir and valacyclovir (antiviral agents with properties similar to those of acyclovir) offer more convenient dosing regimens than acyclovir. They also have been less studied and are more expensive.
Acyclovir (Zovirax)
Acyclovir is a guanine derivative that prevents varicella-zoster virus (VZV) replication through inhibition of the viral DNA polymerase. It reduces the duration of symptomatic lesions.
Famciclovir (Famvir)
After ingestion, famciclovir is rapidly biotransformed into the active compound penciclovir and phosphorylated by viral thymidine kinase. By competition with deoxyguanosine triphosphate, penciclovir triphosphate inhibits viral polymerase. Adjust the dose in patients with renal insufficiency or hepatic disease.
Valacyclovir (Valtrex)
Valacyclovir is a prodrug that is rapidly converted to acyclovir before exerting its antiviral activity.
Corticosteroids
Class Summary
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli. The use of oral or epidural corticosteroids in conjunction with antiviral therapy has been found to be beneficial in treating moderate to severe acute zoster, but to have no effect on the development or duration of postherpetic neuralgia.[28, 29, 36]
Intrathecal administration of corticosteroids has been shown to produce a significant reduction in postherpetic neuralgia.[50] However, as these results have not received independent confirmation, and there are significant safety concerns with administration of intrathecal steroids, this treatment modality is not recommended.
Prednisone (Sterapred)
The addition of oral corticosteroids has been evaluated in zoster patients treated with acyclovir in 2 controlled studies. Steroids were found to accelerate the resolution of acute neuritis and provide a clear improvement in quality-of-life measures in comparison to those patients treated with antivirals alone. The use of oral steroids had no effect on the development or duration of postherpetic neuralgia. Oral steroids have not been studied with valacyclovir or famciclovir, so the benefit is unknown.
Analgesics
Class Summary
Pain control is essential to quality patient care. Analgesics ensure patient comfort, promote pulmonary toilet, and enable physical therapy regimens. Most oral narcotic analgesics have sedating properties that are beneficial for patients who have skin lesions. Topical analgesics that contain capsaicin have been shown to be effective for neuropathic pain associated with postherpetic neuralgia.
Oxycodone (OxyContin, Roxicodone)
Oxycodone is a narcotic analgesic that is indicated for the relief of moderate to severe pain. Patients with herpes zoster usually experience pain. Antiviral and steroid therapies provide relatively minor relief of pain, and narcotic analgesics are often needed.
Acetaminophen (Tylenol, Aspirin-Free Anacin)
This is the drug of choice for the treatment of pain in patients who (1) have documented hypersensitivity to aspirin or NSAIDs, (2) have upper GI disease, or (3) are taking oral anticoagulants. Acetaminophen reduces fever by direct action on hypothalamic heat-regulating centers, which increases dissipation of body heat via vasodilation and sweating.
Ibuprofen (Motrin, Advil)
Ibuprofen is the drug of choice for the treatment of mild to moderately severe pain, if no contraindications exist. It inhibits inflammatory reactions and pain, probably by decreasing the activity of the enzyme cyclooxygenase, which, in turn, inhibits prostaglandin synthesis. Ibuprofen is one of the few NSAIDs that are indicated for fever reduction.
Naproxen (Naprosyn, Naprelan, Anaprox)
Naproxen is commonly used for the relief of mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis.
Topical Analgesics
Class Summary
Topical analgesics decrease the pain associated with postherpetic neuralgia.
Capsaicin (Capzasin-P, Zostrix)
Capsaicin is derived from plants of the Solanaceae family. It is a transient receptor potential vanilloid-1 (TRPV1) agonist indicated for neuropathic pain associated with postherpetic neuralgia. TRPV1 is an ion channel–receptor complex expressed on nociceptive skin nerve fibers. Topical capsaicin causes initial TRPV1 stimulation that may cause pain, followed by pain relief via a reduction in TRPV1-expressing nociceptive nerve endings. Neuropathic pain may gradually recur over several months; this recurrence is thought to be caused by TRPV1 nerve fiber reinnervation of the treated area.
Capsaicin transdermal patch (Qutenza)
This is a transient receptor potential vanilloid-1 (TRPV1) agonist indicated for neuropathic pain associated with postherpetic neuralgia. TRPV1 is an ion channel–receptor complex expressed on nociceptive skin nerve fibers. Topical capsaicin causes initial TRPV1 stimulation that may cause pain, followed by pain relief via a reduction in TRPV1-expressing nociceptive nerve endings. Neuropathic pain may gradually recur over several months; this recurrence is thought to be caused by TRPV1 nerve fiber reinnervation of the treated area.
Vaccines
Class Summary
These agents elicit active immunization to increase resistance to infection. Vaccines consist of attenuated microorganisms or cellular components, which act as antigens. Administration stimulates antibody production with specific protective properties.
Varicella zoster vaccine (Zostavax)
This is a lyophilized preparation of the Oka/Merck strain of live, attenuated varicella-zoster virus (VZV). It has been shown to boost immunity against herpes zoster virus (shingles) in older patients. It reduces the occurrence of shingles in individuals older than 60 years by about 50%. For individuals aged 60-69 years, it reduces the occurrence by 64%. In the ZEST trial, the vaccine significantly reduced the risk by 70% in subjects aged 50-59 years. It also slightly reduces pain compared with no vaccination in those who develop shingles. It is indicated for the prevention of herpes zoster in patients who have no contraindications.
Anticonvulsants
Class Summary
Most often used as antiepileptics, certain anticonvulsants are also effective for treating neuropathic pain.
Gabapentin (Neurontin)
Gabapentin is a membrane stabilizer, a structural analogue of the inhibitory neurotransmitter gamma-amino butyric acid (GABA), which paradoxically is thought not to exert effect on GABA receptors. Gabapentin appears to exert action via the alpha2delta1 and alpha2delta2 auxiliary subunits of voltage-gated calcium channels. It is used to manage pain and provide sedation in neuropathic pain. Gabapentin is primarily used for the treatment of postherpetic neuralgia. It has also been used to treatment the pain of acute zoster.
Pregabalin (Lyrica)
Pregabalin is a structural derivative of GABA. It binds with high affinity to the alpha2-delta site (a calcium channel subunit). In vitro, it reduces calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. It is FDA approved for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures.
Tricyclic antidepressants
Class Summary
Tricyclic antidepressants have been shown to have a role in the treatment of postherpetic neuralgia.
Amitriptyline
This agent blocks the reuptake of norepinephrine and serotonin. It decreases pain by inhibiting spinal neurons involved in pain perception.
Desipramine (Norpramin)
Desipramine is a tricyclic antidepressant that has the least adverse effects amongst the first generation tricyclic antidepressants. These agents have been found to be effective in providing relief of postherpetic neuralgia.
Pasqualucci A, Pasqualucci V, Galla F, et al. Prevention of post-herpetic neuralgia: acyclovir and prednisolone versus epidural local anesthetic and methylprednisolone. Acta Anaesthesiol Scand. Sep 2000;44(8):910-8. [Medline].
Kost RG, Straus SE. Postherpetic neuralgia--pathogenesis, treatment, and prevention. N Engl J Med. Jul 4 1996;335(1):32-42. [Medline].
Schmader K. Herpes zoster in older adults. Clin Infect Dis. May 15 2001;32(10):1481-6. [Medline].
Jemsek J, Greenberg SB, Taber L, Harvey D, Gershon A, Couch RB. Herpes zoster-associated encephalitis: clinicopathologic report of 12 cases and review of the literature. Medicine (Baltimore). Mar 1983;62(2):81-97. [Medline].
Pevenstein SR, Williams RK, McChesney D, Mont EK, Smialek JE, Straus SE. Quantitation of latent varicella-zoster virus and herpes simplex virus genomes in human trigeminal ganglia. J Virol. Dec 1999;73(12):10514-8. [Medline]. [Full Text].
Pavan-Langston D. Herpes zoster ophthalmicus. Neurology. Dec 1995;45(12 Suppl 8):S50-1. [Medline].
Sweeney CJ, Gilden DH. Ramsay Hunt syndrome. J Neurol Neurosurg Psychiatry. Aug 2001;71(2):149-54. [Medline]. [Full Text].
Marin M, Meissner HC, Seward JF. Varicella prevention in the United States: a review of successes and challenges. Pediatrics. Sep 2008;122(3):e744-51. [Medline].
Whitley RJ. Varicella-Zoster Virus. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practices of Infectious Diseases. 7th ed. New York, NY: Churchill Livingstone; 2010:1963-69.
Gnann JW Jr, Whitley RJ. Clinical practice. Herpes zoster. N Engl J Med. Aug 1 2002;347(5):340-6. [Medline].
Schmader K, George LK, Burchett BM, Pieper CF. Racial and psychosocial risk factors for herpes zoster in the elderly. J Infect Dis. Nov 1998;178 Suppl 1:S67-70. [Medline].
Harpaz R, Ortega-Sanchez IR, Seward JF. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. Jun 6 2008;57:1-30; quiz CE2-4. [Medline].
Araújo LQ, Macintyre CR, Vujacich C. Epidemiology and burden of herpes zoster and post-herpetic neuralgia in Australia, Asia and South America. Herpes. Sep 2007;14 Suppl 2:40-4. [Medline].
Tseng HF, Smith N, Marcy SM, Sy LS, Chao CR, Jacobsen SJ. Risk factors of herpes zoster among children immunized with varicella vaccine: results from a nested case-control study. Pediatr Infect Dis J. Mar 2010;29(3):205-8. [Medline].
Nagasako EM, Johnson RW, Griffin DR, Elpern DJ, Dworkin RH. Geographic and racial aspects of herpes zoster. J Med Virol. 2003;70 Suppl 1:S20-3. [Medline].
Dworkin RH, Johnson RW, Breuer J, Gnann JW, Levin MJ, Backonja M, et al. Recommendations for the management of herpes zoster. Clin Infect Dis. Jan 1 2007;44 Suppl 1:S1-26. [Medline].
Ozcan A, Senol M, Saglam H, et al. Comparison of the Tzanck test and polymerase chain reaction in the diagnosis of cutaneous herpes simplex and varicella zoster virus infections. Int J Dermatol. Nov 2007;46(11):1177-9. [Medline].
Berry JD, Petersen KL. A single dose of gabapentin reduces acute pain and allodynia in patients with herpes zoster. Neurology. Aug 9 2005;65(3):444-7. [Medline].
[Best Evidence] Dworkin RH, Barbano RL, Tyring SK, Betts RF, McDermott MP, Pennella-Vaughan J, et al. A randomized, placebo-controlled trial of oxycodone and of gabapentin for acute pain in herpes zoster. Pain. Apr 2009;142(3):209-17. [Medline].
[Best Evidence] Irving G, Jensen M, Cramer M, Wu J, Chiang YK, Tark M, et al. Efficacy and tolerability of gastric-retentive gabapentin for the treatment of postherpetic neuralgia: results of a double-blind, randomized, placebo-controlled clinical trial. Clin J Pain. Mar-Apr 2009;25(3):185-92. [Medline].
Lin PL, Fan SZ, Huang CH, et al. Analgesic effect of lidocaine patch 5% in the treatment of acute herpes zoster: a double-blind and vehicle-controlled study. Reg Anesth Pain Med. Jul-Aug 2008;33(4):320-5. [Medline].
De Benedittis G, Lorenzetti A. Topical aspirin/diethyl ether mixture versus indomethacin and diclofenac/diethyl ether mixtures for acute herpetic neuralgia and postherpetic neuralgia: a double-blind crossover placebo-controlled study. Pain. Apr 1996;65(1):45-51. [Medline].
Semel D, Murphy TK, Zlateva G, Cheung R, Emir B. Evaluation of the safety and efficacy of pregabalin in older patients with neuropathic pain: results from a pooled analysis of 11 clinical studies. BMC Fam Pract. Nov 5 2010;11:85. [Medline]. [Full Text].
Huff JC, Bean B, Balfour HH Jr, et al. Therapy of herpes zoster with oral acyclovir. Am J Med. Aug 29 1988;85(2A):84-9. [Medline].
Degreef H. Famciclovir, a new oral antiherpes drug: results of the first controlled clinical study demonstrating its efficacy and safety in the treatment of uncomplicated herpes zoster in immunocompetent patients. Int J Antimicrob Agents. 1994;4(4):241-6. [Medline].
Tyring S, Barbarash RA, Nahlik JE, et al. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial. Collaborative Famciclovir Herpes Zoster Study Group. Ann Intern Med. Jul 15 1995;123(2):89-96. [Medline].
Beutner KR, Friedman DJ, Forszpaniak C, Andersen PL, Wood MJ. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother. Jul 1995;39(7):1546-53. [Medline]. [Full Text].
Whitley RJ, Weiss H, Gnann JW Jr, Tyring S, Mertz GJ, Pappas PG, et al. Acyclovir with and without prednisone for the treatment of herpes zoster. A randomized, placebo-controlled trial. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Ann Intern Med. Sep 1 1996;125(5):376-83. [Medline].
Wood MJ, Johnson RW, McKendrick MW, Taylor J, Mandal BK, Crooks J. A randomized trial of acyclovir for 7 days or 21 days with and without prednisolone for treatment of acute herpes zoster. N Engl J Med. Mar 31 1994;330(13):896-900. [Medline].
Kumar V, Krone K, Mathieu A. Neuraxial and sympathetic blocks in herpes zoster and postherpetic neuralgia: an appraisal of current evidence. Reg Anesth Pain Med. Sep-Oct 2004;29(5):454-61. [Medline].
Ahmed HE, Craig WF, White PF, et al. Percutaneous electrical nerve stimulation: an alternative to antiviral drugs for acute herpes zoster. Anesth Analg. Oct 1998;87(4):911-4. [Medline].
Strasfeld L, Chou S. Antiviral drug resistance: mechanisms and clinical implications. Infect Dis Clin North Am. Sep 2010;24(3):809-33. [Medline].
Decroix J, Partsch H, Gonzalez R, et al. Factors influencing pain outcome in herpes zoster: an observational study with valaciclovir. Valaciclovir International Zoster Assessment Group (VIZA). J Eur Acad Dermatol Venereol. Jan 2000;14(1):23-33. [Medline].
Kurokawa I, Kumano K, Murakawa K. Clinical correlates of prolonged pain in Japanese patients with acute herpes zoster. J Int Med Res. Jan-Feb 2002;30(1):56-65. [Medline].
Wood MJ, Shukla S, Fiddian AP, Crooks RJ. Treatment of acute herpes zoster: effect of early (< 48 h) versus late (48-72 h) therapy with acyclovir and valaciclovir on prolonged pain. J Infect Dis. Nov 1998;178 Suppl 1:S81-4. [Medline].
van Wijck AJ, Opstelten W, Moons KG, et al. The PINE study of epidural steroids and local anaesthetics to prevent postherpetic neuralgia: a randomised controlled trial. Lancet. Jan 21 2006;367(9506):219-24. [Medline].
Ahmed AM, Brantley JS, Madkan V, Mendoza N, Tyring SK. Managing herpes zoster in immunocompromised patients. Herpes. Sep 2007;14(2):32-6. [Medline].
Balfour HH Jr, Bean B, Laskin OL, et al. Acyclovir halts progression of herpes zoster in immunocompromised patients. N Engl J Med. Jun 16 1983;308(24):1448-53. [Medline].
Colin J, Prisant O, Cochener B, Lescale O, Rolland B, Hoang-Xuan T. Comparison of the efficacy and safety of valaciclovir and acyclovir for the treatment of herpes zoster ophthalmicus. Ophthalmology. Aug 2000;107(8):1507-11. [Medline].
Tyring S, Engst R, Corriveau C, Robillard N, Trottier S, Van Slycken S, et al. Famciclovir for ophthalmic zoster: a randomised aciclovir controlled study. Br J Ophthalmol. May 2001;85(5):576-81. [Medline]. [Full Text].
Marin M, Güris D, Chaves SS, Schmid S, Seward JF. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. Jun 22 2007;56:1-40. [Medline].
Dworkin RH, Schmader KE. Treatment and prevention of postherpetic neuralgia. Clin Infect Dis. Apr 1 2003;36(7):877-82. [Medline].
Whitley RJ, Volpi A, McKendrick M, Wijck A, Oaklander AL. Management of herpes zoster and post-herpetic neuralgia now and in the future. J Clin Virol. May 2010;48 Suppl 1:S20-8. [Medline].
Wu CL, Raja SN. An update on the treatment of postherpetic neuralgia. J Pain. Jan 2008;9(1 Suppl 1):S19-30. [Medline].
Jackson JL, Gibbons R, Meyer G, Inouye L. The effect of treating herpes zoster with oral acyclovir in preventing postherpetic neuralgia. A meta-analysis. Arch Intern Med. Apr 28 1997;157(8):909-12. [Medline].
Tyring SK, Beutner KR, Tucker BA, Anderson WC, Crooks RJ. Antiviral therapy for herpes zoster: randomized, controlled clinical trial of valacyclovir and famciclovir therapy in immunocompetent patients 50 years and older. Arch Fam Med. Sep-Oct 2000;9(9):863-9. [Medline].
Alper BS, Lewis PR. Does treatment of acute herpes zoster prevent or shorten postherpetic neuralgia?. J Fam Pract. Mar 2000;49(3):255-64. [Medline].
Dworkin RH, Boon RJ, Griffin DR, Phung D. Postherpetic neuralgia: impact of famciclovir, age, rash severity, and acute pain in herpes zoster patients. J Infect Dis. Nov 1998;178 Suppl 1:S76-80. [Medline].
Acosta EP, Balfour HH Jr. Acyclovir for treatment of postherpetic neuralgia: efficacy and pharmacokinetics. Antimicrob Agents Chemother. Oct 2001;45(10):2771-4. [Medline]. [Full Text].
Kotani N, Kushikata T, Hashimoto H, et al. Intrathecal methylprednisolone for intractable postherpetic neuralgia. N Engl J Med. Nov 23 2000;343(21):1514-9. [Medline].
Oxman MN. Zoster vaccine: current status and future prospects. Clin Infect Dis. Jul 15 2010;51(2):197-213. [Medline].
[Best Evidence] Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. Jun 2 2005;352(22):2271-84. [Medline].
Schmader K, Levin M, Gnann J, McNeil S, Vesikari T, et al. Efficacy, immunogenicity, safety, and tolerability of zoster vaccine (ZV) in subjects 50 to 59 years of age (Poster/Abstract). Infectious Diseases Society of America. The 48th Annual Meeting of the Infectious Diseases Society of America. 10-21-2010;Vancouver, British Columbia, Canada:Ref Type: Abstract: 3363.
Print
