Cold Sore - Guidelines for Prescribing Oral Antivirals

Description
  • Cold sores (herpes labialis, fever blisters) are the manifestation of recurrent HSV (herpes simplex virus-1 or 2)  around the mouth. It is most commonly transmitted via saliva.

  • About 20 to 40% of patients who experience a primary herpes infection develop subsequent recurrent herpes infections caused by reactivation of HSV that remains latent in neural ganglion cells.

  • Common problem affecting 20 to 40% of the general population, and approximately 33% of school age children.

  • Triggers:

    • sun exposure
    • stress surgical trauma
    • dental extractions
    • menses and other hormonal changes
    • infectious febrile conditions
    • hyperthermia
    • stress
    • Upper respiratory tract infection
  • Risk factors:
    • Female sex
    • Older age (>65)
    • Caucasian
    • Weakened immune system
  • For more information and photos, go to:

Signs and Symptoms
  • Typically a painful, unilateral vesicular lesion surrounded by erythema, appearing on the vermilion border of the lip and on the border between skin and mucosa around the nostrils. The vesicles break, leaking a clear, sticky fluid, then crust over and heal without scarring within 7 to 10 days.

  • Prodromal tingling and burning sensation in the location of the eruption may occur 2 to 24 hours before the appearance of the vesicle, but this does not occur in all cases.

  • Patients complain of pain, unsightly appearance and possibly itching.

  • Transmission up to 60 hours after initial symptoms, but still possible until lesions are fully healed and no longer producing exudate.

  • Systemic symptoms are unusual and should cause suspicion for another condition.
Differential Assessments

Orolabial herpes (cold sore) is diagnosed based on the presence of typical signs and symptoms (listed above). Rule out the following conditions that may present with similar signs / symptoms:

  • Impetigo - a bacterial infection most commonly caused by staphylococcus aureus.  Can cause pustules to form around the mouth.  It will be non-inflamed and the lesions will have honey-coloured crusts, contrast to the clear crusts seen with cold sores.

  • Canker sores - lesions that occur on the inside of lips and are not preceded by formation of a vesicle.  Will not occur on external lip.

  • Angular cheilitis - inflammation that occurs on the corners of the mouth, which can resemble a cold sore.  However, angular cheilitis will not cause any lesions to form.

  • Chicken pox - presence of typical lesions on skin and mucous membranes, spread to head, trunk and extremities. Lesions can occur rarely on the mucocutaneous border of the lip, which resemble cold sore lesions, but lesions will be present elsewhere as well.

  • Shingles (Herpes zoster) - clinical diagnosis is based on vesicular eruption on one side only, often with prodromal pain which may involve sensory nerves and overlying skin of head, trunk or limbs. Lesions on or around nose may involve the eye (herpes keratitis) and require immediate assessment by patient's primary care provider.

  • Mononucleosis which usually involves close contact with other infected persons and includes generalized swollen lymph nodes, especially in the neck and groin. Fever is also possible.  Blisters may occur on the lips which resemble a cold sore lesion. Refer to patient's primary care provider for blood tests and diagnosis.

  • Basal cell carcinoma - non-healing lesions which may resemble cold sores on face.  Suspect this if the lesion has not healed or change over 10 days.

  • Stevens-Johnson syndrome - a fever causing, skin-peeling reaction in response to a drug.

  • Syphilis - a painless sore on the lips or in the mouth occurring 10 days to 3 months after contact with infected person.  Since they are painless and not itchy, this helps differentiate them from a cold sore. Refer to patient's primary care provider for diagnosis and antibiotic treatment.

When to Refer

Patients with typical cold sore signs / symptoms usually do not require further investigation, however an assessment by the patient's primary care provider may be required in the following situations

  • First cold sore and accompanied by fever, malaise, pharyngitis or stomatitis
    • May be primary infection of herpes labialis; longer duration of anti-viral treatment may be indicated
  • Lesion present for greater than 14 days

  • Accompanied by symptoms of systemic illness (fever, swollen glands)

  • Patient is immunocompromised (drug or disease)

  • Lesion appears infected - excessively red, swollen, or contains pus

  • Age less than 2
  • Ocular involvement
  • Frequent recurrences (>6 per year), since chronic prophylactic therapy may be more appropriate.
  • Unable to confirm patient's diagnosis of cold sore and more serious condition (see Differential Assessment above) is suspected. Refer to patient's primary care provider for further investigation and supervised therapy.

Treatment

Non-pharmacological treatment

  • Patients should keep the area clean using mild soap and water and avoid touching the lesion to prevent autoinnoculation and spread of HSV.

  • Avoid kissing or oral sex until all lesions completely healed.

  • Do not share personal items in contact with lesions (eg. lip balm).

  • Extra caution with contact lens use, as they may transfer the infection to the eye if hand-hygiene is not followed.

  • Cold or warm compresses can help clean the area and improve the appearance of the lesions.

Over-the-counter drug options

  • Pharmacists can recommend protectants such as petrolatum, zinc oxide, cocoa butter, allantoin or calamine to prevent cracking and drying. If a secondary bacterial infection occurs, refer to patient's primary care provider.

  • Local anesthetics can offer temporary relief from pain and itching and may shorten duration of lesions and reduce eruptions as well. Examples are Zilactin™ which contains benzocaine and Zilactin L™ which contains lidocaine.

  • Docosonal 10% is in Abreva™ and appears to block viral entry by inhibiting fusion between lipid-enveloped viruses and plasma membrane of the host cell.

  • Lipactin™ contains zinc and heparin. It may reduce pain and increase rate of healing of lesions, although there are no studies to support this.

  • Sunscreens are useful adjuncts in preventing sun-induced recurrences.

Prescription drug option

Oral Antivirals

  • Can be prescribed for treatment of recurrent orolabial herpes ocurring in immunocompetent adults (level 1 evidence).
  • There are no published trials evaluating the use of valacyclovir or famciclovir for orolabial herpes in children <12 years of age. Only acyclovir has an official indication for orolabial herpes in children 2 years of age and older.

  • Treatment should be started within 1 - 2 hours after onset of first symptoms (tingling, itching or burning) or as soon as possible. Oral antivirals are ineffective if started after the lesions appear.

  • Reduces the duration of symptoms by an average of one to two days, reduces pain and itch, and improves apeparance.  Will not abort a lesion entirely.

  • Many patients have only occasional recurrences of cold sores with minimal symptoms; antiviral therapy is not necessary for these patients

  • Only consider prescription treatment if the patient has a well-defined prodrome and lesions have not yet formed.  If lesions have formed, patients may be issued a prescription to keep on hand to facilitate early initiation of therapy for future episodes.
  • Oral anti-virals indicated for cold sore treatment

    • ACYCLOVIR: 400mg 5 times per day for 5 days (adults); 15mg/kg (max of 200mg per dose) 5 times per day for 5 days

    • VALACYCLOVIR: 2000 mg BID for 2 doses (every 12 hours)

    • FAMCICLOVIR: 750mg BID for 2 doses (every 12 hours) or one dose of 1500 mg

  • Suppressive therapy with acyclovir may also be prescribed if there is a known trigger for the patient's cold sores (eg. sun exposure)
    • Acyclovir 400mg BID beginning 12h prior to trigger exposure and for duration of exposure

  • Renal dosing:

Famciclovir

CrCl ≥60 mL/minute: No dosage adjustment necessary

CrCl 40-59 mL/minute: Administer 750 mg as a single dose

CrCl 20-39 mL/minute: Administer 500 mg as a single dose

CrCl <20 mL/minute: Administer 250 mg as a single dose

Acyclovir

CrCl 10-25 mL/minute: 400 mg every 8 hours

CrCl <10 mL/minute: 400 mg every 12 hours

Valacyclovir

CrCl 30-49 mL/minute: 1 g every 12 hours for 2 doses

CrCl 10-29 mL/minute: 500 mg every 12 hours for 2 doses

CrCl <10 mL/minute: 500 mg as a single dose

  • Pregnancy: acyclovir and valacyclovir can be used during pregnancy; insufficient data available to evaluate famciclovir safety.
  • Lactation: acyclovir and valacyclovir are rated as compatible with breastfeeding; insufficient data available on the safety of famciclovir.

Topical Antiviral

  • Acyclovir 5% / hydrocortisone 1% cream (Xerese®) is now available to prescribe
  • Must be started within prodromal phase, as with oral antivirals.
  • Applied five times daily for 5 days
  • Topical antivirals are slightly less effective versus oral antivirals.  Topical antivirals will reduce lesion duration by about one day, versus one to two days with oral antivirals.
  • Better tolerated by some patients
  • Combining with oral antivirals shown to have NO additional benefit
General Advice / Monitoring
Advice on minimising the spread of the infection
  • Try to avoid touching your cold sores, unless you are applying a cream. Creams should be dabbed on gently rather than rubbed in, as this can damage your skin further.

  • Always wash your hands before, and after, applying cream, and after touching the affected area.

  • Do not share creams with others because this can cause the infection to spread.

  • Do not share items that come into contact with the affected area, such as lipsticks, or cutlery.

  • Avoid kissing or oral sex, until your cold sores have completely healed.

  • If you have a cold sore, be particularly careful around newborn babies, pregnant women, and people with a low immune system such as those who have been undergoing chemotherapy, or those with HIV.

Preventing recurrent outbreaks of cold sores

  • If you know what usually triggers your cold sores, try to avoid these triggers if possible. For example, a sun block lip balm (SPF 15 or higher) may help to prevent cold sores triggered by bright sunlight.

  • There is no benefit in using an antiviral cream continuously to try and prevent future bouts of cold sores. They cannot cure the virus, and will only be effective once the virus has been triggered.

  • For individuals in whom orolabial herpes is reactivated by exposure to sunlight, oral acyclovir 400 mg BID begun 12 hours prior to sun exposure, with frequent sunscreen use, prevents attacks. Prophylaxis is continued for the duration of sun exposure.

Assess Benefit

  • Follow-up with patient after 7 days.

  • If symptoms are not resolved, refer to patient's primary care provider.

  • If symptoms are resolved, advise on prevention strategies above.

  • Patients who have frequent episodes of cold sore may be given a prescription for an antiviral to keep on hand for future episodes.

Assess Adverse Effects

  • Oral antivirals are well tolerated; frequency of adverse effects similar to placebo.  Some may experience a mild headache.
Products

Detailed information on contraindications, cautions, adverse effects and interactions is available in individual drug monographs in the CPS (e-CPS), Lexi-Comp, AHFS, www.drugs.com or other reliable drug monograph references. For comprehensive drug comparisons, see RxFiles charts (www.rxfiles.ca).
This information should be routinely consulted before prescribing.

 

 

Generic Name

Valacyclovir

    500mg tablet

   1000mg tablet

Famciclovir

   250mg tablet
   500mg tablet
Acyclovir
   400mg tablet
Acyclovir 5% / Hydrocortisone 1% cream
Prescribing and Billing Details
  • pseudoDIN: 00951088
    • Max of 8 claims per 365 days per patient

  • May prescribe sufficient quantity to treat ONE cold sore.  No refills.
    • If patient presents with a cold-sore beyond the pro-dromal stage, you may still prescribe enough tablets to treat the next episode
    • Each cold sore is to be treated as a distinct episode and re-assessed
    • If exposure to a known trigger is expected, you may prescribe suppressive therapy with acyclovir

  • Only products with an official indication for cold sores from Health Canada or reliable infectious diseases guidelines are approved for pharmacist prescribing.
    Note topical Zovirax (acyclovir 5% cream and ointment) is not approved for cold sore treatment by Health Canada
Treatment Flowchart
Pharmacist Assessment Documents
References / Suggested Reading
  1. Evans G. Herpesvirus infections.  In RxTx - CTC online. Available at www.e-therapeutics.ca (by subscription).
  2. Conklin J. Cold sores (Herpes labialis). In RxTx - CTMA. Available at www.e-therapeutics.ca  (by subscription).
  3. Pray WS. Preventing and Treating Cold Sores.  In Medscape. Free access at http://www.medscape.com/viewarticle/557162.
  4. Opstelten W, Neven A, Eekhof J. Treatment and prevention herpes labialis Canadian Family Physician 2008;54:1683-7.  Available at http://www.cfp.ca/content/54/12/1683.full  ( free access).
  5. Klein, Robyn. Treatment of herpes simplex virus type 1 infection in immunocompetent patients. In UpToDate online. Available at  www.uptodate.com (by subscription).
  6. Oral herpes. In Dynamed online. Available at www.dynamed.com  (by subscription).

Prepared by medSask.
Reviewed by Dr. Yvonne Shevchuk, College of Pharmacy & Nutrition.

Funded by the Saskatchewan College of Pharmacy Professionals.
Posted May 2010; Updated May 2017.