Valacyclovir (VALTREX), Penciclovir (DENAVIR), and Docosanol (ABREVA) – How Much is One Day Without a Cold Sore Worth?

The editors of the highly respected Medical Letter On Drugs and Therapeutics, an independent source of drug information written for physicians and pharmacists, reviewed the use of the antiviral drug valacyclovir (VALTREX) for the treatment of cold sores (herpes labialis) in their November 11, 2002 issue. This prompted us to evaluate two other Food and Drug Administration (FDA) approved drugs, penciclovir (DENAVIR) and docosanol (ABREVA), together with valacyclovir for cold sore treatment.

The most common herpes viruses are Herpes Simplex 1 (HSV-1) and Herpes Simplex 2 (HSV-2). Usually HSV-1 causes cold sores or fever blisters, and HSV-2 causes genital herpes. But herpes viruses can cause outbreaks in either area. Other common herpes infections include chickenpox (varicella-zoster) and shingles (herpes zoster).

A person’s first cold sore often goes unnoticed, but the virus apparently remains dormant in the cells. About half of all people who have experienced a cold sore will encounter another one at some unpredictable later time.

Cold sores are often preceded by burning, itching, tingling, or numbness in the area where the cold sore is developing. A mature cold sore often has a crust overlying a red, inflamed area. The presence of pus under the crust may indicate that a bacterial infection has developed. The herpes simplex virus is contagious and thought to be transmittable by direct contact – watch the kissing! The fluid from cold sores contains live viruses and may serve to transmit them from person to person.

In the vast majority of people with normal immune systems cold sores are a mild condition that heal on their own within several days and are a cosmetic rather than a medical problem.

Valacyclovir (VALTREX)

Valacyclovir was cleared by the FDA in September 2002 for the one-day treatment of cold sores in patients 12 years of age and older. The drug had previously been approved for the suppression and treatment of genital herpes and the treatment of shingles.

Valacyclovir is rapidly converted in the body to the older drug acyclovir (ZOVIRAX) which is not approved for cold sores, though it is being reviewed by the FDA for this use. Both valacyclovir and acyclovir are manufactured by GlaxoSmithKline of North Carolina.

The basis for approving valacyclovir was two clinical trials conducted in 1,856 healthy adults and adolescents (12 years old) with a history of recurrent cold sores. Patients self initiated treatment at the earliest symptoms and prior to any signs of a cold sore. This was usually within two hours of onset of symptoms. The average duration of cold sore episodes was about one day shorter in patients receiving valacyclovir compared to placebo. Treatment for two days did not offer additional benefit over the one day regimen.

Gastrointestinal adverse effects, headache and rash were seen in clinical trials with the drug. Valacyclovir can cause a life-threatening blood disorder when taken in high doses in patients with compromised immune systems.

The Medical Letter editors concluded their review of the drug by saying “Oral valacyclovir (Valtrex) begun with the first symptoms of herpes labialis, like other drugs already available, can modestly shorten the duration of an episode.”

The FDA approved dose for valacyclovir is two grams by mouth every 12 hours for one day. The cost of two grams of the drug is $19.97 at a Washington DC chain pharmacy and will shorten on average a cold sore by about one day.

Penciclovir (DENAVIR)

We reviewed penciclovir (DENAVIR) cream in the August 1997 Worst Pills, Best Pills News and found it shortened the duration of a cold sore by about one day and was very expensive. Enough penciclovir to treat one cold sore currently has a price tag of $31.09.

Penciclovir cream was compared, in two clinical studies, to a placebo consisting of an inert cream. Patients with a history of three or more cold sores per year started to apply penciclovir or the placebo within one hour of the first sign or symptom of a cold sore and repeated the application every two hours while awake for four days – this amounted to about nine applications per day.

In the first study, cold sore pain stopped in an average of 3.5 days in those using penciclovir and in 4.1 days for the placebo group, a difference of about one-half a day. It took on average 5.5 days for the cold sores to heal in those using placebo vs. 4.8 days in those using penciclovir — an advantage of about three-quarters of a day for the drug. In the second trial, pain relief from the cold sore occurred on average about one day sooner with penciclovir than with the placebo cream, and cold sores healed in an average of 4.4 days with penciclovir and 5.3 days with the placebo, also a difference of about one day.

Docosanol (ABREVA)

Docosanol is an over-the-counter (OTC) cream approved by the FDA in July 2000 for cold sores and is sold by GlaxoSmithKline.

We examined the FDA reviews of the data submitted by docosanol’s manufacturer to gain approval for the drug and found it remarkable that the drug was ever approved. By mid-1996, docosanol had failed in three clinical trials to show a statistically significant difference in cold sore healing time compared to a placebo. In two of these trials, the placebo was better than docosanol by 0.2 and 0.1 days. The third trial found that docosanol treated cold sores resolved 0.2 days faster than the placebo. This is a difference of 4.8 hours. Repeatedly, the FDA Medical Officer and statisticians recommended against the drug’s approval.

The company ultimately submitted additional studies to the FDA and after some dispute was able to convince the agency that they had completed two clinical trials with positive results, the usual standard for approval, in favor of docosanol over placebo.

The best estimate of the effectiveness is that a cold sore will heal about one-half day sooner if it is applied starting with the first signs or symptoms of a cold sore five times a day until the cold sore is healed. This will cost $16.99 at a Washington DC chain pharmacy.

The table below summarizes the costs and the very modest effectiveness of these three drugs. Because the majority of use of these drugs is cosmetic rather than medical, it is impossible for us to recommend any of them. When the medical benefit of a drug is close to zero, the risks no matter how small, in addition to the costs, will always outweigh the benefit.

What You Can Do

If you decide not to spend the money for one of these drugs every time a cold sore appears, there are things you can do to control discomfort, allowing healing and avoid complications. The cold sore should be kept moist to prevent drying and cracking, which may allow bacterial infection to develop, thus delaying healing. Skin protectors such as petroleum jelly (VASELINE) will relieve dryness and keep the sores soft. Applying local pain relievers (anesthetics) containing drugs such as benzocaine can reduce discomfort. The cold sore should also be kept clean by gently washing with soap and water.