What to Expect on Day 1 of Cold Sore Medication and When to Expect Relief

Cold sores, sometimes called fever blisters, are an uncomfortable nuisance. And while there is no cure for the herpes simplex virus (HSV) that causes cold sores, medications can help shorten the healing process. Keep reading to learn more about medicines that relieve these painful, small blisters.

How Long Does It Usually Take for Medication to Start Working on a Cold Sore?

Cold sores can heal without medication in about two weeks. The time it usually takes for medicines to work depends on the type you use. For example, a prescription antiviral medication will begin working soon after the first dose, while an OTC topical cream can take up to five days to see results. Remedies are available to treat cold sores over the counter (OTC) or by prescription.

Over-the-Counter Treatments

OTC medications may be your first line of defense against painful cold sores. These products are readily available at your local pharmacy without a prescription, and you can begin taking them immediately. OTC treatments come in topical creams or gels.

Anesthetic agents, such as benzocaine, lidocaine, and prilocaine, can help decrease the pain of a cold sore by numbing the affected area. If you use an anesthetic gel, follow the medication instructions. You can use a cotton swab to control the amount of gel you apply on your cold sores. Lidocaine relieves pain in about two days, while benzocaine and prilocaine can take up to five days to work.

Antiviral creams, such as Docosanol, are available OTC. Unlike anesthetic gels, Docosanol prevents the cold-sore virus from growing and spreading to healthy tissues. However, the cream does not prevent cold sores from spreading to other people. Docosanal usually takes about two to three days to work, depending on the stage of the cold sore.

Other OTC creams like zinc oxide and glycine also treat cold sores. Both help reduce cold sore symptoms in about five days. However, you must use these creams within 24 hours of the first signs of a cold sore outbreak. Tingling and burning are just a few symptoms you may experience before small blisters form around your mouth or on your lips.

Oral pain relievers, such as acetaminophen, can reduce the pain and discomfort of a cold sore. Fortunately, there are plenty of OTC treatments available. Check with your local pharmacist to learn which one is best for you.

Prescription Medications

You may consider prescription medication to help relieve your cold sore symptoms. An antiviral medication speeds up recovery. You should speak with your healthcare provider if you develop cold sores and have health conditions that weaken the immune system. Ongoing treatments such as chemotherapy or immunosuppressive drugs can decrease your body's natural ability to stave off infections like cold sores. Make a dermatology appointment for treatment for conditions like atopic dermatitis or eczema.

Prescription-strength antiviral medications come in pill or topical cream form and are only available with a prescription from a healthcare provider. The common antiviral drugs prescribed for cold sore treatment include Valacyclovir, Famciclovir, and Penciclovir.

For healthy adults and children over 12 years old, the one-day dose of valacyclovir, two pills taken 12 hours apart, is the typical treatment for cold sores. People with kidney disease must use a lower dose to allow their kidneys to process the drug effectively. Famciclovir treats cold sores caused by HSV-1 with a single-dose pill. However, if you have HSV-2, the virus that causes genital herpes, famciclovir requires seven days of treatment. Penciclovir is an antiviral topical cream that works well for cold sores and is safe for pregnant women.

What Can I Expect to Happen on Day 1 of Medication for a Cold Sore?

The prescription antiviral medications listed above begin to work on the first day. However, you may not see a noticeable change in your cold sores during that time. You can take oral prescription drugs such as valacyclovir and famciclovir over the course of one day. If you already have fluid-filled blisters, Docosanol can take up to two to three days before you can see visible results. 

The effectiveness of a cold sore treatment depends on the following:

  • When you begin treatment
  • Type of medication
  • Over-the-counter remedy
  • Prescription drugs
  • First-time exposure to HSV
  • Recurrent cold sore outbreak

When you take antiviral medicine during the prodromal phase of an HSV infection, the drug can prevent cold sores from developing. Knowing what triggers cold sores, you can proactively prevent an outbreak with medication. Cold sore triggers include the following:

  • Fever
  • Psychological stress
  • Illness such as a cold or flu
  • Other viral infections, such as an upper respiratory infection
  • Hormonal fluctuations
  • Sun exposure
  • Dental work

Whether you treat your cold sores with OTC medication or prescription drugs, the recovery time is less than it usually takes to heal on your own.

Are There Any Potential Side Effects of Taking Medication for a Cold Sore?

Like most medications, antivirals have some side effects, and some are serious. The drug dose, frequency, and amount of time you take the medication can impact the severity of the side effects. Not all people taking antiviral medicine will experience the following side effects:

  • Allergic reaction
  • Nausea and vomiting
  • Kidney problems
  • Agitation
  • Skin irritation from topical medication
  • Dry month
  • Headache
  • Rash
  • Sore throat
  • Joint and muscle pain
  • Blood in urine

As with all OTC and prescription medications, please ensure you read and follow directions for your safety. Let your healthcare provider know if you have any known allergies, food or otherwise. Also, if you are pregnant or breastfeeding, check for special instructions before taking the medicine.

When Should I Expect My Cold Sore to Disappear After Taking Medication?

Begin antiviral medication at the first signs of an outbreak to prevent cold sores from developing altogether. Signs and symptoms before cold sores are visible include itching, pain, tingling, or burning around the mouth or on the lips.

Topical creams such as penciclovir work soon after you apply the medicine to the area. However, the cold sore doesn't disappear immediately. The drug stops the virus from growing, and the cold sore goes away only half a day quicker than without medication. Famciclovir and valacyclovir relieve cold sore symptoms in about four days. Remember, the virus that causes cold sores can still be transmitted through skin-to-skin contact, such as kissing during treatment, even if you take medicine to speed up your recovery and heal completely.


Cold sores can heal on their own without medication. However, there may be circumstances where you need a little support from an OTC or prescription medication.


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American Academy of Dermatology Association. (n.d.). Cold sores: Overview.

Cleveland Clinic (n.d.). Cold sores. Retrieved June 6, 2023, from

GoodRx. (2021, March 7). Penciclovir.

Jacobsen, S. (2022, December 13). Valacyclovir dosages: Your GoodRx guide. GoodRx. Retrieved June 6, 2023, from

Leonard, B. (2023, June 2). 6 Valacyclovir (Valtrex) side effects you should know about. GoodRx.

Silver, N. (2023, March 27). Cold sore stages: What can I do? Healthline. 

World Health Organization. (2023, April 5). Herpes simplex virus.

Kimberly Madison

Author Bio

Kimberly Madison, MS, RN, is a freelance health content writer with over 13 years of experience as a registered nurse. She creates high-quality blog content, health news articles, web copy, infographics, and patient education materials for hospitals and healthcare brands.