Denavir

Before using penciclovir,

• tell your doctor and pharmacist if you are allergic to penciclovir, acyclovir (Zovirax), or any other drugs.
• tell your doctor and pharmacist what prescription and nonprescription medications you are taking, including vitamins.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking penciclovir, call your doctor.

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

• Denavir^®

Contraindications

Hypersensitivity

Cautions

Use gloves to apply because may inoculate other areas

External use only

Effects in immunocompromised patients not established

For use in lips/face only

NOT for use in mucous membranes not recommended

NOT for use in or near eyes

Since penciclovir is poorly absorbed following oral administration, adverse reactions related to penciclovir ingestion are unlikely. There is no information on overdose.

• Fever
• Genital Herpes in Women (Symptoms, Signs, Treatment)

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Do not apply penciclovir topical to the inside of the nose or in or near the eyes.

You should not use penciclovir topical if you are allergic to it.

Penciclovir topical is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant.

It is not known whether penciclovir topical passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Penciclovir topical is not approved for use by anyone younger than 12 years old.

• Importance of using penciclovir cream only for treatment of recurrent herpes labialis (orofacial or orolabial herpes, cold sores, fever blisters) on the lips and surrounding symptomatic skin on the face (e.g., areas with tingling).1

• Importance of avoiding application in or near the eyes.1

• Advise patients that the cream is not a cure for cold sores and that not all patients respond to treatment with the cream.1

• Importance of starting treatment at the earliest sign of a cold sore (i.e., tingling, redness, itching, bump).1

• Advise patients to ensure that their face is clean and dry prior to application of the cream and to wash their hands with soap and water prior to and after application.1

• Advise patients not to use the cream if they have had an allergic reaction to the drug or any ingredient in the formulation.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

• Importance of advising patients of other important precautionary information.1 (See Cautions.)

• Tell all of your health care providers that you take Denavir. This includes your doctors, nurses, pharmacists, and dentists.
• Talk with your doctor before you use other drugs or products on your skin.
• Do not use longer than you have been told. A second infection may happen.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Use Denavir as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Keep using this medicine as you have been told by your doctor or other health care provider, even if you feel well.
• Do not take Denavir by mouth. Use on your skin only. Keep out of your mouth, nose, and eyes (may burn).
• Wash your hands before and after use.
• Clean affected part before use. Make sure to dry well.
• Use a rubber glove to put on.
• Put a thin layer on the affected skin and rub in gently.
• Use at the first sign of a cold sore.

What do I do if I miss a dose?

• Use a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not use 2 doses or extra doses.

5.1       General

Denavir should only be used on herpes labialis on the lips and face. Because no data are available, application to human mucous membranes is not recommended. Particular care should be taken to avoid application in or near the eyes since it may cause irritation. Lesions that do not improve or that worsen on therapy should be evaluated for secondary bacterial infection. The effect of Denavir has not been established in immunocompromised patients.

Denavir (penciclovir) cream 1% contains penciclovir, an antiviral agent active against herpes viruses. Denavir is available for topical administration as a 1% white cream. Each gram of Denavir contains 10 mg of penciclovir and the following inactive ingredients: cetostearyl alcohol, mineral oil, polyoxyl 20 cetostearyl ether, propylene glycol, purified water and white petrolatum.
Chemically, penciclovir is known as 9-[4-hydroxy-3-(hydroxymethyl)butyl] guanine. Its molecular formula is C10H15N5O3; its molecular weight is 253.26. It is a synthetic acyclic guanine derivative and has the following structure:

Figure 1: Structural Formula of Penciclovir

Penciclovir is a white to pale yellow solid. At 20°C it has a solubility of 0.2 mg/mL in methanol, 1.3 mg/mL in propylene glycol, and 1.7 mg/mL in water. In aqueous buffer (pH 2) the solubility is 10.0 mg/mL.  Penciclovir is not hygroscopic. Its partition coefficient in n-octanol/water at pH 7.5 is 0.024 (logP = -1.62).

13.1       Carcinogenesis, Mutagenesis, Impairment of Fertility

In clinical trials, systemic drug exposure following topical administration of penciclovir cream was negligible, as the penciclovir content of all plasma and urine samples was below the limit of assay detection (0.1 mcg/mL and 10 mcg/mL, respectively).  However, for the purpose of inter-species dose comparisons presented in the following sections, an assumption of 100% absorption of penciclovir from the topically applied product has been used.  Based on the use of the maximal recommended topical dose of penciclovir of 0.05 mg/kg/day and an assumption of 100% absorption, the maximum theoretical plasma AUC0-24 hrs for penciclovir is approximately 0.129 mcg.hr/mL.

Carcinogenesis:  Two-year carcinogenicity studies were conducted with famciclovir (the oral prodrug of penciclovir) in rats and mice.  An increase in the incidence of mammary adenocarcinoma (a common tumor in female rats of the strain used) was seen in female rats receiving 600 mg/kg/day (approximately 395x the maximum theoretical human exposure to penciclovir following application of the topical product, based on area under the plasma concentration curve comparisons [24 hr. AUC]).  No increases in tumor incidence were seen among male rats treated at doses up to 240 mg/kg/day (approximately 190x the maximum theoretical human AUC for penciclovir), or in male and female mice at doses up to 600 mg/kg/day (approximately 100x the maximum theoretical human AUC for penciclovir).

Mutagenesis:  When tested in vitro, penciclovir did not cause an increase in gene mutation in the Ames assay using multiple strains of S. typhimurium or E. coli (at up to 20,000 mcg/plate), nor did it cause an increase in unscheduled DNA repair in mammalian HeLa S3 cells (at up to 5,000 mcg/mL).  However, an increase in clastogenic responses was seen with penciclovir in the L5178Y mouse lymphoma cell assay (at doses ≥1000 mcg/mL) and, in human lymphocytes incubated in vitro at doses ≥250 mcg/mL.  When tested in vivo, penciclovir caused an increase in micronuclei in mouse bone marrow following the intravenous administration of doses ≥500 mg/kg (≥810x the maximum human dose, based on body surface area conversion).

Impairment of Fertility:  Testicular toxicity was observed in multiple animal species (rats and dogs) following repeated intravenous administration of penciclovir (160 mg/kg/day and 100 mg/kg/day, respectively, approximately 1155 and 3255x the maximum theoretical human AUC).  Testicular changes seen in both species included atrophy of the seminiferous tubules and reductions in epididymal sperm counts and/or an increased incidence of sperm with abnormal morphology or reduced motility.  Adverse testicular effects were related to an increasing dose or duration of exposure to penciclovir.  No adverse testicular or reproductive effects (fertility and reproductive function) were observed in rats after 10 to 13 weeks dosing at 80 mg/kg/day, or testicular effects in dogs after 13 weeks dosing at 30 mg/kg/day (575 and 845x the maximum theoretical human AUC, respectively).  Intravenously administered penciclovir had no effect on fertility or reproductive performance in female rats at doses of up to 80 mg/kg/day (260x the maximum human dose [BSA]).

There was no evidence of any clinically significant effects on sperm count, motility or morphology in 2 placebo-controlled clinical trials of Famvir® (famciclovir [the oral prodrug of penciclovir], 250 mg b.i.d.; n=66) in immunocompetent men with recurrent genital herpes, when dosing and follow-up were maintained for 18 and 8 weeks, respectively (approximately 2 and 1 spermatogenic cycles in the human).

You should not use Denavir cream if you are allergic to penciclovir.

Penciclovir is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant.

It is not known whether penciclovir topical passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Denavir cream is not approved for use by anyone younger than 12 years old.

LactMed Record Number

379

Last Revision Date

20130907

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