Denavir
penciclovir · Cream · Topical
Uses
1 INDICATIONS AND USAGE DENAVIR is a deoxynucleoside analog HSV DNA polymerase inhibitor indicated for the treatment of recurrent herpes labialis (cold sores) in adults and children 12 years of age or older. DENAVIR ® is a deoxynucleoside analog HSV DNA polymerase inhibitor indicated for the treatment of recurrent herpes labialis (cold sores) in adults and pediatric patients12 years of age and older. ( 1 )
Dosage and administration
Apply DENAVIR every 2 hours during waking hours for a period of 4 days. Start treatment as early as possible (i.e., during the prodrome or when lesions appear).
• Apply DENAVIR every 2 hours during waking hours for a period of 4 days ( 2 ).
• Start treatment as early as possible (i.e., during the prodrome or when lesions appear). ( 2 )
Dosage forms and strengths
3 DOSAGE FORMS AND STRENGTHS DENAVIR is supplied in a 5 gram tube containing 10 mg of penciclovir per gram in a cream base, which is equivalent to 1% (w/w).
• Topical cream containing 1% penciclovir ( 3 ).
Contraindications
4 CONTRAINDICATIONS DENAVIR is contraindicated in patients with known hypersensitivity to the product or any of its components.
• Contraindicated in patients with known hypersensitivity to the product or any of its components. ( 4 )
Warnings and precautions
• Only for topical use of herpes labialis on the lips and face. ( 5 ) 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.
Side effects
• One or more local skin reactions were reported by 3% of the subjects treated with DENAVIR and 4% of placebo-treated patients. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In two double-blind, placebo-controlled trials, 1,516 patients were treated with DENAVIR (penciclovir cream) and 1,541 with placebo. One or more local adverse reactions were reported by 3% of the patients treated with DENAVIR and 4% of placebo-treated patients. The rates of reported local adverse reactions are shown in Table 1. TABLE 1 - Local Adverse Reactions Reported in Phase III Trials Penciclovir N=1,516 % Placebo N=1,541 % Application site reaction 1 2 Hypesthesia/Local anesthesia <1 <1 Taste perversion <1 <1 Rash (erythematous) <1 <1 Two studies, enrolling 108 healthy subjects, were conducted to evaluate the dermal tolerance of 5% penciclovir cream (a 5-fold higher concentration than the commercial formulation) compared to vehicle using repeated occluded patch testing methodology. The 5% penciclovir cream induced mild erythema in approximately one-half of the subjects exposed, an irritancy profile similar to the vehicle control in terms of severity and proportion of subjects with a response. No evidence of sensitization was observed. 6.2 Post-Marketing Experience The following adverse reactions have been identified during post-approval use of DENAVIR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following events have been identified from worldwide post-marketing use of DENAVIR in treatment of recurrent herpes labialis (cold sores) in adults. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to DENAVIR. General: Headache, oral/pharyngeal edema, parosmia. Skin: Aggravated condition, decreased therapeutic response, local edema, pain, paresthesia, pruritus, skin discoloration, and urticaria.
Drug interactions
No drug interaction studies have been performed with DENAVIR. Due to minimal systemic absorption of DENAVIR, systemic drug interactions are unlikely.
Use in specific populations
8.1 Pregnancy Risk Summary DENAVIR is not absorbed systemically following topical administration and maternal use is not expected to result in fetal exposure to the drug. 8.2 Lactation Risk Summary DENAVIR is not absorbed systemically by the mother following topical administration and breastfeeding is not expected to result in exposure of the child to DENAVIR. 8.4 Pediatric Use An open-label, uncontrolled trial with penciclovir cream 1% was conducted in 102 subjects, ages 12-17 years, with recurrent herpes labialis. The frequency of adverse events was generally similar to the frequency previously reported for adult patients. Safety and effectiveness in pediatric patients less than 12 years of age have not been established. 8.5 Geriatric Use In 74 subjects ≥ 65 years of age, the adverse events profile was comparable to that observed in younger patients.
Pregnancy
8.1 Pregnancy Risk Summary DENAVIR is not absorbed systemically following topical administration and maternal use is not expected to result in fetal exposure to the drug.
Pediatric use
8.4 Pediatric Use An open-label, uncontrolled trial with penciclovir cream 1% was conducted in 102 subjects, ages 12-17 years, with recurrent herpes labialis. The frequency of adverse events was generally similar to the frequency previously reported for adult patients. Safety and effectiveness in pediatric patients less than 12 years of age have not been established.
Geriatric use
8.5 Geriatric Use In 74 subjects ≥ 65 years of age, the adverse events profile was comparable to that observed in younger patients.
Overdosage
Since penciclovir is poorly absorbed following oral administration, adverse reactions related to penciclovir ingestion are unlikely. There is no information on overdose.
Description
(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 C 10 H 15 N 5 O 3 ; 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). Penciclovir Structural Formula
Mechanism of action
12.1 Mechanism of Action Penciclovir is an antiviral agent active against alpha herpes viruses [see Microbiology (12.4) ]. Mechanism of Action Penciclovir has inhibitory activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). In cells infected with HSV-1 or HSV-2, the viral thymidine kinase phosphorylates penciclovir to a monophosphate form that, in turn, is converted by cellular kinases to the active form penciclovir triphosphate. Biochemical studies demonstrate that penciclovir triphosphate inhibits HSV DNA polymerase competitively with deoxyguanosine triphosphate. Consequently, α-herpes viral DNA synthesis and, therefore, replication are selectively inhibited. Penciclovir triphosphate has an intracellular half-life of 10 hours in HSV-1 and 20 hours in HSV-2 infected cells grown in culture. However, the clinical significance of the intracellular half-life is unknown.
How supplied
16 HOW SUPPLIED/STORAGE AND HANDLING DENAVIR is supplied in a 5 gram tube containing 10 mg of penciclovir per gram in a cream base, which is equivalent to 1% (w/w). The white cream is available as follows: NDC 0378-9720-55 carton containing one 5 gram tube Store at 20º to 25ºC (68º to 77ºF). [See USP Controlled Room Temperature].
Patient information
Administration Instructions Advise the patient that treatment should be started at the earliest sign of a cold sore (i.e. tingling, redness, itching, or bump). Inform the patient to apply the cream every 2 hours during waking hours for 4 days and to wash their hands with soap and water after using DENAVIR. Denavir is a registered trademark of Denco Asset, LLC, a Mylan Company. The brands listed are trademarks of their respective owners. ©2018 Mylan Pharmaceuticals Inc. Manufactured for: Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A. Manufactured by: Confab Laboratories Inc. St-Hubert, Canada J3Y 3X3 Revised: 11/2018 301459-03 CON:PENCCR:R2
Label text from the FDA structured product label by Mylan Pharmaceuticals Inc. (revised Nov 26, 2018). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Penciclovir in 1 product
Denavir NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 0378-9720 | Penciclovir 10 mg/g Cream | Mylan Pharmaceuticals Inc. | NDA |
Frequently asked questions
What is Denavir used for?
1 INDICATIONS AND USAGE DENAVIR is a deoxynucleoside analog HSV DNA polymerase inhibitor indicated for the treatment of recurrent herpes labialis (cold sores) in adults and children 12 years of age or older. DENAVIR ® is a deoxynucleoside analog HSV DNA polymerase inhibitor indicated for the treatment of recurrent herpes labialis (cold sores) in adults and pediatric patients12 years of age and…
What are the side effects of Denavir?
• One or more local skin reactions were reported by 3% of the subjects treated with DENAVIR and 4% of placebo-treated patients. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed… See the full label for the complete list.
Who makes Denavir?
Denavir is listed by 1 labeler in the FDA NDC directory, including Mylan Pharmaceuticals Inc..