Fenivir

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Fenivir uses

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Fenivir reviews

1 INDICATIONS AND USAGE

Fenivir is a nucleoside 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.

Fenivir^® is a nucleoside analog HSV DNA polymerase inhibitor indicated for:

• The treatment of recurrent herpes labialis (cold sores) in adults and children 12 years of age and older (1)

2 DOSAGE AND ADMINISTRATION

Fenivir should be applied every 2 hours during waking hours for a period of 4 days. Treatment should be started as early as possible (i.e., during the prodrome or when lesions appear).

• Fenivir should be applied every 2 hours during waking hours for a period of 4 days (2).
  

• Treatment should be started as early as possible (i.e., during the prodrome or when lesions appear) (2).

3 DOSAGE FORMS AND STRENGTHS

Each gram of Fenivir contains 10 mg of Fenivir in a cream base, which is equivalent to 1% (w/w).

• Topical cream containing 1% Fenivir (3).

4 CONTRAINDICATIONS

Fenivir is contraindicated in patients with known hypersensitivity to the product or any of its components.

• In patients with known hypersensitivity to the product or any of its components (4).

5 WARNINGS AND PRECAUTIONS

• Only for topical use of herpes labialis on the lips and face.

5.1 General

Fenivir 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 Fenivir has not been established in immunocompromised patients.

6 ADVERSE REACTIONS

• One or more local skin reactions were reported by 3% of the patients treated with Fenivir and 4% of placebo-treated patients.

To report SUSPECTED ADVERSE REACTIONS, contact Prestium Pharma, Inc. at 1-866-897-5002 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, 1516 patients were treated with Fenivir (penciclovir cream) and 1541 with placebo. One or more local adverse reactions were reported by 3% of the patients treated with Fenivir and 4% of placebo-treated patients. The rates of reported local adverse reactions are shown in Table 1.

	Fenivir n=1516 %	Placebo N=1541 %
Applications site reaction Hypesthesia/Local anesthesia Taste perversion Rash (erythematous)	1 <1 <1 <1	2 <1 <1 <1

Two studies, enrolling 108 healthy subjects, were conducted to evaluate the dermal tolerance of 5% Fenivir cream (a 5-fold higher concentration than the commercial formulation) compared to vehicle using repeated occluded patch testing methodology. The 5% Fenivir 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 Fenivir. 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 Fenivir 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 Fenivir.

General: Headache, oral/pharyngeal edema, parosmia.

Skin: Aggravated condition, decreased therapeutic response, local edema, pain, paresthesia, pruritus, skin discoloration, and urticaria.

7 DRUG INTERACTIONS

No drug interaction studies have been performed with Fenivir. Due to minimal systemic absorption of Fenivir, systemic drug interactions are unlikely.

No drug interaction studies have been performed with Fenivir. Due to minimal systemic absorption of Fenivir, systemic drug interactions are unlikely (7).

8 USE IN SPECIFIC POPULATIONS

• Pregnancy Category B

8.1 Pregnancy

Category B

There are no adequate and well-controlled studies in pregnant women.

Animal Data

No adverse effects on the course and outcome of pregnancy or on fetal development were noted in rats and rabbits following the intravenous administration of Fenivir at doses of 80 and 60 mg/kg/day, respectively (estimated human equivalent doses of 13 and 18 mg/kg/day for the rat and rabbit, respectively, based on body surface area conversion; the body surface area doses being 260 and 355x the maximum recommended dose following topical application of the Fenivir cream). Because animal reproduction studies are not always predictive of human response, Fenivir should be used during pregnancy only if clearly needed.

8.3 Nursing Mothers

There is no information on whether Fenivir is excreted in human milk after topical administration. However, following oral administration of famciclovir to lactating rats, Fenivir was excreted in breast milk at concentrations higher than those seen in the plasma. Therefore, a decision should be made whether to discontinue the drug, taking into account the importance of the drug to the mother.

There are no data on the safety of Fenivir in newborns.

8.4 Pediatric Use

An open-label, uncontrolled trial with Fenivir cream 1% was conducted in 102 patients, 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 patients ≥ 65 years of age, the adverse events profile was comparable to that observed in younger patients.

10 OVERDOSAGE

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

11 DESCRIPTION

Fenivir (penciclovir) cream 1% contains Fenivir, an antiviral agent active against herpes viruses. Fenivir is available for topical administration as a 1% white cream. Each gram of Fenivir contains 10 mg of Fenivir and the following inactive ingredients: cetostearyl alcohol, mineral oil, polyoxyl 20 cetostearyl ether, propylene glycol, purified water and white petrolatum.

Chemically, Fenivir 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:

Fenivir 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. Fenivir is not hygroscopic. Its partition coefficient in n-octanol/water at pH 7.5 is 0.024 (logP = -1.62).

Figure 1: Structural Formula of Fenivir

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Fenivir is an antiviral agent active against herpes viruses [see Microbiology ].

12.3 Pharmacokinetics

Measurable Fenivir concentrations were not detected in plasma or urine of healthy male volunteers (n=12) following single or repeat application of the 1% cream at a dose of 180 mg Fenivir daily (approximately 67 times the estimated usual clinical dose).

Pediatric Patients: The systemic absorption of Fenivir following topical administration has not been evaluated in patients < 18 years of age.

12.4 Microbiology

Mechanism of Action : The antiviral compound Fenivir 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 Fenivir to a monophosphate form that, in turn, is converted by cellular kinases to the active form Fenivir triphosphate. Biochemical studies demonstrate that Fenivir triphosphate inhibits HSV polymerase competitively with deoxyguanosine triphosphate. Consequently, herpes viral DNA synthesis and, therefore, replication are selectively inhibited. Fenivir 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.

Antiviral Activity: In cell culture studies, Fenivir has antiviral activity against the following herpes viruses: HSV-1 and HSV-2. The antiviral activity of Fenivir against wild type strains grown on human foreskin fibroblasts was assessed with a plaque reduction assay and staining with crystal violet 3 days postinfection for HSV. The median EC₅₀ values of Fenivir against laboratory and clinical isolates of HSV-1 and HSV-2 were 2 µM (range 1.2 to 2.4 µM, n=7) and 2.6 µM (range 1.6 to 11 µM, n=6), respectively.

Resistance : Penciclovir-resistant mutants of HSV can result from mutations in viral thymidine kinase (TK) and DNA polymerase genes. Mutations in the viral TK gene may lead to complete loss of TK activity (TK negative), reduced levels of TK activity (TK partial), or alteration in the ability of viral TK to phosphorylate the drug without an equivalent loss in the ability to phosphorylate thymidine (TK altered). The median EC₅₀ values observed in a plaque reduction assays with Fenivir resistant HSV-1 and HSV-2 were 69 µM (range 14 to 115 µM, n=6) and 46 µM (range 4 to > 395 µM, n=9), respectively. The possibility of viral resistance to Fenivir should be considered in patients who fail to respond or experience recurrent viral shedding during therapy.

Cross-resistance : Cross-resistance has been observed among HSV DNA polymerase inhibitors. The most commonly encountered acyclovir-resistant mutants that are deficient in viral thymidine kinase (TK negative) are also resistant to Fenivir.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

In clinical trials, systemic drug exposure following topical administration of Fenivir cream was negligible, as the Fenivir 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 Fenivir from the topically applied product has been used. Based on the use of the maximal recommended topical dose of Fenivir of 0.05 mg/kg/day and an assumption of 100% absorption, the maximum theoretical plasma AUC_{0-24 hrs} for Fenivir is approximately 0.129 mcg.hr/mL.

Carcinogenesis: Two-year carcinogenicity studies were conducted with famciclovir (the oral prodrug of Fenivir) 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 Fenivir 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 Fenivir), or in male and female mice at doses up to 600 mg/kg/day (approximately 100x the maximum theoretical human AUC for Fenivir).

Mutagenesis: When tested in vitro, Fenivir 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 Fenivir 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, Fenivir 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 Fenivir (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 Fenivir. 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 Fenivir 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).

14 CLINICAL STUDIES

Fenivir was studied in two double-blind, placebo (vehicle)-controlled trials for the treatment of recurrent herpes labialis in which otherwise healthy adults were randomized to either Fenivir or placebo. Therapy was to be initiated by the subjects within 1 hour of noticing signs or symptoms and continued for 4 days, with application of study medication every 2 hours while awake. In both studies, the mean duration of lesions was approximately one-half-day shorter in the subjects treated with Fenivir (N=1,516) as compared to subjects treated with placebo (N=1,541) (approximately 4.5 days versus 5 days, respectively). The mean duration of lesion pain was also approximately one half-day shorter in the Fenivir group compared to the placebo group.

16 HOW SUPPLIED/STORAGE AND HANDLING

Fenivir is supplied in a 1.5 gram and 5 gram tube containing 10 mg of Fenivir per gram.

NDC 50816-624-01

NDC 40076-624-05

Store at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted to 15ºC to 30ºC (59ºF to 86ºF).

17 PATIENT COUNSELING INFORMATION

17.1 General

Fenivir is a prescription topical cream for the treatment of cold sores that occur on the face and lips. It is not a cure for cold sores and not all patients respond to it. Do not use if you are allergic to Fenivir (penciclovir) or any of the ingredients in Fenivir. Before you use Fenivir, tell your doctor if you are pregnant, planning to become pregnant, or are breast-feeding.

17.2 Instructions for Use

Wash your hands. Your face should be clean and dry. Apply a layer of Fenivir to cover only the cold sore area or the area of tingling (or other symptoms) before the cold sore appears. Rub in the cream until it disappears. Apply the cream every 2 hours during waking hours for 4 days. Treatment should be started at the earliest sign of a cold sore (i.e. tingling, redness, itching, or bump). Wash your hands with soap and water after using Fenivir. Store Fenivir at room temperature between 68°F to 77°F (20ºC to 25ºC). Keep out of reach of children.

17.3 Possible Side Effects

Fenivir was well tolerated in clinical studies in patients with cold sores. Common skin-related side effects that occurred when Fenivir was applied are application site reactions, local anesthesia, and rash. Taste perversion was also reported.

September 2013

Manufactured for Prestium Pharma , Inc.

Newtown, PA 18940

by Novartis Pharma GmbH, Wehr, Germany

Dena v ir ® is licensed to Prestium Pharma, Inc. from Denco Asset, LLC.

©201 3 Prestium Pharma, Inc.

NDC 40076-624-05

Fenivir ®

( Fenivir cream) 1%

5 g (Net Wt.)

For Topical Use Only

PRINCIPAL DISPLAY PANEL NDC 40076-624-05 Denavir® (penciclovir cream) 1% 5 g (Net Wt.) For Topical Use Only

Fenivir pharmaceutical active ingredients containing related brand and generic drugs:

• Penciclovir

Fenivir available forms, composition, doses:

• Cream; Topical; Penciclovir 1%

Fenivir destination | category:

• Human:
• Antivirals

Fenivir Anatomical Therapeutic Chemical codes:

• D06BB06 - Penciclovir
• J05AB13 - Penciclovir

Fenivir pharmaceutical companies:

• Novartis

References

1. Dailymed."DENAVIR (PENCICLOVIR) CREAM [PRESTIUM PHARMA, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
2. Dailymed."PENCICLOVIR: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
3. "penciclovir". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Fenivir?

Depending on the reaction of the Fenivir after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Fenivir not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Fenivir addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

Review

sdrugs.com conducted a study on Fenivir, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Fenivir consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

Visitor reports

Visitor reviews

Admin	19 Sep 2017 12:12
	Hello Johnny, The active ingredient is Penciclovir.
Johnny	19 Sep 2017 10:54
	No review, just a question. What are the ingredients for Fenivir ?

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The information was verified by Dr. Rachana Salvi, MD Pharmacology