Penciclovir

Class: Antivirals
VA Class: DE103
Molecular Formula: C10H15N5O3
CAS Number: 39809-25-1
Brands: Denavir

Introduction

Antiviral; acyclic purine nucleoside analog of guanine.1 2 3 5 9 10 11 12 14

Uses for Penciclovir

Herpes Labialis

Treatment of recurrent herpes labialis (oral and perioral herpes, cold sores, fever blisters) in adults.1 2 6 7 8 20

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Efficacy not established in immunocompromised patients or children.1 20

Penciclovir Dosage and Administration

Administration

Topical Administration

Appy topically to lesions of the lips and surrounding skin as a 1% cream.1 2 7 12 21

Do not apply in or near the eyes since irritation may occur.1 Application to mucous membranes not recommended.1

Dosage

Adults

Herpes Labialis
Topical

Rub 1% cream gently into the affected area every 2 hours while awake (about 9, but at least 6, times daily) for 4 days.1 2 12 Use sufficient quantity to adequately cover all lesions of the lips and surrounding skin.21

Initiate at the earliest sign or symptom (i.e., within 1 hour of the prodrome or appearance of the first lesion) of herpes labialis.1 2 12

Cautions for Penciclovir

Contraindications

  • Hypersensitivity to penciclovir or any ingredient in the formulation.1

Warnings/Precautions

Specific Populations

Pregnancy

Category B.1

Lactation

Not known whether distributed into human milk after topical application.1 Penciclovir is distributed into milk in rats following oral administration of famciclovir (the oral prodrug of penciclovir).1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established in children <18 years of age.1

Geriatric Use

Adverse effects profile in adults ≥65 years of age is similar to that in younger adults.1

Common Adverse Effects

Headache.1

Penciclovir Pharmacokinetics

Absorption

Bioavailability

Not appreciably absorbed into systemic circulation following topical application to the skin.1 2 5 7 12

Not detected in plasma or urine of adults following single or repeated application of 1% penciclovir cream at a dosage of 180 mg daily (about 67 times the estimated usual topical dosage).1 2 5 7 12 Systemic absorption not evaluated in children <18 years of age.1

Elimination

Metabolism

Converted in vivo to the pharmacologically active triphosphate metabolite.1 2 5 7 9 10 11 12 13 14

Stability

Storage

Topical

Cream

20°–25°C.1

Actions and Spectrum

  • Converted in vivo to the pharmacologically active triphosphate metabolite.1 2 5 7 9 10 11 12 13 14

  • Exerts its antiviral effect by interfering with DNA synthesis and inhibiting viral replication.1 2 3 9 12

  • Active against various Herpesviridae,1 2 5 7 9 10 11 12 13 14 including herpes simplex virus types 1 and 2 (HSV-1 and HSV-2),1 2 3 5 10 12 14 varicella-zoster virus (VZV),2 5 10 12 13 14 and Epstein-Barr virus (EBV).5 9 10 11 Only limited activity in vitro against cytomegalovirus (CMV).5 11

  • In vitro, penciclovir triphosphate is 10–20 times more stable than acyclovir triphosphate within HSV-infected cells, resulting in more prolonged antiviral activity.2 5 8 9 14

  • Resistance to penciclovir reported in HSV and VZV.1 4 5 8 12 14 15

  • Most (but not all) acyclovir-resistant HSV and VZV are cross-resistant to penciclovir.1 4 5 8 12 13 14 15

Advice to Patients

  • Importance of avoiding contact with eyes.1 If contact with the eye(s) occurs, the affected eye(s) should be washed with large amounts of water; patients should consult a clinician if ocular irritation persists.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.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. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Penciclovir

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Topical

Cream

1%

Denavir (with propylene glycol)

Novartis

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Denavir 1% Cream (NEW AMERICAN THERAPEUTICS): 5/$179.99 or 15/$505.95

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 1, 2005. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Novartis. Denavir (penciclovir) topical cream 1% prescribing information. East Hanover, NJ; 2001 Jan.

2. Spruance SL, Rea TL, Thoming C et al. Penciclovir cream for the treatment of herpes simplex labialis. JAMA. 1997; 277:1374-79. [IDIS 384117] [PubMed 9134943]

3. Wiltink EH. New promising antiviral drugs. Drugs of Today. 1995; 31:273-82.

4. Chatis PA, Crumpacker CS. Resistance of herpesviruses to antiviral drugs. Antimicrob Agents Chemother. 1992; 36:1589-95. [IDIS 299816] [PubMed 1416838]

5. Alrabiah FA, Sacks SL. New antiherpesvirus agents. Drugs. 1996; 52:17-32. [PubMed 8799682]

6. Ackerman B (SmithKline Beecham, Philadelphia, PA): Personal communication; 1997 July 10.

7. Raborn GW for the Penciclovir Topical Collaborative Study Group. Penciclovir cream for recurrent herpes simplex labialis: an effective new treatment. Proceedings of ICAAC New Orleans 1996. Abstract No. H81.

8. Boyd MR, Safrin S, Kern ER. Penciclovir: a review of its spectrum of activity, selectivity and cross-resistance patterns. Antiviral Chem Chemother. 1993; 4(Suppl 1): 3-11.

9. Bacon TH, Boyd MR. Activity of penciclovir against Epstein-Barr virus. Antimicrob Agents Chemother. 1995; 39:1599-1602. [IDIS 350501] [PubMed 7492112]

10. Gnann JW Jr. New antivirals with activity against varicella-zoster virus. Ann Neurol. 1994; 34:S69-72.

11. Kulikowski T. Structure-activity relationships and conformational features of antiherpetic pyrimidine and purine nucleoside analogues: a review. Pharm World Sci. 1994; 16:127-138. [IDIS 331981] [PubMed 8032338]

12. Anon. Topical penciclovir for herpes labialis. Med Lett Drugs Ther. 1997; 39:57-8. [PubMed 9205430]

13. Hasegawa T, Kurokawa M, Yukawa TA et al. Inhibitory action of acyclovir (ACV) and penciclovir (PCV) on plaque formation and partial cross-resistance of ACV-resistant varicella-zoster virus to PCV. Antiviral Res. 1995; 27:271-9. [PubMed 8540749]

14. Safrin S, Phan L. In vitro activity of penciclovir against clinical isolates of acyclovir-resistant and foscarnet-resistant herpes simplex virus. Antimicrob Agents Chemother. 1993; 37:2241-3. [IDIS 320621] [PubMed 8257152]

15. Talarico CL, Phelps WC, Biron KK. Analysis of the thymidine kinase genes from acyclovir-resistant mutants of varicella-zoster virus isolated from patients with AIDS. J Virol. 1993; 67:1024-33. [PubMed 8380452]

16. Centers for Disease Control and Prevention. 1993 Sexually transmitted diseases guidelines. 1993; 42(Suppl RR-14):22-5.

17. Shaw M, King M, Best JM et al. Failure of acyclovir cream in treatment of recurrent herpes labialis. BMJ. 1985; 291:7-9. [IDIS 202407] [PubMed 3926067]

18. Spruance SL, Crumpacker CS, Schnipper LE et al. Early, patient-initiated treatment of herpes labialis with topical 10% acyclovir. Antimicrob Agents Chemother. 1984; 25: 553-5. [IDIS 185372] [PubMed 6732224]

19. Spruance SL, Schnipper LE, Overall JC et al. Treatment of herpes simplex labialis with topical acyclovir in polyethylene glycol. J Infect Dis. 1982; 146:85-90. [IDIS 153489] [PubMed 7045255]

20. FDA summary basis of approval.

21. SmithKline Beecham, Philadelphia, PA: Personal communication.

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