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Acyclovir (Topical)


General


Pronunciation

(ay SYE kloe veer)


Brand Names: U.S.

  • Sitavig
  • Zovirax

Indications


Use: Labeled Indications

Herpes virus:

Buccal tablet: Treatment of recurrent herpes labialis (cold sores) in immunocompetent adults.

Cream: Treatment of recurrent herpes labialis (cold sores) in immunocompetent children ≥12 years of age, adolescents, and adults.

Ointment: Management of initial genital herpes and in limited non-life-threatening mucocutaneous herpes simplex virus infections in immunocompromised patients.


Contraindications


Buccal tablet: Hypersensitivity to acyclovir, valacyclovir, milk protein concentrate or any component of the formulation

Cream, ointment: Hypersensitivity to acyclovir, valacyclovir, or any component of the formulation


Dosing and Administration


Dosing: Adult

Genital HSV: Topical ointment: Initial episode: 1/2 "  ribbon of ointment for a 4 "  square surface area every 3 hours (6 times daily) for 7 days

Herpes labialis (cold sores):

Topical cream: Apply 5 times daily for 4 days

Buccal tablet: Apply one 50 mg tablet as a single dose to the upper gum region (canine fossa).

Mucocutaneous HSV (non-life-threatening, immunocompromised): Topical ointment: 1/2 "  ribbon of ointment for a 4 "  square surface area every 3 hours (6 times daily) for 7 days


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Herpes labialis (cold sores): Children ≥12 years and Adolescents: Topical cream: Refer to adult dosing.


Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer 's labeling. However, dosage adjustment is unlikely due to low systemic absorption.


Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer 's labeling. However, dosage adjustment is unlikely due to low systemic absorption.


Administration

Oral: Buccal tablet: Apply within 1 hour after onset of prodromal symptoms and before appearance of any signs of lesions. Apply tablet with a dry finger immediately after removing it from packaging blister. Place tablets to the upper gum just above the incisor tooth (canine fossa) on the same side of the mouth as the prodromal symptoms and hold in place with slight pressure over the upper lip for 30 seconds to ensure adhesion. The rounded side of the tablet should be placed on the upper gum (for comfort purposes, does not affect efficacy). Do not crush, chew, suck, or swallow. If tablet falls off within the first 6 hours, reposition the same tablet immediately or apply a new tablet. If tablet is swallowed within the first 6 hours, drink a glass of water and apply a new tablet. If tablet falls out or is swallowed after the first 6 hours, do not reapply. Patients may eat and drink normally while tablet is in place. Avoid gum chewing, brushing teeth, wearing an upper denture or touching/pressing the tablet after placement. Rinse mouth gently if teeth need to be cleaned while the tablet is in place. Drink plenty of liquids in case of dry mouth.

Topical: Cream or ointment: Apply as early as possible following the onset of prodromal symptoms or when lesions appear.

Cream: Not for use on the genitals. Ensure the face and/or lips are clean and dry. Not for use in the eye, mouth or mucous membranes. Wash hands with soap and water prior to application and after application. Apply an amount to sufficiently cover the affected area, including the outer margin. Avoid unnecessary rubbing of the affected area. Do not apply other topical products to the affected area during therapy.

Ointment: Not for use in the eye. Apply using a finger cot or rubber glove to avoid transmission to other parts of the body or to other persons.


Storage

Buccal tablet: Store at 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F); excursions permitted between 15 ‚ °C and 30 ‚ °C (59 ‚ °F and 86 ‚ °F). Protect from moisture.

Cream: Store at or below 25 ‚ °C (77 ‚ °F); excursions permitted between 15 ‚ °C and 30 ‚ °C (59 ‚ °F and 86 ‚ °F).

Ointment: Store at controlled room temperature of 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F) in a dry place.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Cream, External:

Zovirax: 5% (2 g [DSC], 5 g) [contains cetostearyl alcohol, propylene glycol]

Ointment, External:

Zovirax: 5% (30 g)

Generic: 5% (5 g, 15 g, 30 g)

Tablet, Buccal:

Sitavig: 50 mg [contains milk protein concentrate]


Drug Interactions

Talimogene Laherparepvec: Antiherpetic Antivirals may diminish the therapeutic effect of Talimogene Laherparepvec. Monitor therapy


Adverse Reactions


>10%: Dermatologic: Local pain (ointment 30%; mild; includes transient burning and stinging)

1% to 10%:

Central nervous system: Lethargy (buccal tablet 1%)

Dermatologic: Erythema (buccal tablet 1%), skin rash (buccal tablet 1%)

Gastrointestinal: Aphthous stomatitis (buccal tablet 1%), gingival pain (buccal tablet 1%)

Local: Application site reaction (cream 5%; including dry lips, desquamation, dryness of skin, cracked lips, burning skin, pruritus, flakiness of skin, and stinging on skin); application site irritation (buccal tablet 1%)

<1% (Limited to important or life-threatening): Anaphylaxis, eczema


Warnings/Precautions


Concerns related to adverse effects:

- Dermatologic toxicity: Cream may be irritating and cause contact sensitization. The sensitizing ingredient has not been identified.

Disease-related concerns:

- Appropriate use: Genital herpes: Physical contact should be avoided when lesions are present; transmission may also occur in the absence of symptoms. Treatment should begin with the first signs or symptoms. There are no data to support the use of acyclovir ointment to prevent transmission of infection to other persons or prevent recurrent infections if no signs or symptoms are present.

- Appropriate use: Herpes labialis: Treatment should begin with the first signs or symptoms.

Special populations:

- Immunocompromised patients: Buccal tablet, cream: Use and safety has not been studied; use with caution.

Dosage form specific issues:

- Buccal tablet: Apply to the area of the upper gum above the incisor tooth on the same side as the symptoms; do not apply to the inside of the lip or cheek.

- Cream: For external use only to the lips and face; do not apply to eye or inside the mouth or nose, or to any mucous membranes.

- Ingredient precaution: Some products may contain milk protein concentrate.

- Ointment: For cutaneous use only; do not use in the eye.


Pregnancy Risk Factor

B


Pregnancy Considerations

Teratogenic effects were not observed in animal studies. When administered orally, acyclovir crosses the placenta. Refer to the Acyclovir (Systemic) monograph for details. The amount of acyclovir available systemically following topical application of the cream or ointment is significantly less in comparison to oral doses.


Actions


Pharmacology

Acyclovir is converted to acyclovir monophosphate by virus-specific thymidine kinase then further converted to acyclovir triphosphate by other cellular enzymes. Acyclovir triphosphate inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and being incorporated into viral DNA.


Absorption

Topical: Plasma concentrations following topical application of the cream were below the limit of detection in 5/6 male volunteers (<0.01 Ž žM) and 0.014 Ž žM in one subject. Following application of the ointment to patients with varicella-zoster infection, acyclovir plasma concentrations were <0.01 to 0.28 mcg/mL in patients with normal renal function and <0.01 to 0.78 mcg/mL in a patient with renal impairment.

Buccal tablet: Single dose application of buccal tablets containing 50 mg of acyclovir to the buccal mucosa provided mean maximum salivary concentrations 8 hours after tablet application. Plasma concentrations were delayed (undetectable at 5 hours) and subsequently below antiviral activity concentration (0.018 to 0.055 mcg/mL).


Excretion

Urine (Buccal tablet: Primarily renally excreted unchanged; Cream: 0.04% of the daily dose; Ointment: <0.02% to 9.4% of the daily dose)


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience burning, stinging, dry skin, itching, dry lips, application site pain, or headache. Have patient report immediately to prescriber severe application site irritation (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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