ACYCLOVIR, ACYCLOVIR SODIUM

ACYCLOVIR, ACYCLOVIR SODIUM (ay-sye'kloe-ver) Zovirax Classifications: antiviral; Therapeutic: antiviral Pregnancy Category: B

Availability

200 mg capsules; 400 mg, 800 mg tablets; 200 mg/5 mL suspension; 50 mg/mL injection; 5% ointment, cream

Action

Acyclovir is a synthetic nucleoside analog of guanine. Acyclovir preferentially interferes with DNA synthesis of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) and varicella-zoster virus, thereby inhibiting viral replication.

Therapeutic Effect

Acyclovir reduces viral shedding and formation of new lesions and speeds healing time. It demonstrates antiviral activity against herpes virus simiae (B virus), Epstein-Barr (infectious mononucleosis), varicella-zoster and cytomegalovirus, but does not eradicate the latent herpes virus.

Uses

Parenterally for treatment of initial and recurrent mucosal and cutaneous herpes simplex virus (HSV-1 and HSV-2) infections in immunocompromised adults and children and for severe initial episodes of herpes genitalis in immunocompetent (normal immune system) patients. Treatment of herpes encephalitis or neonatal herpes infection. Used orally for treatment of initial episodes of genital herpes, for management of selected patients with severe recurrent episodes, and for prophylaxis to reduce frequency and severity of recurrent infections. Used topically for herpes labialis (cold sores), initial episodes of herpes genitalis and in non-life-threatening mucocutaneous herpes simplex virus infections in immunocompromised patients.

Unlabeled Uses

Treatment of eczema herpeticum caused by HSV localized and disseminated herpes zoster. Prevention of CMV in transplant patients. Prevention of HSV in immunosuppressed HSV-seropositive patients.

Contraindications

Hypersensitivity to acyclovir and valacyclovir.

Cautious Use

Renal insufficiency, dehydration, seizure disorders, or neurologic disease; pregnancy (category B).

Route & Dosage

Cold Sores Adult/Adolescents (≥12 y): Topical Apply 5 times/d for 4 d Genital Herpes Simplex Adult: PO 400 mg t.i.d. for 7–10 d cycle IV 5 mg/kg q8h x 7 d Topical Apply q3h 6 times/d for 7 d Child (<12 y): IV 250 mg/m2 q8h, 80 mg/kg/d in 2–5 doses Herpes Simplex Immunocompromised Patient Adult: IV 5 mg/kg q8h x 7 d Child: IV 10 mg/kg q8h x 7 d Prophylaxis for Genital Herpes Simplex Adult: PO 200 mg 2–5 times/d, 400 mg t.i.d., 800 mg b.i.d. Child: PO 80 mg/kg/d in 2–5 divided doses Severe Genital Herpes Adult/Adolescent: IV 5 mg/kg q8h x 5 d Herpes Zoster Adult: PO 800 mg q4h 5 times/d Child: PO 80 mg/kg/d in 5 divided doses Herpes Simplex Encephalitis Adult: IV 10 mg/kg q8h x 10 d Child (3 mo–12 y): IV 20 mg/kg q8h x 10 d Neonate (<3 mo): IV 10 mg/kg q8h x 10 d Varicella Zoster Child/Adolescent: PO 20 mg/kg (max: 800 mg) q.i.d. for 5 d cycle initiated within 24 h of onset of rash Adult: IV 10 mg/kg q8h x 7 d Child: IV 20 mg/kg q8h x 7 d Obesity Patient dose should be calculated using IBW. Renal Impairment Clcr 25–50 mL/min: standard dose q12h; 10–25 mL/min: standard dose q24h; <10 mL/min give half normal dose q24h Hemodialysis: Administer dose after dialysis

Administration

Oral

• Shake suspension well prior to use.
• Store capsules in tight, light-resistant containers at 15°–30° C (59°–86° F) unless otherwise directed.

Topical

• Wash hands thoroughly before and after treatment of lesions and after handling and disposition of secretions.
• Apply approximately ? inch of cream or ointment ribbon for each 4 square inches of surface area. Use sufficient ointment or cream to completely cover lesions.
• Apply topical preparation with finger cot or surgical glove.
• Store at 15°–25° C (59°–78° F) unless otherwise directed.

Intravenous PREPARE: Intermittent: • Reconstitute by adding 10 mL sterile water for injection to 500-mg vial to yield 50 mg/mL. Note: Do not use bacteriostatic water for injection containing benzyl alcohol. Shake well.• Use reconstituted solution within 12 h.• Further dilute to ≤7 mg/mL to reduce risk of renal injury and phlebitis. Example: Add 1 mL of reconstituted solution to 9 mL of diluent to yield 5 mg/mL.• Use standard electrolyte and glucose solutions (e.g., NS, RL, D5W) for dilution. Diluted solution should be used within 24 h.  ADMINISTER: Intermittent: • Administer over at least 1 h to prevent renal tubular damage. Rapid or bolus IV administration must be avoided.• Monitor IV flow rate carefully; infusion pump or microdrip infusion set preferred.  INCOMPATIBILITIES Solution/additive: Bacteriostatic water for injection, dobutamine, dopamine, pantoprazole. Y-site: Amifostine, amsacrine, aztreonam, cefepime, dobutamine, dopamine, fludarabine, foscarnet, gemcitabine, idarubicin, levofloxacin, ondanseteron, piperacillin/tazobactam, sargramostim, TPN, vinorelbine.

• Refrigerated reconstituted solution may precipitate; however, crystals will redissolve at room temperature.
• Store acyclovir powder and reconstituted solutions at controlled room temperature preferably at 15°–30° C (59°–86° F) unless otherwise directed by manufacturer.

Adverse Effects (≥1%)

Body as a Whole: Generally minimal and infrequent. CNS: Headache, light-headedness, lethargy, fatigue, tremors, confusion, seizures, dizziness. GI: Nausea, vomiting, diarrhea. Urogenital: Glomerulonephritis, renal tubular damage, acute renal failure. Skin: Rash, urticaria, pruritus, burning, stinging sensation, irritation, sensitization. Other: Inflammation or phlebitis at IV injection site, sloughing (with extravasation), thrombocytopenic purpura/hemolytic uremic syndrome.

Interactions

Drug: Probenecid decreases acyclovir elimination; zidovudine may cause increased drowsiness and lethargy.

Pharmacokinetics

Absorption: Oral dose is 15–30% absorbed. Peak: 1.5–2 h after oral dose. Distribution: Into most tissues with lower levels in the CNS; crosses placenta. Metabolism: Drug is primarily excreted unchanged. Elimination: Renally eliminated; also excreted in breast milk. Half-Life: 2.5–5 h.

Nursing Implications

Assessment & Drug Effects

• Observe infusion site during infusion and for a few days following infusion for signs of tissue damage.
• Monitor I&O and hydration status. Keep patient adequately hydrated during first 2 h after infusion to maintain sufficient urinary flow and thus prevent precipitation of drug in renal tubules. Consult physician about amount and length of time oral fluids need to be pushed after IV drug treatment.
• Monitor for S&S of: reinfection in pregnant patients; acyclovir-induced neurologic symptoms in patients with history of neurologic problems; drug resistance in immunocompromised patients receiving prolonged or repeated therapy; acute renal failure with concomitant use with other nephrotoxic drugs or preexisting renal disease.
• Lab tests: Monitor baseline and periodic renal function studies, particularly with IV administration. Elevations of BUN and serum creatinine and decreases in creatinine clearance indicate need for dosage adjustment, discontinuation of drug, or correction of fluid and electrolyte balance.
• Monitor for adverse effects and viral resistance with long-term prophylactic use of the oral drug.

Patient & Family Education

• Start therapy as soon as possible after onset of S&S for best results.
• Do not exceed recommended dosage, frequency of drug administration, or specified duration of therapy. Contact physician if relief is not obtained or adverse effects appear.
• Cleanse affected areas with soap and water 3–4 times daily prior to topical application; dry well before application. With application to genitals, wear loose-fitting clothes over affected areas.
• Note: Even after HSV infection is controlled, latent virus can be activated by stress, trauma, fever, exposure to sunlight, sexual intercourse, menstruation, treatment with immunosuppressive drugs.
• Refrain from sexual intercourse if either partner has S&S of herpes infection; neither topical nor systemic drug prevents transmission to other individuals.
• Avoid topical drug contact in or around eyes. Report unexplained eye symptoms to physician immediately (e.g., redness, pain); untreated infection can lead to corneal keratitis and blindness.

---

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug