Acyclovir

U.S. BRAND NAMES — Zovirax®
PHARMACOLOGIC CATEGORY Antiviral Agent
DOSING: ADULTS — Note: Obese patients should be dosed using ideal body weight
Genital HSV: I.V.: Immunocompetent: Initial episode, severe: 5 mg/kg every 8 hours for 5-7 days Oral: Initial episode: 200 mg every 4 hours while awake (5 times/day) for 10 days (per manufacturer's labeling); 400 mg 3 times/day for 5-10 days has also been reported Recurrence: 200 mg every 4 hours while awake (5 times/day) for 5 days (per manufacturer's labeling; begin at earliest signs of disease); 400 mg 3 times/day for 5 days has also been reported Chronic suppression: 400 mg twice daily or 200 mg 3-5 times/day, for up to 12 months followed by re-evaluation (per manufacturer's labeling); 400-1200 mg/day in 2-3 divided doses has also been reported Topical: Immunocompromised: Ointment: Initial episode: 1/2" ribbon of ointment for a 4" square surface area every 3 hours (6 times/day) for 7 days
Herpes labialis (cold sores): Topical: Apply 5 times/day for 4 days
Herpes zoster (shingles): Oral: Immunocompetent: 800 mg every 4 hours (5 times/day) for 7-10 days I.V.: Immunocompromised: 10 mg/kg/dose or 500 mg/m2/dose every 8 hours for 7 days
HSV encephalitis: I.V.: 10 mg/kg/dose every 8 hours for 10 days (per manufacturer's labeling); 10-15 mg/kg/dose every 8 hours for 14-21 days also reported
Mucocutaneous HSV: I.V.: Immunocompromised: 5 mg/kg/dose every 8 hours for 7 days (per manufacturer's labeling); dosing for up to 14 days also reported Oral: Immunocompromised (unlabeled use): 400 mg 5 times a day for 7-14 days Topical: Ointment: Nonlife-threatening, immunocompromised: 1/2" ribbon of ointment for a 4" square surface area every 3 hours (6 times/day) for 7 days
Varicella-zoster (chickenpox): Begin treatment within the first 24 hours of rash onset: Oral: >40 kg (immunocompetent): 800 mg/dose 4 times a day for 5 days I.V.: Immunocompromised (unlabeled use): 1500 mg/m2/day divided every 8 hours or 10 mg/kg/dose every 8 hours for 7-10 days
Prevention of HSV reactivation in HIV-positive patients, for use only when recurrences are frequent or severe (unlabeled use): Oral: 200 mg 3 times/day or 400 mg 2 times/day
Prevention of HSV reactivation in HSCT (unlabeled use): Note: Start at the beginning of conditioning therapy and continue until engraftment or until mucositis resolves (~30 days) Oral: 200 mg 3 times/day I.V.: 250 mg/m2/dose every 12 hours
Bone marrow transplant recipients (unlabeled use): I.V.: Allogeneic patients who are HSV and CMV seropositive: 500 mg/m2/dose (10 mg/kg) every 8 hours; for clinically-symptomatic CMV infection, consider replacing acyclovir with ganciclovir
DOSING: PEDIATRIC — Note: Obese patients should be dosed using ideal body weight
(For additional information see "Acyclovir: Pediatric drug information")
Genital HSV: I.V.: Children 12 years: Refer to adult dosing. Oral: Initial episode (unlabeled use): 40-80 mg/kg/day divided into 3-4 doses for 5-10 days (maximum: 1 g/day) Chronic suppression (unlabeled use; limited data): 80 mg/kg/day in 3 divided doses (maximum: 1 g/day), re-evaluate after 12 months of treatment
Herpes labialis (cold sores): Topical: Children 12 years: Refer to adult dosing.
Herpes zoster (shingles): I.V.: Children <12 years (immunocompromised): 20 mg/kg/dose every 8 hours for 7 days Children 12 years: Refer to adult dosing.
HSV encephalitis: I.V.: Children 3 months to 12 years: 20 mg/kg/dose every 8 hours for 10 days (per manufacturer's labeling); dosing for 14-21 days also reported Children 12 years: Refer to adult dosing.
Mucocutaneous HSV: I.V.: Children <12 years (immunocompromised): 10 mg/kg/dose every 8 hours for 7 days Children 12 years: Refer to adult dosing.
Neonatal HSV: I.V.: Neonate: Birth to 3 months: 10 mg/kg/dose every 8 hours for 10 days (manufacturer's labeling); 15 mg/kg/dose or 20 mg/kg/dose every 8 hours for 14-21 days has also been reported
Varicella-zoster (chickenpox): Begin treatment within the first 24 hours of rash onset: Oral: Children 2 years and 40 kg (immunocompetent): 20 mg/kg/dose (up to 800 mg/dose) 4 times/day for 5 days Children >40 kg: Refer to adult dosing. I.V.: Children <1 year (immunocompromised, unlabeled use): 10 mg/kg/dose every 8 hours for 7-10 days Children 1 year: Refer to adult dosing.
Prevention of HSV reactivation in HIV-positive patients, for use only when recurrences are frequent or severe (unlabeled use): Oral: 80 mg/kg/day in 3-4 divided doses
Prevention of HSV reactivation in HSCT (unlabeled use): Note: Start at the beginning of conditioning therapy and continue until engraftment or until mucositis resolves (~30 days): I.V.: 250 mg/m2/dose every 8 hours or 125 mg/m2/dose every 6 hours
Bone marrow transplant recipients (unlabeled use): I.V.: Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSING: RENAL IMPAIRMENT Oral: Clcr 10-25 mL/minute/1.73 m2: Normal dosing regimen 800 mg every 4 hours: Administer 800 mg every 8 hours Clcr <10 mL/minute/1.73 m2: Normal dosing regimen 200 mg every 4 hours, 200 mg every 8 hours, or 400 mg every 12 hours: Administer 200 mg every 12 hours Normal dosing regimen 800 mg every 4 hours: Administer 800 mg every 12 hours
I.V.: Clcr 25-50 mL/minute/1.73 m2: Administer recommended dose every 12 hours Clcr 10-25 mL/minute/1.73 m2: Administer recommended dose every 24 hours Clcr <10 mL/minute/1.73 m2: Administer 50% of recommended dose every 24 hours
Hemodialysis: Administer dose after dialysis
Peritoneal dialysis: No supplemental dose needed
CAVH: 3.5 mg/kg/day
CVVHD/CVVH: Adjust dose based upon Clcr 30 mL/minute
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule: 200 mg Zovirax®: 200 mg
Cream, topical: Zovirax®: 5% (2 g, 5 g)
Injection, powder for reconstitution, as sodium: 500 mg, 1000 mg Zovirax®: 500 mg [DSC]
Injection, solution, as sodium [preservative free]: 25 mg/mL (20 mL, 40 mL); 50 mg/mL (10 mL, 20 mL)
Ointment, topical: Zovirax®: 5% (15 g)
Suspension, oral: 200 mg/5 mL (480 mL) Zovirax®: 200 mg/5 mL (480 mL) [banana flavor]
Tablet: 400 mg, 800 mg Zovirax®: 400 mg, 800 mg
DOSAGE FORMS: CONCISE Capsule: 200 mg Zovirax®: 200 mg
Cream, topical: Zovirax®: 5% (2 g, 5 g)
Injection, powder for reconstitution: 500 mg, 1000 mg
Injection, solution [preservative free]: 25 mg/mL (20 mL, 40 mL); 50 mg/mL (10 mL, 20 mL)
Ointment, topical: Zovirax®: 5% (15 g)
Suspension, oral: 200 mg/5 mL Zovirax®: 200 mg/5 mL
Tablet: 400 mg, 800 mg Zovirax®: 400 mg, 800 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Excludes cream, ointment
ADMINISTRATION Oral: May be administered with or without food.
I.V.: Avoid rapid infusion; infuse over 1 hour to prevent renal damage; maintain adequate hydration of patient; check for phlebitis and rotate infusion sites
Topical: 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.
COMPATIBILITY — Stable in D5W, D5NS, D51/4NS, D51/2NS, LR, NS.
Incompatible with blood products and protein-containing solutions.
Y-site administration: Compatible: Allopurinol, amikacin, amphotericin B cholesteryl sulfate complex, ampicillin, cefamandole, cefazolin, cefoperazone, cefotaxime, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, chloramphenicol, cimetidine, clindamycin, co-trimoxazole, dexamethasone, dimenhydrinate, diphenhydramine, docetaxel, doxorubicin liposome, doxycycline, erythromycin lactobionate, etoposide, famotidine, filgrastim, fluconazole, gatifloxacin, gentamicin, granisetron, heparin, hydrocortisone sodium succinate, hydromorphone, imipenem/cilastatin, linezolid, lorazepam, magnesium sulfate, melphalan, methylprednisolone sodium succinate, metoclopramide, metronidazole, multivitamins, nafcillin, oxacillin, paclitaxel, penicillin G potassium, pentobarbital, perphenazine, piperacillin, potassium chloride, propofol, ranitidine, remifentanil, sodium bicarbonate, tacrolimus, teniposide, theophylline, thiotepa, ticarcillin, tobramycin, vancomycin, zidovudine. Incompatible: Amifostine, amsacrine, aztreonam, cefepime, dobutamine, dopamine, fludarabine, foscarnet, gemcitabine, idarubicin, levofloxacin, ondansetron, piperacillin/tazobactam, sargramostim, vinorelbine. Variable (consult detailed reference): Cisatracurium, diltiazem, meperidine, meropenem, morphine, TPN.
Compatibility when admixed: Compatible: Fluconazole. Incompatible: Dobutamine, dopamine. Variable (consult detailed reference): Meropenem.
USE — Treatment of genital herpes simplex virus (HSV), herpes labialis (cold sores), herpes zoster (shingles), HSV encephalitis, neonatal HSV, mucocutaneous HSV in immunocompromised patients, varicella-zoster (chickenpox)
USE - UNLABELED / INVESTIGATIONAL — Prevention of HSV reactivation in HIV-positive patients; prevention of HSV reactivation in hematopoietic stem-cell transplant (HSCT); prevention of HSV reactivation during periods of neutropenia in patients with acute leukemia
ADVERSE REACTIONS SIGNIFICANT Systemic: Oral:
>10%: Central nervous system: Malaise (12%)
1% to 10%: Central nervous system: Headache (2%) Gastrointestinal: Nausea (2% to 5%), vomiting (3%), diarrhea (2% to 3%)
Systemic: Parenteral:
1% to 10%: Dermatologic: Hives (2%), itching (2%), rash (2%) Gastrointestinal: Nausea/vomiting (7%) Hepatic: Liver function tests increased (1% to 2%) Local: Inflammation at injection site or phlebitis (9%) Renal: BUN increased (5% to 10%), creatinine increased (5% to 10%), acute renal failure
Topical:
>10%: Dermatologic: Mild pain, burning, or stinging (ointment 30%)
1% to 10%: Dermatologic: Pruritus (ointment 4%), itching
All forms: <1% (Limited to important or life-threatening): Abdominal pain, aggression, agitation, alopecia, anaphylaxis, anemia, angioedema, anorexia, ataxia, coma, confusion, consciousness decreased, delirium, desquamation, diarrhea, disseminated intravascular coagulopathy (DIC), dizziness, dry lips, dysarthria, encephalopathy, erythema multiforme, fatigue, fever, gastrointestinal distress, hallucinations, hematuria, hemolysis, hepatitis, hyperbilirubinemia, hypotension, insomnia, jaundice, leukocytoclastic vasculitis, leukocytosis, leukopenia, local tissue necrosis (following extravasation), lymphadenopathy, mental depression, myalgia, neutrophilia, paresthesia, peripheral edema, photosensitization, pruritus, psychosis, renal failure, seizure, somnolence, sore throat, Stevens-Johnson syndrome, thrombocytopenia, thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), thrombocytosis, toxic epidermal necrolysis, tremor, urticaria, visual disturbances
CONTRAINDICATIONS — Hypersensitivity to acyclovir, valacyclovir, or any component of the formulation
WARNINGS / PRECAUTIONS — Use with caution in immunocompromised patients; thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) has been reported. Use caution in the elderly, pre-existing renal disease, or in those receiving other nephrotoxic drugs. Maintain adequate hydration during oral or intravenous therapy. Use I.V. preparation with caution in patients with underlying neurologic abnormalities, serious hepatic or electrolyte abnormalities, or substantial hypoxia.
Safety and efficacy of oral formulations have not been established in pediatric patients <2 years of age.
Chickenpox: Treatment should begin within 24 hours of appearance of rash; oral route not recommended for routine use in otherwise healthy children with varicella, but may be effective in patients at increased risk of moderate to severe infection (>12 years of age, chronic cutaneous or pulmonary disorders, long-term salicylate therapy, corticosteroid therapy).
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.
Herpes labialis: For external use only to the lips and face; do not apply to eye or inside the mouth or nose. Treatment should begin with the first signs or symptoms.
Herpes zoster: Acyclovir should be started within 72 hours of appearance of rash to be effective.
ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Does not affect absorption of oral acyclovir.
PREGNANCY RISK FACTOR — B (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. Acyclovir has been shown to cross the human placenta. There are no adequate and well-controlled studies in pregnant women. Results from a pregnancy registry, established in 1984 and closed in 1999, did not find an increase in the number of birth defects with exposure to acyclovir when compared to those expected in the general population. However, due to the small size of the registry and lack of long-term data, the manufacturer recommends using during pregnancy with caution and only when clearly needed. Data from the pregnancy registry may be obtained from GlaxoSmithKline.
LACTATION — Enters breast milk/use with caution (AAP rates "compatible")
BREAST-FEEDING CONSIDERATIONS — Nursing mothers with herpetic lesions near or on the breast should avoid breast-feeding. Limited data suggest exposure to the nursing infant of ~0.3 mg/kg/day following oral administration of acyclovir to the mother.
DIETARY CONSIDERATIONS — May be taken with or without food. Acyclovir 500 mg injection contains sodium ~50 mg (~2 mEq).
PRICING — (data from drugstore.com)Capsules (Acyclovir) 200 mg (30): $12.99
Capsules (Zovirax) 200 mg (30): $66.50
Cream (Zovirax) 5% (2): $42.53 5% (5): $94.81
Ointment (Zovirax) 5% (15): $105.18
Suspension (Acyclovir) 200 mg/5 mL (473): $82.68
Suspension (Zovirax) 200 mg/5 mL (473): $183.41
Tablets (Acyclovir) 400 mg (60): $28.99 800 mg (30): $24.99
Tablets (Zovirax) 400 mg (60): $242.78 800 mg (30): $236.13
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, liver enzymes, CBC
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Overdoses of up to 20 g have been reported. Symptoms of overdose include agitation, seizures, somnolence, confusion, elevated serum creatinine, and renal failure. In the event of overdose, sufficient urine flow must be maintained to avoid drug precipitation within renal tubules. Hemodialysis has resulted in up to 60% reduction in serum acyclovir levels.
CANADIAN BRAND NAMES — Apo-Acyclovir®; Gen-Acyclovir; Nu-Acyclovir; ratio-Acyclovir; Zovirax®
INTERNATIONAL BRAND NAMES — Abbovir (PL); ACERPES (DE); Acic Creme (DE); Acicloftal (IT); Aciclor (VE); Aciclosina (PE); Aciclovir (PL); Aciclovir-BC IV (AU); Acihexal (AU); Acivir Cream (IL, IN); Acivir Eye (IN); Acix (PL); Aclova (KR); Aclovir (HR, TH, TW); Aclovirax (HK); ACS (KR); Activir (FR); Acyclo-V (AU, BH); Acyclostad (PL); Acyclovir (PL); Acyclovir Stada (PL); Acyklowir (PL); Acylene (MY); Acyrova (KR); Acyvir (EC, HK, IT); Aias (KR); Antivir (PL); Apicol (CO); Apo-Acyclovir (CA, PL); Avorax (HK, MY, SG); Avorax Cream (MY); Awirol (PL); Azovir (ID); Bearax (SG); Cicloferon (MX); Cicloviral (CO); Clinovir (ID, TH); Clovicin (TW); Clovir (BR); Cloviran (CL); Colsor (TH); Cusiviral (ES, HK, MY, PL, SG); Cyclivex (ZA); Cyclomed (IL); Cyclorax (HK); Cyclostad (PH); Cyclovir (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TZ, UG, ZM, ZW); Cyllanvir (PH); Danovir (SG); Deherp (TH, TW); Dravyr (SG); Duvimex (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Entir (SG, TH); Erlvirax (SG); Euroclovir (HK); Eurovir (PY); Exavir (BR); Expit (UY); Gen-Acyclovir (CA); Hascovir (PL); Herpefug (DE); Herpesin (PL); Herpex (BH, IN, PL); Herpoviric (DE); Herpoviric Rp Creme (DE); Heviran (PL); Inmerax (CL); Juviral (DE); Laciken (MX); Lermex (TH); Libravir (EC); Lisovyr (AR, CL); Lovir (AU, HK, MY, NZ, SG); Lovire (ZA); Marvir (TH); Matrovir (ID); Maynor (ES); Medovir (AE, BF, BG, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SA, SC, SD, SG, SL, SN, SY, TZ, UG, YE, ZM, ZW); Nevirz (ID); Norum (TH); Nu-Acyclovir (CA); Olvit (MX); Oppvir (TH, TW); Opthavir (MX); Poviral (EC); Proviral (AR); Qualiclovir (HK); Quavir (ID); Ranvir (TH); Ranviran (PL); ratio-Acyclovir (CA); Skirax (TW); Supra-Vir (IL); Supraviran (DE, PL); Supraviran Creme (AE, BH, CY, DE, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Syntovir (HK); Vacrax (MY); Vermis (TH); Vicorax (TH, TW); Viraban (NZ); Viracir (PL); Viralex-DS (PH); Virax (KR); Vircella (ID); Virest (MY, SG); Virex (CO); Virless (CN, TW); Viroclear (HK); Virogon (TH); Virolan (TW); Virolex (HR, PL); Viromed (TH); Virucid (HK); Virules (HK); Vivir (KR); Warviron (HK); Zetavir (MX); Zeven Cream (MY); Zevin (HK, TH); Zoral (HK, SG); Zoral Cream (MY); Zorax (SG); Zorel (ID); Zoter (ID); Zovir (DK); Zovirax [tabs./susp./ungt.] (PL); Zovirax (AE, AN, AR, AT, AU, BB, BD, BE, BF, BG, BH, BJ, BM, BO, BR, BS, BZ, CA, CH, CI, CL, CN, CR, CY, CZ, DE, DK, DO, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, HR, HU, ID, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KR, KW, LB, LR, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NO, NZ, OM, PA, PE, PH, PK, PR, PT, PY, QA, RU, SA, SC, SD, SE, SL, SN, SR, SV, SY, TR, TT, TW, TZ, UG, UY, YE, ZA, ZM, ZW); Zumasid (ID); Zyclir (AU); Zyclorax (ID); Zyvir (KE)
MECHANISM OF ACTION — 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.
PHARMACODYNAMICS / KINETICS Absorption: Oral: 15% to 30%
Distribution: Vd: 0.8 L/kg (63.6 L): Widely (eg, brain, kidney, lungs, liver, spleen, muscle, uterus, vagina, CSF)
Protein binding: 9% to 33%
Metabolism: Converted by viral enzymes to acyclovir monophosphate, and further converted to diphosphate then triphosphate (active form) by cellular enzymes
Bioavailability: Oral: 10% to 20% with normal renal function (bioavailability decreases with increased dose)
Half-life elimination: Terminal: Neonates: 4 hours; Children 1-12 years: 2-3 hours; Adults: 3 hours
Time to peak, serum: Oral: Within 1.5-2 hours
Excretion: Urine (62% to 90% as unchanged drug and metabolite)
PATIENT INFORMATION — This is not a cure for herpes (recurrences tend to continually reappear every 3-6 months after original infection), nor will this medication reduce the risk of transmission to others when lesions are present; avoid sexual intercourse when visible lesions are present. Take as directed for full course of therapy; do not discontinue even if feeling better. Oral doses may be taken with food.