Acyclovir (systemic)

Acyclovir (systemic): Drug information
Copyright 1978-2011 Lexicomp, Inc. All rights reserved.
(For additional information see “Acyclovir (systemic): Patient drug information” and see “Acyclovir (systemic): Pediatric drug information”)

Brand Names: U.S. Zovirax®
Brand Names: Canada Apo-Acyclovir®, Gen-Acyclovir, Mylan-Acyclovir, Novo-Acyclovir, Nu-Acyclovir, ratio-Acyclovir, Teva-Acyclovir, Zovirax®
Pharmacologic Category Antiviral Agent
Dosing: Adult Note: Obese patients should be dosed using ideal body weight
Genital herpes simplex virus (HSV) infection:

I.V.: Immunocompetent: Initial episode, severe: 5 mg/kg/dose every 8 hours for 5-7 days or 5-10 mg/kg/dose every 8 hours for 2-7 days, follow with oral therapy to complete at least 10 days of therapy (CDC, 2010)

Oral:

Initial episode: 200 mg every 4 hours while awake (5 times/day) for 10 days or 400 mg 3 times/day for 7-10 days (CDC, 2010)

Recurrence: 200 mg every 4 hours while awake (5 times/day) for 5 days (per manufacturer’s labeling; begin at earliest signs of disease)

Alternatively, the following regimens are also recommended by the CDC: 400 mg 3 times/day for 5 days; 800 mg twice daily for 5 days; 800 mg 3 times/day for 2 days (CDC, 2010)

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)

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: Treatment: 5 mg/kg/dose every 8 hours for 7 days (Leflore, 2000); dosing for up to 14 days also reported

Oral (unlabeled use): Immunocompromised: 400 mg 5 times/day for 7 days (Leflore, 2000)

Orolabial HSV (unlabeled use): Oral (immunocompetent):

Treatment: 200-400 mg 5 times/day for 5 days (Cernik, 2008; Leflore, 2000; Spruance, 1990) for episodic/recurrent treatment; for initial treatment, limited data are available, 200 mg 5 times/day or 400 mg 3 times/day for 7-10 days has been recommended by some clinicians.

Chronic suppression: 400 mg 2 times/day (has been clinically evaluated for up to 1 year) (Cernik, 2008; Rooney, 1993)

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.:

Manufacturer’s labeling (immunocompromised): 10 mg/kg/dose every 8 hours for 7 days

CDC HIV guidelines (immunocompromised): 10-15 mg/kg/dose every 8 hours for 7-10 days

Prevention of HSV reactivation in HIV-positive patients (unlabeled use): Oral: 400-800 mg 2-3 times/day (CDC, 2010)

Prevention of HSV reactivation in HSCT (unlabeled use): CDC recommendation: 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

Prevention of VZV reactivation in allogeneic HSCT (unlabeled use): NCCN guidelines: Oral: 800 mg twice a day

Prevention of CMV reactivation in low-risk allogeneic HSCT (unlabeled use): NCCN guidelines: Note: Requires close monitoring (due to weak activity); not for use in patients at high risk for CMV disease: Oral: 800 mg 4 times/day

Treatment of disseminated HSV or VZV or empiric treatment of suspected encephalitis in immunocompromised patients with cancer: (unlabeled use): NCCN guidelines: I.V.: 10-12 mg/kg/dose every 8 hours

Treatment of episodic HSV infection in HIV-positive patient (unlabeled use): Oral: 400 mg 3 times/day for 5-10 days (CDC, 2010)

Dosing: Pediatric
(For additional information see “Acyclovir (systemic): Pediatric drug information”)

Note: Obese patients should be dosed using ideal body weight
Genital herpes simplex virus (HSV) infection:

I.V.: Children ≥12 years: Refer to adult dosing.

Oral:

Immunocompetent:

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

Immunocompromised (unlabeled use; CDC, 2009): Initial episode:

Children <45 kg: 60 mg/kg/day divided into 3 doses for 5-14 days (maximum: 1.2 g/day)

Adolescents: 400 mg twice daily for 5-14 days

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): Treatment: 10 mg/kg/dose every 8 hours for 7 days

Children ≥12 years (immunocompromised): Treatment: 5-10 mg/kg/dose every 8 hours for 7 days (Leflore, 2000); dosing for up to 14 days also reported

Neonatal HSV: I.V.: Infants: Birth to 3 months: 10 mg/kg/dose every 8 hours for 10 days (manufacturer’s labeling); 20 mg/kg/dose every 8 hours for 14 (skin and mucous membrane disease) to 21 days (CNS disease) (CDC, 2010)

Orolabial HSV (unlabeled use): Oral: Children 1-6 years (immunocompetent, gingivostomatitis): Treatment of primary infection: 15 mg/kg/dose (maximum: 200 mg/dose) 5 times/day for 7 days, initiated within 72 hours of symptom onset (Amir, 1997)

Varicella-zoster (chickenpox): Begin treatment within the first 24 hours of rash onset:

Oral: Note: The CDC HIV guidelines recommended duration of therapy is 7-10 days or until no new lesions for 48 hours (for patients with mild varicella and no or moderate immune suppression).

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.:

Manufacturer’s labeling (immunocompromised):

Children <12 years: 20 mg/kg/dose every 8 hours for 7 days

Children ≥12 years: 10 mg/kg/dose every 8 hours for 7 days

CDC HIV guidelines (immunocompromised):

Children <1 year: 10 mg/kg/dose every 8 hours for 7-10 days or until no new lesions for 48 hours

Children ≥1 year: 10 mg/kg/dose or 500 mg/m2/dose every 8 hours for 7-10 days or until no new lesions for 48 hours

Adolescents: Refer to adult dosing.

Varicella-zoster acute retinal necrosis infection in HIV-exposed/-positive patients (unlabeled use; CDC, 2009): I.V.: Infants and Children: 10-15 mg/kg/dose every 8 hours for 10-14 days, followed by valacyclovir for 4-6 weeks

Prevention of HSV reactivation in HIV-exposed/-positive patients (unlabeled use; CDC, 2009): Oral: 20 mg/kg/dose twice daily (maximum: 400 mg/dose)

Prevention of HSV reactivation in HSCT (unlabeled use): CDC recommendation: 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

Dosing: Geriatric 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 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

Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days): Dialyzable (60% reduction following a 6-hour session): I.V.: 2.5-5 mg/kg every 24 hours (Heintz, 2009). Note: Dosing dependent on the assumption of 3 times/week, complete IHD sessions.

Peritoneal dialysis (PD): Administer 50% of normal dose once daily; no supplemental dose needed

Continuous renal replacement therapy (CRRT) (Heintz, 2009; Trotman, 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1-2 L/hour and minimal residual renal function) and should not supersede clinical judgment:

CVVH: I.V.: 5-10 mg/kg every 24 hours

CVVHD/CVVHDF: I.V.: 5-10 mg/kg every 12-24 hours

Note: The higher end of dosage range (eg, 10 mg/kg every 12 hours for CVVHDF) is recommended for viral meningoencephalitis and varicella-zoster virus infections.

Dosage Forms: U.S. Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral: 200 mg

Zovirax®: 200 mg

Injection, powder for reconstitution, as sodium [strength expressed as base]: 500 mg, 1000 mg

Injection, solution, as sodium [strength expressed as base, preservative free]: 50 mg/mL (10 mL, 20 mL)

Suspension, oral: 200 mg/5 mL (473 mL)

Zovirax®: 200 mg/5 mL (473 mL) [banana flavor]

Tablet, oral: 400 mg, 800 mg

Zovirax®: 400 mg

Zovirax®: 800 mg [scored]

Generic Equivalent Available: U.S. Yes
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. Avoid I.M. or SubQ administration.

Compatibility Stable in D5W, NS.
Incompatible with blood products and protein-containing solutions.

Y-site administration: Compatible: Allopurinol, amikacin, amphotericin B cholesteryl sulfate complex, ampicillin, anidulafungin, cefamandole, cefazolin, cefonicid, cefoperazone, ceforanide, cefotaxime, cefoxitin, ceftazidime, ceftizoxime, cefuroxime, cephapirin, chloramphenicol, cimetidine, clindamycin, co-trimoxazole, dexamethasone sodium phosphate, dimenhydrinate, docetaxel, doripenem, doxorubicin liposome, doxycycline, droperidol, erythromycin lactobionate, etoposide phosphate, famotidine, fentanyl, filgrastim, fluconazole, gallium nitrate, gatifloxacin, heparin, hydrocortisone sodium succinate, hydromorphone, imipenem/cilastatin, linezolid, lorazepam, magnesium sulfate, melphalan, methylprednisolone sodium succinate, metronidazole, milrinone, multivitamins, nafcillin, nalbuphine, oxacillin, paclitaxel, pemetrexed, penicillin G potassium, pentobarbital, perphenazine, piperacillin, potassium chloride, propofol, ranitidine, remifentanil, sodium bicarbonate, teniposide, tetracycline, theophylline, thiotepa, ticarcillin, tobramycin, vancomycin, zidovudine. Incompatible: Amifostine, amsacrine, aztreonam, cefepime, dobutamine, dopamine, fludarabine, foscarnet, gemcitabine, idarubicin, levofloxacin, ondansetron, piperacillin/tazobactam, sargramostim, tacrolimus, vinorelbine. Variable (consult detailed reference): Amifostine, amino acid solution, amsacrine, aztreonam, caffeine citrate, cefepime, cyclosporine, dobutamine, dopamine, fludarabine, foscarnet, gemcitabine, idarubicin, levofloxacin, ondansetron, pantoprazole, piperacillin/tazobactam, sargramostim, tacrolimus, total parenteral nutrition, TrophAmine®, vinorelbine.

Compatibility in syringe: Incompatible: Caffeine citrate, ceftriaxone, pantoprazole.

Use Treatment of genital herpes simplex virus (HSV) and HSV encephalitis
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 cancer; prevention of varicella zoster virus (VZV) reactivation in allogenic HSCT; prevention of CMV reactivation in low-risk allogeneic HSCT; treatment of disseminated HSV or VZV in immunocompromised patients with cancer; empiric treatment of suspected encephalitis in immunocompromised patients with cancer; treatment of initial and prophylaxis of recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) infections in immunocompromised patients
Medication Safety Issues
Sound-alike/look-alike issues:
Acyclovir may be confused with ganciclovir, Retrovir®, valacyclovir

Zovirax® may be confused with Doribax®, Valtrex®, Zithromax®, Zostrix®, Zyloprim®, Zyvox®

Adverse Reactions Significant
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%)

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

All forms: <1% (Limited to important or life-threatening): Abdominal pain, aggression, agitation, anemia, anorexia, ataxia, coma, confusion, consciousness decreased, delirium, desquamation, disseminated intravascular coagulopathy (DIC), dizziness, dysarthria, encephalopathy, fatigue, fever, gastrointestinal distress, hallucinations, hematuria, hemolysis, hepatitis, hyperbilirubinemia, hypotension, insomnia, jaundice, leukocytoclastic vasculitis, leukocytosis, leukopenia, lymphadenopathy, mental depression, myalgia, neutrophilia, pain, psychosis, renal failure, renal pain, seizure, somnolence, sore throat, thrombocytopenia, thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), thrombocytosis, visual disturbances

Contraindications Hypersensitivity to acyclovir, valacyclovir, or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:

• Renal effects: Renal failure (sometimes fatal) has been reported. Dehydration, pre-existing renal disease and nephrotoxic drugs increase risk; infuse over at least 1 hour to reduce risk of renal tubular damage.

• Thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS): Has been reported in immunocompromised patients receiving acyclovir.

Disease-related concerns:

• Renal impairment: Use with caution in patients with pre-existing renal impairment; dosage adjustments recommended.

• Varicella-zoster: Appropriate use: 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).

Concurrent drug therapy issues:

• Nephrotoxic drugs: Use with caution in patients receiving other nephrotoxic drugs.

Dosage form specific issues:

• Injection: Use I.V. preparation with caution in patients with underlying neurologic abnormalities, serious hepatic or electrolyte abnormalities, or substantial hypoxia.

Other warnings/precautions:

• Adequate hydration: Maintain adequate hydration during oral or intravenous therapy.

Drug Interactions
(For additional information: Launch Lexi-Interact™ Drug Interactions Program )
Mycophenolate: Acyclovir-Valacyclovir may increase the serum concentration of Mycophenolate. Mycophenolate may increase the serum concentration of Acyclovir-Valacyclovir. Risk C: Monitor therapy

Tenofovir: Acyclovir-Valacyclovir may decrease the excretion of Tenofovir. Risk C: Monitor therapy

Zidovudine: Acyclovir-Valacyclovir may enhance the CNS depressant effect of Zidovudine. Risk C: Monitor therapy

Zoster Vaccine: Acyclovir-Valacyclovir may diminish the therapeutic effect of Zoster Vaccine. Management: When possible, discontinue antiviral agents with anti-zoster activity (i.e., acyclovir, valacyclovir, famciclovir) for at least 24 hours prior to and 14 days after receiving a live attenuated zoster vaccine. Risk X: Avoid combination

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”; AAP 2001 update pending)
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. Some products may contain sodium.
Pricing: U.S. (www.drugstore.com)
Capsules (Zovirax)

200 mg (30): $96.99

Suspension (Acyclovir)

200 mg/5 mL (473): $126.00

Tablets (Acyclovir)

800 mg (30): $24.99

Tablets (Zovirax)

400 mg (60): $361.98

800 mg (30): $336.31

Monitoring Parameters Urinalysis, BUN, serum creatinine, liver enzymes, CBC
International Brand Names Acic (EE); Aciclodan (DK); Aciclor (VE); Aciclosina (PT); Acicvir (NZ); Aciherpin (PH); Acihexal (AU); Acivir Eye (IN); Acivirex (GT, HN, NI, SV); Aclovir (FI, TH, TW); ACS (KP); Activir (FR); Acyclo-V (AU, BH); Acyclovenir (IL); Acylene (MY); Acyrax (FI); Acyvir (EC, IT); Aisike (CL); Antix (NO); Asile (CL); Avir (VE); Avorax (HK); Cicloferon (CR, DO, GT, NI, PA, SV); Cicloviral (CO); Clinovir (ID, TH); Clovir (KP, PH); Colsor (TH); Covelay (PH); Cusiviral (MY, SG); Cyclivex (ZA); Cycloherp (HK); Cyclostad (PH); Cyclovir (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW); Cyllanvir (PH); Deherp (TH, TW); Docaciclo (BE); Dravyr (MY, SG); Duvimex (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Ecuvir (EC); Entir (SG, TH); Erlvirax (SG); Euroclovir (HK); Eurovir (PY); Expit (UY); Geavir (DK, SE); Helvevir (CH); Herax (ID); Herpesin (CZ); Herpetad (CR, DO, GT, HN, NI, PA, SV); Herpevex (MY); Herpevir (FR); Herpex (BH, IN); Herpizyg (TH); Heviran (PL); Lermex (TH); Licovir (ID); Lisovyr (AR, CN); Lovir (AU, NZ, PH); Lovire (ZA); Marvir (TH); 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, TN, TW, TZ, UG, YE, ZM, ZW); Molavir (ID); Norum (TH); Ozvir (AU); Poviral (AR); Qualiclovir (HK); Quavir (ID); Ranvir (TH); Reclovax (TH); Remex (FR); Skirax (TW); Vacrax (MY); Vermis (TH); Viralex-DS (PH); Viralis (ID); Viratop (BE); Virax (KP); Virest (SG); Virex (CO); Virless (MY, SG, TW); Viroclear (HK); Virogon (TH); Viromed (TH); Virzin (DE); Vivir (KP); Zevin (TH); Zodiac (KP); Zoral (HK, MY, SG); Zorax (SG); Zorexin (MY); Zoter (ID); Zoteran (PH); Zovir (DK); Zovirax (AE, AR, AT, AU, BB, BD, BE, BF, BG, BH, BJ, BM, BO, BR, BS, CH, CI, CN, CR, CY, CZ, DO, EC, EE, EG, ET, FI, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, ID, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KP, KW, LB, LR, LY, MA, ML, MR, MT, MU, MW, MY, NE, NG, NI, NL, NO, NZ, OM, PA, PE, PH, PK, PL, PR, PT, PY, QA, RU, SA, SC, SD, SE, SK, SL, SN, SV, SY, TN, TR, TT, TW, TZ, UG, UY, YE, ZA, ZM, ZW); 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)

 

 

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