(ay SYE kloe veer)
Oral:
Herpes zoster (shingles): Acute treatment of herpes zoster (shingles).
Herpes simplex virus (HSV), genital: Treatment of initial episodes and the management of recurrent episodes of genital herpes.
Varicella (chickenpox): Treatment of varicella (chickenpox).
Injection:
Herpes simplex virus (HSV), mucocutaneous infection in immunocompromised patients: Treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) in immunocompromised patients.
Herpes simplex virus (HSV), genital infection (severe): Treatment of severe initial clinical episodes of genital herpes in immunocompetent patients.
Herpes simplex encephalitis: Treatment of herpes simplex encephalitis.
Herpes simplex virus (HSV), neonatal: Treatment of neonatal herpes infections.
Herpes zoster (shingles) in immunocompromised patients: Treatment of herpes zoster (shingles) in immunocompromised patients.
Hypersensitivity to acyclovir, valacyclovir, or any component of the formulation
Herpes simplex virus (HSV), genital infection:
Immunocompetent:
IV: Initial episode, severe:
Manufacturer 's labeling: 5 mg/kg/dose every 8 hours for 5 to 7 days
Alternate recommendation: 5 to 10 mg/kg/dose every 8 hours for 2 to 7 days, follow with oral therapy to complete at least 10 days of therapy (CDC [Workowski 2015])
Oral:
Initial episode:
Manufacturer 's labeling: 200 mg 5 times daily while awake for 10 days
Alternate recommendation: 200 mg 5 times daily for 7 to 10 days or 400 mg 3 times daily for 7 to 10 days (CDC [Workowski 2015])
Recurrence: Note: Begin at earliest signs of disease
Manufacturer 's labeling: 200 mg 5 times daily while awake for 5 days
Alternate recommendation: 400 mg 3 times daily for 5 days or 800 mg twice daily for 5 days or 800 mg 3 times daily for 2 days (CDC [Workowski 2015])
Chronic suppression: 400 mg twice daily for up to 12 months (followed by re-evaluation); Note: Safety and efficacy have been documented in patients receiving daily therapy with acyclovir for up to 6 years (CDC [Workowski 2015])
HIV-infected patients (off-label use):
Initial or recurrent episodes: 400 mg 3 times daily for 5 to 14 days (HHS [OI adult 2015]) or 400 mg 3 times daily for 5 to 10 days (CDC [Workowski 2015])
Chronic suppressive therapy: 400 mg twice daily; continue indefinitely regardless of CD4 count in patients with severe recurrences of genital herpes or in patients who want to minimize frequency of recurrences (HHS [OI adult 2015]) or 400 to 800 mg 2 to 3 times daily (CDC [Workowski 2015])
HSV encephalitis: IV: Independent of HIV status:
Manufacturers labeling: 10 mg/kg/dose every 8 hours for 10 days
Alternate recommendation: 10 mg/kg/dose every 8 hours for 14 to 21 days (Red Book [AAP 2012])
HSV, mucocutaneous treatment:
Immunocompromised:
IV:
Manufacturer 's labeling: 5 mg/kg/dose every 8 hours for 7 days
Alternate recommendations: 5 to 10 mg/kg/dose every 8 hours for 7 days (Leflore 2000)
Oral (off-label use): 400 mg 5 times daily for 7 days (Leflore 2000)
HIV-infected patients: (off-label use)
IV: 5 mg/kg/dose every 8 hours; may switch to oral after lesions begin to heal (HHS [OI adult 2015])
Oral: After initial IV therapy, may switch to 400 mg 3 times daily; continue until lesions are completely healed (HHS [OI adult 2015])
HSV, orolabial (cold sores) (off-label use): Oral:
Immunocompetent:
Treatment: (episodic/recurrent): 200 to 400 mg 5 times daily for 5 days (Cernik 2008; Leflore 2000; Spruance 1990).
Chronic suppression: 400 mg 2 times daily (has been clinically evaluated for up to 1 year) (Cernik 2008; Rooney 1993)
HIV-infected patients: Treatment: 400 mg 3 times daily for 5 to 10 days (HHS [OI adult 2015])
Herpes zoster (shingles), treatment:
Manufacturer 's labeling:
IV: Immunocompromised: 10 mg/kg/dose every 8 hours for 7 days
Oral: Immunocompetent: 800 mg 5 times daily for 7 to 10 day
Alternate recommendations: HIV-infected patients (HHS [OI adult 2015]):
IV: Extensive cutaneous lesions or visceral involvement: 10 to 15 mg/kg/dose every 8 hours until clinical improvement; switch to oral famciclovir or valacyclovir (preferred) or acyclovir (alternative) to complete a 10 to 14 day course when formation of new lesions has ceased and signs/symptoms of visceral infection are improving
Oral (off-label use): Acute localized infection (as an alternative to valacylovir or famciclovir): 800 mg 5 times daily for 7 to 10 days; consider longer duration if lesions resolve slowly
Prevention of early HSV reactivation in seropositive hematopoietic stem cell transplant (HSCT) recipients (off-label use):Note: Start at the beginning of conditioning therapy and continue until engraftment or until mucositis resolves (~30 days) (Tomblyn 2009)
Oral: 400 to 800 mg twice daily
IV: 250 mg/m2 every 12 hours
Prevention of late HSV reactivation in seropositive HSCT recipients (off-label use): Oral: 800 mg twice daily; continue therapy for 1 year after HSCT (Tomblyn 2009).
Prevention of HSV reactivation in seropositive patients undergoing acute myeloid leukemia induction or reinduction (off-label use): Oral: 400 mg twice daily; continue during active therapy and throughout periods of neutropenia (Bergmann 1995; Freifeld 2011)
Prevention of VZV reactivation in HSCT recipients (off-label use): Oral: 800 mg twice daily; continue therapy for 1 year after HSCT (Tomblyn 2009).
Prophylaxis of CMV in low-risk allogeneic HSCT (off-label use; alternate therapy): Note: Begin at engraftment and continue to day 100; requires close monitoring for CMV reactivation (due to weak activity); not for use in patients at high risk for CMV disease (Tomblyn 2009)
Oral: 800 mg 4 times daily
IV: 500 mg/m2 every 8 hours
Varicella (chickenpox), treatment: Begin treatment within the first 24 hours of rash onset:
Oral:
Immunocompetent (>40 kg): 800 mg 4 times daily for 5 days
HIV-infected patients (off-label use): Uncomplicated cases (as an alternative to valacyclovir or famciclovir): 800 mg 5 times daily for 5 to 7 days (HHS [OI adult 2015])
IV: HIV- infected patients (off-label use): Severe or complicated cases: 10 to 15 mg/kg/dose every 8 hours for 7 to 10 days; may switch to oral famciclovir or valacyclovir (preferred) or acyclovir (alternative) after defervescence if no evidence of visceral involvement (HHS [OI adult 2015])
Varicella-zoster virus acute retinal necrosis (ARN) in HIV-infected patients (off-label use): IV: 10 to 15 mg/kg/dose every 8 hours for 10 to 14 days, followed by valacyclovir for 6 weeks plus intravitreal ganciclovir twice weekly for 1 to 2 doses (HHS [OI adult 2015])
Refer to adult dosing.
Herpes simplex virus (HSV), genital infection:
IV: Children ≥12 years and Adolescents: Immunocompetent: Initial episode, severe: Manufacturer 's labeling: 5 mg/kg/dose every 8 hours for 5 to 7 days
Oral:
Infants and Children <12 years: Immunocompetent (off-label use):
Initial episode: 40 to 80 mg/kg/day divided into 3 to 4 doses for 5-10 days (maximum: 1,000 mg daily) (Red Book [AAP 2012])
Chronic suppression: 40 to 80 mg/kg/day in 3 divided doses for ≤12 months; (maximum: 1,000 mg daily) (Red Book [AAP 2009])
Children ≥12 years and Adolescents: Immunocompetent (off-label use):
Initial episode: 200 mg every 4 hours while awake (5 times daily) or 400 mg 3 times daily for 7 to 10 days; treatment can be extended beyond 10 days if healing is not complete (Red Book [AAP 2012])
Chronic suppression: 800 mg daily in 2 divided doses for ≤12 continuous months (Red Book [AAP 2012])
Children: HIV-exposed/-positive (off-label use):
Children <45 kg:
Initial episode: 60 mg/kg/day divided into 3 doses daily for 5 to 14 days (maximum: 1,200 mg daily) (CDC 2009)
Chronic suppression: 20 mg/kg/dose twice daily (maximum dose: 400 mg) (CDC 2009)
Children ≥45 kg:
Initial episode: 400 mg twice daily for 5 to 14 days (CDC 2009)
Chronic suppression: 20 mg/kg/dose twice daily (maximum dose: 400 mg) (CDC 2009)
Children <12 years: Recurrence: Immunocompetent: Oral: 20 to 25 mg/kg/dose twice daily; maximum dose: 400 mg (Bradley 2011)
Children ≥12 years: Recurrence: Immunocompetent:
Manufacturer 's labeling: 200 mg every 4 hours while awake (5 times daily) for 5 days
Alternate recommendation: 400 mg 3 times daily for 5 days or 800 mg twice daily for 5 days or 800 mg 3 times daily for 2 days (CDC [Workowski 2015]; Red Book [AAP 2015])
Adolescents: HIV-positive patients: (off-label use): Refer to adult dosing.
HSV encephalitis: IV:
Infants and Children 3 months to <12 years:
Immunocompetent:
Manufacturers labeling: 20 mg/kg/dose every 8 hours for 10 days. Note: Doses ≥20 mg/kg may be associated with a higher incidence of nephrotoxicity (Red Book [AAP 2012])
Alternate recommendation: 10 to 15 mg/kg/dose every 8 hours for 14 to 21 days (Red Book [AAP 2012])
HIV-exposed/-positive: 10 mg/kg/dose every 8 hours for 21 days; do not discontinue therapy until a repeat HSV DNA PCR assay of the cerebrospinal fluid is negative (CDC 2009)
Children ≥12 years and Adolescents: Independent of HIV status:
Manufacturer's labeling: 10 mg/kg/dose every 8 hours for 10 days
Alternate recommendation: 10 mg/kg/dose every 8 hours for 14 to 21 days (Red Book [AAP 2012])
HSV gingivostomatitis (off-label use): HIV-exposed/-positive:
Mild, symptomatic: Oral: Infants and Children: 20 mg/kg/dose 3 times daily for 5 to 10 days (maximum dose: 400 mg) (CDC 2009)
Moderate to severe, symptomatic: IV: Infants and Children: 5 to 10 mg/kg/dose every 8 hours; Note: switch to oral therapy once lesions begin to regress (CDC 2009)
HSV, mucocutaneous treatment:
Immunocompromised:
IV:
Infants, Children, and Adolescents: 10 mg/kg/dose every 8 hours for 7 to 14 days (Red Book [AAP 2012])
Oral (off-label use):
Children ≥ 2 years and Adolescents: 1,000 mg daily in 3 to 5 divided doses for 7 to 14 days; some suggest the maximum daily dose should not exceed 80 mg/kg/day (Red Book [AAP 2009]; Red Book [AAP 2012])
HIV-infected patients (off-label use): Adolescents: IV, Oral: Refer to adult dosing.
Suppression, chronic (cutaneous, ocular) episodes: Immunocompromised: Oral:
Infants and Children (HIV-exposed/-positive): 20 mg/kg/dose twice daily for 5 to 14 days; maximum dose: 400 mg (CDC 2009)
Children and Adolescents ≥12 years (independent of HIV status): 400 mg twice daily for up to 12 months (Red Book [AAP 2012])
HSV, neonatal: IV: Infants: Birth to 3 months: Treatment:
Manufacturer's labeling: 10 mg/kg/dose every 8 hours for 10 days
Alternate recommendations: 20 mg/kg/dose every 8 hours for 14 days (skin and mucous membrane disease) to 21 days (disseminated disease and CNS disease) (CDC [Workowski 2015]; Kimberlin 2013; Red Book [AAP 2012])
HSV, orolabial (cold sores) (off-label use): Oral:
Immunocompetent: Chronic suppression: Children: 30 mg/kg/day in 3 divided doses for up to 12 months (maximum: 1,000 mg/day). Note: Re-evaluate after 12 months (Red Book [AAP 2012])
HIV-infected patients: Treatment: Adolescents: Refer to adult dosing.
Herpes zoster (shingles), treatment:
IV:
Immunocompetent (off-label use):
Infants: 10 mg/kg/dose every 8 hours for 7 to 10 days (Red Book [AAP 2012])
Children ≥1 year and Adolescents: 500 mg/m2/dose every 8 hours for 7 to 10 days; some experts recommend 10 mg/kg/dose every 8 hours (Red Book [AAP 2012])
Immunocompromised:
Children <12 years: (off-label dose): 10 mg/kg/dose every 8 hours for 7 to 10 days (Red Book [AAP 2012])
Children ≥12 years and Adolescents: Manufacturer 's labeling: Refer to adult dosing.
HIV-infected patients: Adolescents (off-label dose): Extensive cutaneous lesions or visceral involvement: Refer to adult dosing.
Oral:
Immunocompetent:
Children ≥12 years and Adolescents (off-label dose): 800 mg 5 times daily for 5 to 7 days (Red Book [AAP 2012])
Immunocompromised: HIV-infected patients (off-label use): Acute localized infection (as an alternative to valacyclovir or famciclovir): Adolescents: Refer to adult dosing.
Prevention of HSV reactivation in HIV-exposed/-positive patients (off-label use): Oral: Children: 20 mg/kg/dose twice daily (maximum: 400 mg per dose) (CDC 2009)
Prevention of early HSV reactivation in seropositive hematopoietic stem cell transplant (HSCT) recipients (off-label use):Note: Start at the beginning of conditioning therapy and continue until engraftment or until mucositis resolves (~30 days) (Tomblyn 2009):
Oral:
Infants, Children, and Adolescents <40 kg (alternate therapy): 60 to 90 mg/kg/day in 2 to 3 divided doses
Children and Adolescents ≥40 kg: 400 to 800 mg twice daily
IV:
Infants, Children, and Adolescents <40 kg: 250 mg/m2 every 8 hours or 125 mg/m2 every 6 hours (maximum daily dose: 80 mg/kg/day)
Children and Adolescents ≥40 kg: 250 mg/m2 every 12 hours
Prevention of late HSV reactivation in seropositive HSCT recipients (off-label use): Note: Continue therapy for 1 year after HSCT (Tomblyn 2009).
Infants, Children, and Adolescents <40 kg: Oral: 60 to 90 mg/kg/day in 2 to 3 divided doses (maximum dose: 800 mg twice daily)
Children and Adolescents ≥40 kg: Oral: 800 mg twice daily
Prevention of VZV reactivation in HSCT recipients (off-label use): Note: Continue therapy for 1 year after HSCT (Tomblyn 2009)
Infants, Children, and Adolescents <40 kg: Oral: 60 to 80 mg/kg/day in 2 to 3 divided doses
Children and Adolescents ≥40 kg: Oral: 800 mg twice daily
Prophylaxis of CMV in low-risk allogeneic HSCT (off-label use; alternate therapy): Note: Begin at engraftment and continue to day 100; requires close monitoring for CMV reactivation (due to weak activity); not for use in patients at high risk for CMV disease (Tomblyn 2009)
Oral:
Infants, Children, and Adolescents <40 kg: 600 mg/m2 4 times daily
Children and Adolescents ≥40 kg: 800 mg 4 times daily
IV: Infants, Children, and Adolescents: 500 mg/m2 every 8 hours
Varicella (chickenpox), treatment: Begin treatment within the first 24 hours of rash onset:
Oral:
Immunocompetent:
Children ≥2 years and ≤40 kg: 20 mg/kg/dose (maximum: 800 mg per dose) 4 times daily for 5 days
Children >40 kg: Refer to adult dosing.
HIV-infected patients (off-label use):
Infants and Children: Mild, uncomplicated disease and no or moderate immune suppression: 20 mg/kg/dose (maximum dose: 800 mg) 4 times daily for 7 to 10 days or until no new lesions for 48 hours (CDC 2009)
Adolescents: Uncomplicated cases (as an alternative to valacyclovir or famciclovir): Refer to adult dosing.
IV:
Immunocompetent (off-label use): Children ≥2 years: 10 mg/kg/dose or 500 mg/m2/dose every 8 hours for 7 to 10 days (CDC 2009; Red Book [AAP 2012])
Immunocompromised (off-label use):
Infants (off-label dose): 10 mg/kg/dose every 8 hours for 7 to 10 days (Red Book [AAP 2012])
Children and Adolescents (off-label dose): 500 mg/m2/dose every 8 hours for 7 to 10 days; some experts recommend 10 mg/kg/dose every 8 hours (Red Book [AAP 2012])
HIV-exposed/-positive (off-label use):
Infants: 10 mg/kg/dose every 8 hours for 7 to 10 days or until no new lesions for 48 hours (CDC 2009)
Children ≥1 year: 10 mg/kg/dose or 500 mg/m2/dose every 8 hours for 7 to 10 days or until no new lesions for 48 hours (CDC 2009)
Adolescents: Refer to adult dosing.
Varicella-zoster virus acute retinal necrosis in HIV-exposed/-positive patients (off-label use): IV:
Infants and Children: 10 to 15 mg/kg/dose every 8 hours for 10 to 14 days, followed by oral acyclovir or valacyclovir for 4 to 6 weeks (CDC 2009)
Adolescents: Refer to adult dosing.
Oral:
CrCl 10-25 mL/minute/1.73 m2: Normal dosing regimen 800 mg 5 times daily: Administer 800 mg every 8 hours
CrCl <10 mL/minute/1.73 m2:
Normal dosing regimen 200 mg 5 times daily or 400 mg every 12 hours: Administer 200 mg every 12 hours
Normal dosing regimen 800 mg 5 times daily: Administer 800 mg every 12 hours
Intermittent hemodialysis (IHD): Dialyzable (60% reduction following a 6-hour session):
Normal dosing regimen 200 mg 5 times daily or 400 mg every 12 hours: Administer 200 mg every 12 hours; administer after hemodialysis on dialysis days
Normal dosing regimen 800 mg 5 times daily: Administer 800 mg every 12 hours; administer after hemodialysis on dialysis days
IV:
CrCl 25-50 mL/minute/1.73 m2: Administer recommended dose every 12 hours
CrCl 10-25 mL/minute/1.73 m2: Administer recommended dose every 24 hours
CrCl <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): 2.5-5 mg/kg every 24 hours (Heintz 2009). Note: Dosing dependent on the assumption of 3 times weekly, complete IHD sessions.
Peritoneal dialysis (PD): Administer 50% of normal dose once daily; no supplemental dose needed (Aronoff 2007)
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: 5-10 mg/kg every 24 hours
CVVHD/CVVHDF: 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.
Oral, IV: There are no dosage adjustments provided in the manufacturers labeling; use caution in patients with severe impairment.
Powder for injection: Reconstitute acyclovir 500 mg powder with SWFI 10 mL; do not use bacteriostatic water containing benzyl alcohol or parabens. For intravenous infusion, dilute in D5W or NS to a final concentration ≤7 mg/mL. Concentrations >10 mg/mL increase the risk of phlebitis.
Oral: May be administered with or without food.
IV: Avoid rapid infusion; infuse over 1 hour to prevent renal damage; maintain adequate hydration of patient; check for phlebitis and rotate infusion sites. Avoid IM or SubQ administration.
May be taken with or without food. Some products may contain sodium.
Capsule, oral suspension, tablet: Store at controlled room temperature of 15 ‚ °C to 25 ‚ °C (59 ‚ °F to 77 ‚ °F); protect from capsule and tablet from moisture.
Injection: Store powder at controlled room temperature of 15 ‚ °C to 25 ‚ °C (59 ‚ °F to 77 ‚ °F). Reconstituted solutions remain stable for 12 hours at room temperature. Do not refrigerate reconstituted solutions or solutions diluted for infusion as they may precipitate. Once diluted for infusion with NS or D5W, use within 24 hours.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Zovirax: 200 mg [contains fd&c blue #2 (indigotine), parabens]
Generic: 200 mg
Solution, Intravenous, as sodium [strength expressed as base]:
Generic: 50 mg/mL (10 mL, 20 mL)
Solution Reconstituted, Intravenous, as sodium [strength expressed as base]:
Generic: 500 mg (1 ea); 1000 mg (1 ea)
Suspension, Oral:
Zovirax: 200 mg/5 mL (473 mL) [contains methylparaben, propylparaben; banana flavor]
Generic: 200 mg/5 mL (473 mL)
Tablet, Oral:
Zovirax: 400 mg
Zovirax: 800 mg [contains fd&c blue #2 (indigotine)]
Generic: 400 mg, 800 mg
Stable in D5W, NS.
Incompatible with blood products and protein-containing solutions.
Y-site administration: Incompatible with amifostine, amsacrine, aztreonam, caffeine citrate, cefepime, cyclosporine, dobutamine, dopamine, fludarabine, foscarnet, gemcitabine, idarubicin, levofloxacin, ondansetron, pantoprazole, piperacillin/tazobactam, sargramostim, TrophAmine ‚ ®, vinorelbine.
Foscarnet: May enhance the nephrotoxic effect of Acyclovir-Valacyclovir. Avoid combination
Mycophenolate: Acyclovir-Valacyclovir may increase the serum concentration of Mycophenolate. Mycophenolate may increase the serum concentration of Acyclovir-Valacyclovir. Monitor therapy
Talimogene Laherparepvec: Antiherpetic Antivirals may diminish the therapeutic effect of Talimogene Laherparepvec. Monitor therapy
Tenofovir Products: Acyclovir-Valacyclovir may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Acyclovir-Valacyclovir. Monitor therapy
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification
Varicella Virus Vaccine: Acyclovir-Valacyclovir may diminish the therapeutic effect of Varicella Virus Vaccine. Management: When possible, avoid use of acyclovir or valacyclovir within the 24 hours prior to administration of the varicella vaccine, and avoid use of these antiviral agents for 14 days after vaccination. Avoid combination
Zidovudine: Acyclovir-Valacyclovir may enhance the CNS depressant effect of Zidovudine. 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. Avoid combination
Urinalysis, BUN, serum creatinine, liver enzymes, CBC
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
Total body clearance and half-life are dependent on renal function.
Increased plasma concentrations.
Concerns related to adverse effects:
- Renal effects: Renal failure (sometimes fatal) has been reported. Dehydration, preexisting 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 preexisting 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 IV 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.
B
Teratogenic effects were not observed in animal reproduction studies. Acyclovir has been shown to cross the human placenta (Henderson 1992). 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. Acyclovir is recommended for the treatment of genital herpes in pregnant women (CDC [Workowski 2015]).
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.
Oral: 15% to 30%
Vd: Neonates to 3 months of age: 28.8 L/1.73 m2; Children 1 to 2 years: 31.6 L/1.73 m2; Children 2 to 7 years: 42 L/1.73 m2; Adults: 0.8 L/kg (63.6 L). Widely (eg, brain, kidney, lungs, liver, spleen, muscle, uterus, vagina, CSF); CSF acyclovir concentration is 50% of serum concentration
Converted by viral enzymes to acyclovir monophosphate, and further converted to diphosphate then triphosphate (active form) by cellular enzymes
Urine (62% to 90% as unchanged drug and metabolite)
Serum: Oral: Within 1.5 to 2 hours
Terminal: Neonates: 4 hours; Children 1 to 12 years: 2 to 3 hours; Adults: 2 to 3.5 hours (with normal renal function); hemodialysis: ~5 hours
<9% to 33%
- 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 nausea, vomiting, dizziness, fatigue, loss of strength and energy, or injection site irritation. Have patient report immediately to prescriber behavioral changes, mood changes, confusion, hallucinations, seizures, tremors, signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), or signs of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (bruising or bleeding; severe loss of strength and energy; dark urine or jaundice; pale skin; change in the amount of urine passed; vision changes; change in strength on one side is greater than the other; difficulty speaking or thinking; change in balance; or fever) (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.