Acyclovir (Systemic)

Name: Acyclovir (Systemic)

Index Terms

  • Aciclovir
  • ACV
  • Acycloguanosine
  • Acyclovir Sodium
  • Zovirax

Pharmacologic Category

  • Antiviral Agent

Special Populations Renal Function Impairment

Total body clearance and half-life are dependent on renal function.

Use Labeled Indications

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.

Dosing Adult

Bell's palsy (off-label use; alternate therapy): Oral: 2,000 mg/day in divided doses for 10 days in combination with corticosteroids (Gronseth 2012)

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:

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, 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 valacyclovir 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)

Adults ≥40 kg:

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): Adults ≥40 kg: 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): Adults ≥40 kg: 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])

Warnings/Precautions

Concerns related to adverse effects:

• CNS effects: Neurotoxicity (eg, tremor/myoclonus, confusion, agitation, lethargy, hallucination, impaired consciousness) has been reported; risk may be increased with higher doses and in patients with renal failure. Monitor patients for signs/symptoms of neurotoxicity; ensure appropriate dosage reductions in patients with renal impairment (Chowdhury 2016).

• 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.

• Thrombotic microangiopathy: Has been reported in immunocompromised patients receiving acyclovir.

Disease-related concerns:

• Renal impairment: Use with caution; dosage adjustment recommended. Neurotoxicity may be more common in patients with renal impairment (Chowdhury 2016).

• 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.

Pregnancy Risk Factor B Pregnancy Considerations

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]).

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 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.

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