Zovirax

Nucleoside and Nucleotide DNA Polymerase Inhibitor Antivirals
Topical Antivirals

May be administered without regard to meals.

Buccal tablet:
With a dry finger, remove the tablet out of the blister. 
On the same side of the mouth as the herpes labialis symptoms, immediately apply the rounded side of the tablet to the upper gum above the incisor tooth (canine fossa). Hold the tablet in place with slight pressure for 30 seconds.
Once adhered, the tablet will gradually dissolve. Do not crush, chew, suck, or swallow the tablet.
If adhesion does not occur or the tablet falls off within the first 6 hours, immediately reposition the same tablet. If the tablet cannot be repositioned, a new tablet should be applied.
If the tablet is swallowed within the first 6 hours, instruct the patient to drink a glass of water and apply a new tablet.
If the tablet falls or is swallowed after the first 6 hours, reapplication is not needed.

Shake the suspension well prior to administration. Measure the suspension with a calibrated oral dosing device to give accurate dosage.[28977]

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Reconstitution
Reconstitute 500 mg or 1 g vial with 10 or 20 mL, respectively, of sterile water for injection (preservative-free) to give a concentration of 50 mg/mL. Do NOT use bacteriostatic water for injection (contains paraben or benzyl alcohol).
Further dilution is required prior to administration.
Storage: Use reconstituted solutions within 12 hours. Do NOT refrigerate. Refrigeration may result in the formation of a precipitate, which will re-dissolve at room temperature.[34408]
 
Dilution
Withdraw appropriate dose of reconstituted solution and dilute with a compatible IV infusion solution (refer to the manufacturer's guidance for specific compatible solutions).[34408]
Final concentrations for infusion should be 7 mg/mL or less. Higher concentrations (e.g., 10 mg/mL) are associated with phlebitis or injection site reactions.[34408]
Institute for Safe Medication Practices (ISMP)/Vermont Oxford Network (VON) Recommended Standard Concentration for Neonatal Administration: 7 mg/mL [51889]
Storage: Once appropriately diluted, administer the dose within 24 hours. Store the diluted infusion solution at room temperature, 15 to 25 degrees C (59 to 77 degrees F). If refrigerated, a precipitate may form, which will dissolve once warmed to room temperature.[34408]
 
Intermittent IV Infusion
Infuse slowly IV over at least 1 hour to minimize the risk of adverse reactions.
Monitor IV site for signs of phlebitis.[34408]

Do not apply the topical ointment or cream to the eye.
Use a finger cot or rubber glove when applying to avoid transmission of the virus to other sites or persons.
Wash hands thoroughly after administration.

coma / Early / 1.0-1.0
seizures / Delayed / 1.0-1.0
renal tubular obstruction / Delayed / Incidence not known
azotemia / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
tissue necrosis / Early / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
hemolytic-uremic syndrome / Delayed / Incidence not known
thrombotic thrombocytopenic purpura (TTP) / Delayed / Incidence not known
visual impairment / Early / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
vasculitis / Delayed / Incidence not known
disseminated intravascular coagulation (DIC) / Delayed / Incidence not known

phlebitis / Rapid / 9.0-9.0
elevated hepatic enzymes / Delayed / 1.0-2.0
hallucinations / Early / 1.0-1.0
confusion / Early / 1.0-1.0
encephalopathy / Delayed / 1.0-1.0
erythema / Early / 1.0-1.0
anemia / Delayed / 0-1.0
thrombocytopenia / Delayed / 0-1.0
neutropenia / Delayed / 0-1.0
thrombocytosis / Delayed / 0-1.0
stomatitis / Delayed / 1.0-1.0
crystalluria / Delayed / Incidence not known
delirium / Early / Incidence not known
ataxia / Delayed / Incidence not known
psychosis / Early / Incidence not known
dysarthria / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
contact dermatitis / Delayed / Incidence not known
edema / Delayed / Incidence not known
peripheral edema / Delayed / Incidence not known
hypotension / Rapid / Incidence not known
hemolysis / Early / Incidence not known
leukopenia / Delayed / Incidence not known
hematuria / Delayed / Incidence not known
lymphadenopathy / Delayed / Incidence not known

skin irritation / Early / 1.0-30.0
malaise / Early / 11.5-11.5
injection site reaction / Rapid / 9.0-9.0
nausea / Early / 2.4-7.0
vomiting / Early / 2.7-7.0
pruritus / Rapid / 1.0-4.0
diarrhea / Early / 2.4-3.2
headache / Early / 2.2-3.0
rash / Early / 1.0-2.0
lethargy / Early / 1.0-1.0
tremor / Early / 1.0-1.0
dizziness / Early / 1.0-1.0
agitation / Early / 1.0-1.0
leukocytosis / Delayed / 0-1.0
drowsiness / Early / Incidence not known
paresthesias / Delayed / Incidence not known
fatigue / Early / Incidence not known
abdominal pain / Early / Incidence not known
anorexia / Delayed / Incidence not known
alopecia / Delayed / Incidence not known
photosensitivity / Delayed / Incidence not known
xerosis / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
fever / Early / Incidence not known
myalgia / Early / Incidence not known

Sitavig, Zovirax, Zovirax Cream, Zovirax Ointment, Zovirax Powder, Zovirax Suspension

Rx

Synthetic antiviral with activity against herpes simplex virus type 1 and 2 and varicella-zoster virus
Used to treat herpes labialis, herpes genitalis, herpes simplex encephalitis, herpes simplex keratitis, neonatal herpes infection, chickenpox (varicella), shingles (zoster)
Potent activity against herpes simplex viruses type 1 and 2 and much less activity against varicella-zoster virus

400 mg PO 3 times daily for 7 to 10 days or until clinical resolution. The FDA-approved dosage is 200 mg PO every 4 hours, 5 times daily for 10 days.

400 mg PO 3 times daily for 7 to 10 days or until clinical resolution. 

40 to 80 mg/kg/day (Max: 1,200 mg/day) PO in 3 to 4 divided doses for 7 to 10 days or until clinical resolution.

5 mg/kg/dose IV every 8 hours for 5 days. The FDA-approved labeling recommends using ideal body weight when dosing obese adult patients.

5 mg/kg/dose IV every 8 hours for 5 days. The FDA-approved labeling recommends using ideal body weight when dosing obese adults. Similar considerations should be given to pediatric patients.

400 mg PO 3 times daily for 7 to 10 days or until clinical resolution. The duration of therapy may be extended if healing is incomplete by day 10. The FDA-approved dosage is 200 mg PO every 4 hours, 5 times daily for 10 days.

400 mg PO 3 times daily for 7 to 10 days or until clinical resolution.

5 mg/kg/dose IV every 8 hours. Once lesions begin to regress, a change to oral dosing is recommended.[34362] The FDA-approved labeling recommends using ideal body weight when dosing obese adult patients.

5 mg/kg/dose IV every 8 hours. Once lesions begin to regress, a change to oral dosing is recommended.[34362] The FDA-approved labeling recommends using ideal body weight when dosing obese adult patients. Similar considerations should be given to pediatric patients.

Apply sufficient quantity of ointment to adequately cover all lesions every 3 hours, 6 times daily, for 7 days. The dose size per application will vary depending upon the lesion area but should approximate 0.5-inch ribbon of ointment per 4 square inches of surface area. Treatment should begin at the first sign or symptom.

800 mg PO 3 times daily for 2 days or 800 mg PO twice daily for 5 days. Treatment should begin at the first sign or symptom, either during the prodrome or within 1 day of lesion onset. The FDA-approved dosage is 200 mg PO every 4 hours, 5 times daily, for 5 days.

800 mg PO 3 times daily for 2 days or 800 mg PO twice daily for 5 days. Treatment should begin at the first sign or symptom, either during the prodrome or within 1 day of lesion onset.

400 mg PO 3 times daily for 5 to 10 days. Treatment should begin at the first sign or symptom, either during the prodrome or within 1 day of lesion onset. The FDA-approved dosage is 200 mg PO every 4 hours, 5 times daily, for 5 days, initiated at the first sign or symptom or recurrence.

400 mg PO 3 times daily for 5 to 10 days. Treatment should begin at the first sign or symptom, either during the prodrome or within 1 day of lesion onset.

400 mg PO 3 times daily for 5 to 10 days or until clinical resolution.

400 mg PO 3 times daily for 5 to 10 days or until clinical resolution.

20 mg/kg/dose (Max: 400 mg/dose) PO 4 times daily for 7 to 10 days or until clinical resolution for mild symptomatic gingivostomatitis.

5 mg/kg/dose IV every 8 hours for 7 days. Once lesions begin to regress, a change to oral dosing is recommended. [34408] The FDA-approved labeling recommends the use of ideal body weight when dosing obese adult patients.[34408]

5 mg/kg/dose IV every 8 hours for 7 days. Once lesions begin to regress, a change to oral dosing is recommended. [34408] The FDA-approved labeling recommends the use of ideal body weight when dosing obese adult patients.[34408] Similar considerations should be given to pediatric patients.

5 to 10 mg/kg/dose IV every 8 hours for 7 days. Once lesions begin to regress, a change to oral dosing is recommended. The FDA-approved labeling recommends the use of ideal body weight when dosing obese adult patients.[34408] Similar considerations should be given to pediatric patients.

Apply a sufficient quantity of ointment to adequately cover all lesions every 3 hours, 6 times daily, for 7 days. The dose size per application will vary depending upon the lesion area but should be approximately 0.5-inch ribbon of ointment per 4 square inches of surface area. Therapy should be initiated as early as possible after signs and symptoms onset.

Apply sufficient quantity of cream to cover the lesions 5 times daily for 4 days. Treatment should begin at the first sign or symptom (during the prodrome or when lesions appear).[43519]

Apply sufficient quantity of cream to cover the lesions 5 times daily for 4 days. Treatment should begin at the first sign or symptom (during the prodrome or when lesions appear).[43519]

One 50-mg buccal tablet applied to the upper gum region as a single dose.

400 mg PO 5 times daily for 5 days.

20 mg/kg/dose (Max: 400 mg/dose) PO 4 times daily for 5 to 7 days.

400 mg PO 3 times daily for 5 to 10 days.

20 mg/kg/dose (Max: 400 mg/dose) PO 4 times daily for 5 to 7 days.

20 mg/kg/dose IV every 8 hours. For neonates born to mothers with no history of genital HSV preceding pregnancy, acyclovir should be initiated by 24 hours of age prior to HSV virology testing results. Acyclovir therapy may be discontinued if virology studies are negative. If virology studies are positive, or it is a first episode of primary or nonprimary maternal genital herpes infection, continue acyclovir for 10 days. For neonates born to mothers with a maternal history of genital HSV preceding pregnancy, acyclovir should be initiated for neonates with positive virology studies and continued for 10 days.

20 mg/kg/dose IV every 8 hours for 14 days, followed by oral acyclovir suppressive therapy for 6 months.

20 mg/kg/dose IV every 8 hours for 14 days, followed by oral acyclovir suppressive therapy for 6 months.

20 mg/kg/dose IV every 8 hours for 14 days, followed by oral acyclovir suppressive therapy for 6 months. The FDA-approved dose is 20 mg/kg/dose IV every 12 hours.

20 mg/kg/dose IV every 8 hours for 21 days, followed by oral acyclovir suppressive therapy for 6 months. If evidence of CNS disease is present at the initiation of therapy, repeat cerebrospinal fluid (CSF) HSV polymerase chain reaction (PCR) near the end of the 21-day treatment course. If positive, continue acyclovir for 7 additional days. Repeat CSF HSV PCR again near the anticipated end of the treatment course to determine whether cessation of therapy is appropriate.

20 mg/kg/dose IV every 8 hours for 21 days, followed by oral acyclovir suppressive therapy for 6 months. If evidence of CNS disease is present at the initiation of therapy, repeat cerebrospinal fluid (CSF) HSV polymerase chain reaction (PCR) near the end of the 21-day treatment course. If positive, continue acyclovir for 7 additional days. Repeat CSF HSV PCR again near the anticipated end of the treatment course to determine whether cessation of therapy is appropriate.

20 mg/kg/dose IV every 8 hours for 21 days, followed by oral acyclovir suppressive therapy for 6 months. The FDA-approved dose is 20 mg/kg/dose IV every 12 hours. If evidence of CNS disease is present at the initiation of therapy, repeat cerebrospinal fluid (CSF) HSV polymerase chain reaction (PCR) near the end of the 21-day treatment course. If positive, continue acyclovir for 7 additional days. Repeat CSF HSV PCR again near the anticipated end of the treatment course to determine whether cessation of therapy is appropriate.

400 mg PO twice daily. In persons living with HIV, guidelines suggest suppressive therapy may be continued indefinitely (without regard to CD4 count). A review of the continued need should be conducted annually. Alternative regimens have ranged from 200 mg PO 3 times daily to 200 mg PO 5 times daily.

400 mg PO twice daily. In persons living with HIV, guidelines suggest suppressive therapy may be continued indefinitely (without regard to CD4 count). A review of the continued need should be conducted annually. Alternative regimens have ranged from 200 mg PO 3 times daily to 200 mg PO 5 times daily.

20 mg/kg/dose (Max: 400 mg/dose) PO twice daily is recommended for persons living with HIV. After a prolonged period (e.g., 1 year) of prophylaxis, consider stopping prophylaxis and assess patient to determine if additional prophylaxis is required. Although level of immune reconstitution should be a consideration, specific CD4 thresholds have not been determined.

NOTE: For congenital herpes, see neonatal herpes simplex virus infection.

10 mg/kg/dose IV every 8 hours for 14 to 21 days.[34213] Use ideal body weight when dosing persons with obesity.[34408]

10 mg/kg/dose IV every 8 hours for 14 to 21 days.[34213] In persons living with HIV, treat for 21 days.[34361] Use ideal body weight when dosing persons with obesity.[34408]

10 to 15 mg/kg/dose IV every 8 hours for 14 to 21 days.[34213] In persons living with HIV, treat for 21 days.[34361] The FDA-approved dose is 20 mg/kg/dose IV every 8 hours for 10 days.[34408] Use ideal body weight when dosing persons with obesity.[34408]

20 mg/kg/dose IV every 8 hours for 21 days.

10 to 15 mg/kg/dose IV every 8 hours for 10 to 14 days.[34213] Use ideal body weight when dosing persons with obesity.[34408]

10 to 15 mg/kg/dose IV every 8 hours for 10 to 14 days.[34213] Use ideal body weight when dosing persons with obesity.[34408]

20 mg/kg/dose IV every 8 hours for 10 to 14 days.

12.5 to 15 mg/kg/dose IV every 8 hours for 10 to 14 days.[34213] Use ideal body weight when dosing persons with obesity.[34408]

10 mg/kg/dose IV every 8 hours. Use ideal body weight when dosing persons with obesity.[34408]

10 mg/kg/dose IV every 8 hours. Use ideal body weight when dosing persons with obesity.[34408]

20 mg/kg/dose IV every 8 hours.

20 mg/kg/dose IV every 8 hours.

10 mg/kg/dose IV every 8 hours for 7 to 10 days.[34408] For persons living with HIV and extensive cutaneous lesions or visceral involvement, guidelines recommend 10 mg/kg/dose IV every 8 hours until clinical improvement, followed up by oral therapy (including acyclovir, famciclovir, or valacyclovir) to complete a 10- to 14-day course.[34362] The FDA-approved labeling recommends using ideal body weight when dosing obese adult patients.[34408]

10 mg/kg/dose IV every 8 hours for 7 to 10 days.[34408] For persons living with HIV and extensive cutaneous lesions or visceral involvement, guidelines recommend 10 mg/kg/dose IV every 8 hours until clinical improvement, followed up by oral therapy (including acyclovir, famciclovir, or valacyclovir) to complete a 10- to 14-day course.[34362] The FDA-approved labeling recommends the use of ideal body weight when dosing obese adult patients.[34408] Similar consideration should be given to pediatric patients.

10 mg/kg/dose IV every 8 hours for 7 to 10 days. The FDA-approved dosage regimen is 20 mg/kg/dose IV every 8 hours for 7 to 10 days.[34408] For persons living with HIV and trigeminal nerve involvement or extensive multi-dermatomal zoster, guidelines recommend treating with 10 mg/kg/dose IV every 8 hours until cutaneous lesions and visceral disease are clearly resolving and then switching to oral therapy to complete a 10- to 14-day course.[34361] The FDA-approved labeling recommends the use of ideal body weight when dosing obese adult patients.[34408] Similar consideration should be given to pediatric patients.

800 mg PO 5 times daily for 7 to 10 days.[28977] For localized lesions in persons living with HIV, guidelines recommend as an alternative but suggest that the duration may be longer if the lesions are slow to resolve. For extensive cutaneous lesions or visceral involvement in persons living with HIV, oral acyclovir may be used as stepdown therapy after IV acyclovir to complete 10 to 14 days of therapy.[34362]

800 mg PO 5 times daily for 7 to 10 days is recommended as an alternative therapy for those with uncomplicated disease. Consider longer duration if lesions are slow to resolve. For extensive cutaneous lesions or visceral involvement in persons living with HIV, oral acyclovir may be used as stepdown therapy after IV acyclovir to complete 10 to 14 days of therapy.[34362]

20 mg/kg/dose (Max: 800 mg/dose) PO 4 times daily for 7 to 10 days for uncomplicated disease.[34361]

800 mg PO 5 times daily for 7 to 10 days. Initiate therapy within 48 to 72 hours of rash onset. During trials, therapy was begun within 72 hours of rash onset and was most effective if started within the first 48 hours. Adults older than 50 years showed the greatest benefit.

800 mg PO 5 times daily for 5 to 7 days.

10 mg/kg IV every 8 hours for 7 to 10 days. The use of ideal body weight is recommended when dosing obese adults.[34408]

10 mg/kg/dose or 500 mg/m2/dose IV every 8 hours for 7 to 10 days. The use of ideal body weight is recommended when dosing obese adults.[34408] Similar consideration should be given to pediatric patients.

10 mg/kg/dose IV every 8 hours for 7 to 10 days.

800 mg PO 4 times daily for 5 days. Initiate therapy at the first sign of symptoms (i.e., within 24 hours).

20 mg/kg/dose (Max: 800 mg/dose) PO 4 times daily for 5 days. Initiate therapy at the first sign of symptoms (i.e., within 24 hours). In general, acyclovir is not recommended for routine use for the treatment of varicella infections in otherwise healthy children at low risk for complications; consider for those at increased risk of moderate to severe varicella.[28977]

NOTE: Intravenous acyclovir is recommended for those with severe infection requiring hospitalization, including pregnant patients.

10 mg/kg/dose or 500 mg/m2/dose IV every 8 hours for 7 to 10 days. The FDA-approved labeling recommends the use of ideal body weight when dosing obese adult patients.

10 mg/kg/dose or 500 mg/m2/dose IV every 8 hours for 7 to 10 days. The FDA-approved labeling recommends the use of ideal body weight when dosing obese adult patients.[34408] Similar consideration should be given to pediatric patients.

10 mg/kg/dose IV every 8 hours for 7 to 10 days for severe or complicated infections. May switch to oral therapy after defervescence if there is no evidence of visceral involvement. The FDA-approved labeling recommends the use of ideal body weight when dosing obese adult patients.

10 mg/kg/dose IV every 8 hours for 7 to 10 days for severe or complicated infections. May switch to oral therapy after defervescence if there is no evidence of visceral involvement. The FDA-approved labeling recommends the use of ideal body weight when dosing obese adult patients.[34408] Similar consideration should be given to pediatric patients.

10 mg/kg/dose or 500 mg/m2/dose IV every 8 hours for 7 to 10 days and until there are no new lesions for 48 hours for severe or complicated infections or for those with severe immunosuppression.[34361] The FDA-approved labeling recommends the use of ideal body weight when dosing obese adult patients.[34408] Similar consideration should be given to pediatric patients.

10 mg/kg/dose IV every 8 hours for 7 to 10 days and until there are no new lesions for 48 hours for severe or complicated infections or for those with severe immunosuppression.

10 to 20 mg/kg/dose IV every 8 hours.

NOTE: Due to poor bioavailability, experts generally recommend against the use of oral acyclovir for varicella infections in immunocompromised patients.

800 mg PO 5 times daily for 5 to 7 days in uncomplicated infections.[34362] The FDA-approved dosage is 800 mg PO 4 times daily for 5 days. Initiate therapy at the first sign of symptoms (i.e., within 24 hours).[28977]

800 mg PO 5 times daily for 5 to 7 days in uncomplicated infections.[34362] The FDA-approved dosage is 800 mg PO 4 times daily for 5 days. Initiate therapy at the first sign of symptoms (i.e., within 24 hours).[28977]

20 mg/kg/dose (Max: 800 mg/dose) PO 4 times per day for 7 to 10 days and until there are no new lesions for 48 hours. For persons living with HIV, oral acyclovir should only be used for children who are in CDC Immunologic Category 1 or 2 (no or moderate immune suppression) and who have mild varicella disease.[34361] The FDA-approved duration is 5 days. Initiate therapy at the first sign of symptoms (i.e., within 24 hours).[28977]

20 mg/kg/dose PO 4 times daily for 7 to 10 days and until there are no new lesions for 48 hours. For persons living with HIV, oral acyclovir should only be used for children who are in CDC Immunologic Category 1 or 2 (no or moderate immune suppression) and who have mild varicella disease. Initiate at first sign of symptoms (i.e., within 24 hours).[34361]

800 mg PO 5 times daily for a total treatment course of 7 to 10 days.

800 mg PO 5 times daily for a total treatment course of 7 to 10 days.

400 mg PO 3 times daily following IV therapy to complete at least 10 days of total therapy or until lesions are completely healed.

400 mg PO 3 times daily following IV therapy to complete at least 10 days of total therapy or until lesions are completely healed.

1,000 mg/day PO divided into 3 to 5 doses following IV therapy to complete at least 10 days of total therapy or until lesions are completely healed.

5 to 10 mg/kg/dose IV every 8 hours for at least 7 days or until clinical improvement, then oral antiviral therapy to complete at least 10 days of total therapy or until lesions are completely healed.[34408] The FDA-approved labeling recommends using ideal body weight when dosing obese adult patients.[34408]

5 to 10 mg/kg/dose IV every 8 hours for at least 7 days or until clinical improvement, then oral antiviral therapy to complete at least 10 days of total therapy or until lesions are completely healed. [34408] The FDA-approved labeling recommends using ideal body weight when dosing obese adult patients.[34408] Similar consideration should be given to pediatric patients.

10 mg/kg/dose IV every 8 hours for at least 7 days or until clinical improvement, then oral antiviral therapy to complete at least 10 days of total therapy or until lesions are completely healed. [34408] For disseminated disease in persons living with HIV, 10 to 15 mg/kg/dose IV every 8 hours for 21 days is recommended.[34361] The FDA-approved labeling recommends the use of ideal body weight when dosing obese adult patients.[34408] Similar consideration should be given to pediatric patients.

10 mg/kg/dose IV every 8 hours for at least 7 days or until clinical improvement, then oral antiviral therapy to complete at least 10 days of total therapy or until lesions are completely healed. [34408] For disseminated disease in persons living with HIV, 10 to 15 mg/kg/dose IV every 8 hours for 21 days is recommended.[34361]

800 mg PO 5 times daily for 7 to 10 days. Initiate therapy within 48 to 72 hours of rash onset. Guidelines recommend famciclovir or valacyclovir.

800 mg PO 5 times daily for 7 to 10 days. Initiate therapy within 48 to 72 hours of rash onset.   Guidelines recommend famciclovir or valacyclovir.

NOTE: Intravenous acyclovir therapy is recommended for those with retinitis.

10 mg/kg/dose IV every 8 hours for 7 to 10 days. Transition to oral antiviral therapy when infection is controlled for remainder of 7- to 10-day treatment course.

10 mg/kg/dose IV every 8 hours for 7 to 10 days.  Transition to oral antiviral therapy when infection is controlled for remainder of 7- to 10-day treatment course.

NOTE: Oral therapy can be considered for those who are not severely immunosuppressed.

800 mg PO 5 times daily for 7 to 14 days. Initiate therapy within 48 to 72 hours of rash onset.    Guidelines recommend famciclovir or valacyclovir.

800 mg PO 5 times daily for 7 to 14 days. Initiate therapy within 48 to 72 hours of rash onset.   Guidelines recommend famciclovir or valacyclovir.

10 mg/kg/dose IV every 8 hours for 7 to 14 days.  Transition to oral antiviral therapy when infection is controlled for remainder of 7- to 14-day treatment course.

10 mg/kg/dose IV every 8 hours for 7 to 14 days.  Transition to oral antiviral therapy when infection is controlled for remainder of 7- to 14-day treatment course.

400 mg PO twice daily. Suppressive therapy may be continued indefinitely (without regard to CD4 count). A review of the continued need should be conducted annually.

400 mg PO twice daily. Suppressive therapy may be continued indefinitely (without regard to CD4 count). A review of the continued need should be conducted annually.

20 mg/kg/dose (Max: 400 mg/dose) PO twice daily. After a prolonged period (e.g., 1 year) of prophylaxis, consider stopping prophylaxis and assess patient to determine if additional prophylaxis is required. Although level of immune reconstitution should be a consideration, specific CD4 thresholds have not been determined.[34361]

300 mg/m2/dose PO 3 times daily for 6 months after initial treatment with IV acyclovir.[51746] The dose should be adjusted each month for growth. Absolute neutrophil counts should be assessed 2 to 4 weeks after suppressive therapy start and then monthly thereafter during treatment.

400 to 800 mg PO twice daily to prevent early reactivation or 800 mg PO twice daily to prevent late reactivation; administer during the period of risk. For prevention of early reactivation in HCT recipients, initiate therapy beginning 1 day prior to transplant and continue until marrow engraftment. For prevention of late reactivation among HCT recipients, treat during the first year after HCT.

80 mg/kg/day (Max: 1,600 mg/day) PO in 2 to 3 divided doses during the period of risk. For prevention of early reactivation in HCT recipients, initiate therapy beginning 1 day prior to transplant and continue until marrow engraftment. For prevention of late reactivation among HCT recipients, treat during the first year after HCT.

250 mg/m2/dose or 5 mg/kg/dose IV every 12 hours during the period of risk. For prevention of early reactivation in HCT recipients, initiate therapy beginning 1 day prior to transplant and continue until marrow engraftment. The FDA-approved labeling recommends the use of ideal body weight when dosing obese adult patients.

5 mg/kg/dose IV every 8 hours during the period of risk. For prevention of early reactivation in HCT recipients, initiate therapy beginning 1 day prior to transplant and continue until marrow engraftment. The FDA-approved labeling recommends the use of ideal body weight when dosing obese adult patients.

800 mg PO 5 times daily for 5 to 7 days beginning 7 to 10 days after exposure is recommended by some experts when passive immunization with varicella zoster immunoglobulin (VariZIG) is not feasible; however, this intervention has not been studied in persons living with HIV. Post-exposure prophylaxis is indicated for persons living with HIV who lack evidence of immunity to varicella with substantial exposure to a contact with varicella or herpes zoster.

800 mg PO 5 times daily for 5 to 7 days beginning 7 to 10 days after exposure is recommended by some experts when passive immunization with varicella zoster immunoglobulin (VariZIG) is not feasible; however, this intervention has not been studied in persons living with HIV. Post-exposure prophylaxis is indicated for persons living with HIV who lack evidence of immunity to varicella with substantial exposure to a contact with varicella or herpes zoster.[34362]

20 mg/kg/dose (Max: 800 mg/dose) PO 4 times daily for 7 days beginning 7 to 10 days after exposure is recommended by some experts when passive immunization with varicella zoster immunoglobulin (VariZIG) or IVIG is not feasible. Due to the lack of data for acyclovir prophylaxis in persons living with HIV, other experts consider it prudent to wait until rash appears to begin acyclovir treatment. Post-exposure prophylaxis is indicated for children living with HIV who lack evidence of immunity to varicella with substantial exposure to a contact with varicella or herpes zoster. Some limit this recommendation to children who are severely immunocompromised (i.e., CDC Immunologic Category 3), particularly if also classified as CDC Clinical Category C and experiencing high HIV RNA plasma viral load.

500 mg/m2/dose IV every 8 hours during the period of risk has been used. FDA-approved labeling recommends using ideal body weight when dosing obese adult patients.[28977]

500 mg/m2/dose IV every 8 hours during the period of risk has been used. FDA-approved labeling recommends using ideal body weight when dosing obese adult patients.[28977] Similar consideration should be given to pediatric patients.

500 mg/m2/dose IV every 8 hours. Prophylaxis with acyclovir has been shown to decrease the rate of CMV infection and improve survival in hematopoietic cell transplantation (HSCT) recipients. Acyclovir is considered an alternative to ganciclovir for prophylaxis of CMV infection in HSCT recipients. FDA-approved labeling recommends using ideal body weight when dosing obese adult patients.

500 mg/m2/dose IV every 8 hours.[23936] [56888] [56889] [56898] Prophylaxis with acyclovir has been shown to decrease the rate of CMV infection and improve survival in hematopoietic cell transplantation (HSCT) recipients.[23936] [56888] [56889] Acyclovir is considered an alternative to ganciclovir for prophylaxis of CMV infection in HSCT recipients.[51812] FDA-approved labeling recommends using ideal body weight when dosing obese adult patients.[34408] Similar consideration should be given to pediatric patients.

800 mg PO 4 times per day as an alternative to ganciclovir for prophylaxis of CMV infection in hematopoietic cell transplantation recipients.

800 mg PO 4 times per day as an alternative to ganciclovir for prophylaxis of CMV infection in hematopoietic cell transplantation recipients.

600 mg/m2/dose PO 4 times per day as an alternative to ganciclovir for prophylaxis of CMV infection in hematopoietic cell transplantation recipients.

800 mg PO 6 hours prior to transplantation, followed by 800 mg PO 24 hours after transplantation, followed by 800 mg PO four times per day has been utilized. Dosage was adjusted for patients with compromised renal function. However, guidelines recommend prophylaxis with other agents, including valacyclovir, ganciclovir, and valganciclovir; use of acyclovir has been deemed inferior and, thus, fallen out of favor.

800 mg PO every 6 hours for 20 days was found effective in an open label study of a small number of HIV-positive men. After therapy was discontinued, recurrences developed in all 5 patients who had initially responded.

400 mg PO 5 times daily for 10 days or 800 mg PO 3 times daily for 5 to 10 days in combination with an oral corticosteroid. Clinical practice guidelines suggest an antiviral plus oral corticosteroid within 72 hours of symptom onset to modestly increase probability of functional facial nerve recovery.

400 mg PO 3 to 5 times daily for 7 to 10 days.

400 mg PO 3 times daily for 7 to 10 days.

20 to 80 mg/kg/day (Max: 1,200 mg/day) PO divided 3 times daily for 7 to 10 days.

800 mg PO 5 times daily for 14 to 21 days.

400 mg PO 3 times daily for 14 to 21 days.

20 to 80 mg/kg/day (Max: 1,200 mg/day) PO divided 3 times daily for 14 to 21 days.

400 mg PO twice daily plus topical ophthalmic steroid for at least 10 weeks.

400 mg PO twice daily plus topical ophthalmic steroid for at least 10 weeks, then 400 mg PO twice daily as long-term prophylaxis.

20 to 80 mg/kg/day (Max: 800 mg/day) PO divided twice daily plus topical ophthalmic steroid for at least 10 weeks, then 20 to 80 mg/kg/day (Max: 800 mg/day) PO divided twice daily as long-term prophylaxis.

800 mg PO 3 to 5 times daily for 7 to 10 days plus topical ophthalmic steroid, then 400 mg PO twice daily for the duration of topical ophthalmic steroid use.

400 mg PO 3 times daily for 7 to 10 days plus topical ophthalmic steroid, then 400 mg PO twice daily as long-term prophylaxis.

20 to 80 mg/kg/day (Max: 1,200 mg/day) PO divided 3 times daily for 7 to 10 days plus topical ophthalmic steroid, then 20 to 80 mg/kg/day (Max: 800 mg/day) PO divided twice daily as long-term prophylaxis.

400 to 800 mg PO 3 to 5 times daily for 7 to 10 days plus topical ophthalmic steroid, then 400 mg PO twice daily for the duration of topical ophthalmic steroid use.

400 mg PO 3 times daily for 7 to 10 days plus topical ophthalmic steroid, then 400 mg PO twice daily for the duration of topical ophthalmic steroid use.

20 to 80 mg/kg/day (Max: 1,200 mg/day) PO divided 3 times daily for 7 to 10 days plus topical ophthalmic steroid, then 20 to 80 mg/kg/day (Max: 800 mg/day) PO divided twice daily for the duration of topical ophthalmic steroid use.

400 mg PO twice daily for at least 12 months.

400 mg PO twice daily for at least 12 months.

20 to 80 mg/kg/day (Max: 800 mg/day) PO divided twice daily for at least 12 months.

After initial IV therapy, 20 mg/kg/dose PO 4 times daily for 4 to 6 weeks in patients unable to take valacyclovir.

10 mg/kg/dose IV every 8 hours for 10 to 14 days plus intravitreal ganciclovir injection until evidence of treatment response, then oral valacyclovir for at least 14 weeks. Involvement of an experienced ophthalmologist is recommended. The FDA-approved labeling recommends using ideal body weight when dosing obese adult patients.

10 mg/kg/dose IV every 8 hours for 10 to 14 days plus intravitreal ganciclovir injection until evidence of treatment response, then oral valacyclovir for at least 14 weeks. Involvement of an experienced ophthalmologist is recommended. The FDA-approved labeling recommends using ideal body weight when dosing obese adult patients. Similar consideration should be given to pediatric patients.

10 to 15 mg/kg/dose IV every 8 hours for 10 to 14 days followed by oral therapy with valacyclovir or acyclovir for 4 to 6 weeks. The FDA-approved labeling recommends using ideal body weight when dosing obese adult patients. Similar consideration should be given to pediatric patients.

10 mg/kg/dose IV every 8 hours plus ganciclovir intravitreal injection and/or foscarnet intravitreal injection. The duration of therapy is not wel

10 mg/kg/dose IV every 8 hours plus ganciclovir intravitreal injection and/or foscarnet intravitreal injection. The duration of therapy is not well defined and should be based on clinical, virologic, and immunologic responses in consultation with ophthalmologist. The FDA-approved labeling recommends using ideal body weight when dosing obese adult patients.

10 mg/kg/dose or 500 mg/m2/dose IV every 8 hours plus IV foscarnet plus ganciclovir intravitreal injection and/or foscarnet intravitreal injection. The duration of therapy is not well defined and should be based on clinical, virologic, and immunologic responses in consultation with an ophthalmologist. The FDA-approved labeling recommends using ideal body weight when dosing obese adult patients.

†Indicates off-label use

No dosage adjustment needed.

Non-neonatal Populations
CrCl more than 50 mL/min/1.73 m2: no dosage adjustment needed.
CrCl 26 to 50 mL/min/1.73 m2: extend IV dosing interval to every 12 hours. No adjustment required for oral dosage regimens.
CrCl 11 to 25 mL/min/1.73 m2: extend IV dosing interval to every 24 hours. For patients receiving 800 mg PO 5 times per day, the dosage interval should be extended to every 8 hours. No dosage adjustment is necessary for patients receiving 400 mg PO every 12 hours or 200 mg PO 5 times per day.
CrCl 10 mL/min/1.73 m2 or less: reduce recommended IV dose by 50% and extend dosing interval to every 24 hours. For patients receiving 800 mg PO 5 times per day, reduce dose to 800 mg PO every 12 hours. For patients receiving or 400 mg PO every 12 hours or 200 mg PO 5 times per day, reduce dose to 200 mg PO every 12 hours.
 
Neonates
CrCl more than 50 mL/min/1.73 m2 or serum creatinine less than 0.7 mg/dL: no dosage adjustment needed.
CrCl 25 to 50 mL/min/1.73 m2 or serum creatinine 0.8 to 1.1 mg/dL: extend IV dosing interval to every 12 hours.
CrCl 10 to 24 mL/min/1.73 m2 or serum creatinine 1.2 to 1.5 mg/dL: extend IV dosing interval to every 24 hours.
CrCl less than 10 mL/min/1.73 m2, serum creatinine more than 1.5 mg/dL, or urine output less than 1 mL/kg/hr: reduce recommended IV dose by 50% and extend dosing interval to every 24 hours.
 
Intermittent hemodialysis
For IV dosing, 2.5 to 5 mg/kg/dose IV every 24 hours (based on usual dose of 5 to 10 mg/kg/dose IV every 8 hours, and the assumption of 3 complete hemodialysis sessions/week). Adjust the dosing schedule so that a dose is administered after each dialysis session. For oral dosing, see dosage based on creatinine clearance and adjust the schedule so that a dose is administered after each dialysis session.
 
Continuous renal replacement therapy (CRRT)
Acyclovir is removed by CRRT; however, clearance is significantly affected by the type of renal replacement therapy, filter type, and flow rate. For CVVH, a dose of 5 to 10 mg/kg/dose IV every 24 hours has been recommended. For CVVHD and CVHDF, a dose of 5 to 10 mg/kg/dose IV every 12 to 24 hours has been recommended. Another recommendation in pediatric patients is 10 mg/kg/dose IV every 12 hours, although method of CRRT is not specified. These are general recommendations only and therapy should be individualized based on therapeutic drug monitoring; some patients may require higher doses to optimize therapy.
 
Peritoneal dialysis
For IV dosing, 5 mg/kg/dose IV every 24 hours. Supplemental systemic doses do not appear to be necessary after peritoneal dialysis.
 
PlasmapheresisAdminister IV doses at least 3 hours before plasmapheresis.

Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of acyclovir is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor.
Acetaminophen; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of acyclovir is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of acyclovir is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of acyclovir is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor.
Adefovir: (Moderate) Chronic coadministration of adefovir with nephrotoxic drugs, such as acyclovir, may increase the risk of developing nephrotoxicity, even in patients who have normal renal function.
Aldesleukin, IL-2: (Moderate) Aldesleukin, IL 2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as acyclovir, with Aldesleukin, IL 2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL 2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
Amikacin: (Moderate) Additive nephrotoxicity is possible if systemic aminoglycosides are used with acyclovir. Carefully monitor renal function during concomitant therapy.
Aminoglycosides: (Moderate) Additive nephrotoxicity is possible if systemic aminoglycosides are used with acyclovir. Carefully monitor renal function during concomitant therapy.
Amphotericin B lipid complex (ABLC): (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including acyclovir, may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Dosage reduction may be necessary if renal impairment occurs.
Amphotericin B liposomal (LAmB): (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including acyclovir, may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Dosage reduction may be necessary if renal impairment occurs.
Amphotericin B: (Moderate) Concurrent use of amphotericin B and other nephrotoxic medications, including acyclovir, may enhance the potential for drug-induced renal toxicity. Monitor renal function carefully during concurrent therapy. Dosage reduction may be necessary if renal impairment occurs.
Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can affect renal function, such as acyclovir, as the risk of renal impairment may be increased.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of acyclovir is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor.
Aspirin, ASA; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of acyclovir is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of acyclovir is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor.
Bendamustine: (Major) Consider the use of an alternative therapy if acyclovir treatment is needed in patients receiving bendamustine. Concomitant use of acyclovir may increase bendamustine exposure, which may increase the risk of adverse reactions (e.g., myelosuppression, infection, hepatotoxicity). Bendamustine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for acyclovir or emtricitabine-related adverse events during concomitant use. Concomitant use may increase acyclovir or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as acyclovir and emtricitabine, may increase the risk of adverse reactions. (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as acyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Bupivacaine; Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with acyclovir is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Butalbital; Acetaminophen; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of acyclovir is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of acyclovir is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of acyclovir is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor.
Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of acyclovir is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor.
Caffeine; Sodium Benzoate: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of acyclovir is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor.
Capreomycin: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including acyclovir, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Cidofovir: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as acyclovir, is contraindicated. Acyclovir should be discontinued at least 7 days prior to beginning cidofovir.
Cimetidine: (Minor) Cimetidine may cause a reduction in the clearance of acyclovir. The clinical significance of these pharmacokinetic interactions is unknown; however, no dosage adjustments are recommended for patients with normal renal function.
Cisplatin: (Moderate) Closely monitor renal function if concomitant use with cisplatin and acyclovir is necessary. Cisplatin can cause nephrotoxicity. Acyclovir can cause renal impairment or renal failure, which may be additive when used with cisplatin.
Clindamycin: (Moderate) Concomitant use of acyclovir and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Clofarabine: (Moderate) Concomitant use of clofarabine and acyclovir may result in altered clofarabine levels because both agents are substrates of OAT1 and OCT1. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g., hand and foot syndrome, rash, pruritus) in patients also receiving OAT1 and OCT1 substrates.
Clomipramine: (Moderate) Monitor for an increase in clomipramine-related adverse reactions if concomitant use of acyclovir is necessary; a clomipramine dose reduction may be necessary. Concomitant use may increase clomipramine exposure; clomipramine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor.
Clozapine: (Moderate) Consider a clozapine dose reduction if coadministered with acyclovir and monitor for adverse reactions. A clinically relevant increase in the plasma concentration of clozapine may occur during concurrent use. Clozapine is a CYP1A2 substrate; acyclovir is a weak CYP1A2 inhibitor.
Colistin: (Moderate) Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including acyclovir, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
Cyclosporine: (Moderate) Additive nephrotoxicity can occur if cyclosporine is administered with other nephrotoxic drugs such as acyclovir. Monitor renal function and fluid status carefully.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for acyclovir or emtricitabine-related adverse events during concomitant use. Concomitant use may increase acyclovir or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as acyclovir and emtricitabine, may increase the risk of adverse reactions. (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as acyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Monitor for changes in serum creatinine and phosphorus if tenofovir disoproxil fumarate is administered in combination with nephrotoxic agents, such as acyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with drugs that decrease renal function may increase concentrations of tenofovir. In addition, use with drugs that are also eliminated by active tubular secretion may increase concentrations of the co-administered drug. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate; a majority of the cases occurred in patients who had underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir containing products should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus, and urine glucose and protein.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for acyclovir or emtricitabine-related adverse events during concomitant use. Concomitant use may increase acyclovir or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as acyclovir and emtricitabine, may increase the risk of adverse reactions. (Moderate) Monitor for changes in serum creatinine and phosphorus if tenofovir disoproxil fumarate is administered in combination with nephrotoxic agents, such as acyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with drugs that decrease renal function may increase concentrations of tenofovir. In addition, use with drugs that are also eliminated by active tubular secretion may increase concentrations of the co-administered drug. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate; a majority of the cases occurred in patients who had underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir containing products should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus, and urine glucose and protein.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for changes in serum creatinine and phosphorus if tenofovir disoproxil fumarate is administered in combination with nephrotoxic agents, such as acyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with drugs that decrease renal function may increase concentrations of tenofovir. In addition, use with drugs that are also eliminated by active tubular secretion may increase concentrations of the co-administered drug. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate; a majority of the cases occurred in patients who had underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir containing products should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus, and urine glucose and protein.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for acyclovir or emtricitabine-related adverse events during concomitant use. Concomitant use may increase acyclovir or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as acyclovir and emtricitabine, may increase the risk of adverse reactions. (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as acyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for acyclovir or emtricitabine-related adverse events during concomitant use. Concomitant use may increase acyclovir or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as acyclovir and emtricitabine, may increase the risk of adverse reactions. (Moderate) Monitor for changes in serum creatinine and phosphorus if tenofovir disoproxil fumarate is administered in combination with nephrotoxic agents, such as acyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with drugs that decrease renal function may increase concentrations of tenofovir. In addition, use with drugs that are also eliminated by active tubular secretion may increase concentrations of the co-administered drug. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate; a majority of the cases occurred in patients who had underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir containing products should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus, and urine glucose and protein.
Emtricitabine: (Moderate) Monitor for acyclovir or emtricitabine-related adverse events during concomitant use. Concomitant use may increase acyclovir or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as acyclovir and emtricitabine, may increase the risk of adverse reactions.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for acyclovir or emtricitabine-related adverse events during concomitant use. Concomitant use may increase acyclovir or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as acyclovir and emtricitabine, may increase the risk of adverse reactions. (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as acyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for acyclovir or emtricitabine-related adverse events during concomitant use. Concomitant use may increase acyclovir or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as acyclovir and emtricitabine, may increase the risk of adverse reactions. (Moderate) Monitor for changes in serum creatinine and phosphorus if tenofovir disoproxil fumarate is administered in combination with nephrotoxic agents, such as acyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with drugs that decrease renal function may increase concentrations of tenofovir. In addition, use with drugs that are also eliminated by active tubular secretion may increase concentrations of the co-administered drug. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate; a majority of the cases occurred in patients who had underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir containing products should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus, and urine glucose and protein.
Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for acyclovir or emtricitabine-related adverse events during concomitant use. Concomitant use may increase acyclovir or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as acyclovir and emtricitabine, may increase the risk of adverse reactions. (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as acyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for acyclovir or emtricitabine-related adverse events during concomitant use. Concomitant use may increase acyclovir or emtricitabine concentrations. Coadministration of drugs that reduce renal function or compete for active tubular secretion, such as acyclovir and emtricitabine, may increase the risk of adverse reactions. (Moderate) Monitor for changes in serum creatinine and phosphorus if tenofovir disoproxil fumarate is administered in combination with nephrotoxic agents, such as acyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with drugs that decrease renal function may increase concentrations of tenofovir. In addition, use with drugs that are also eliminated by active tubular secretion may increase concentrations of the co-administered drug. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate; a majority of the cases occurred in patients who had underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir containing products should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus, and urine glucose and protein.
Entecavir: (Moderate) Because entecavir is primarily eliminated by the kidneys and acyclovir can affect renal function, concurrent administration with acyclovir may increase the serum concentrations of entecavir and adverse events. The manufacturer of entecavir recommends monitoring for adverse effects when these drugs are coadministered.
Ergotamine; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of acyclovir is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor.
Ethiodized Oil: (Moderate) Concomitant use of acyclovir and contrast agents should be avoided when possible, as use of these drugs together may increase the risk for nephrotoxicity.
Ethotoin: (Minor) In a single case report, the addition of acyclovir to a regimen of phenytoin and valproate led to a clinically significant decrease in phenytoin serum concentrations and loss of seizure control. Acyclovir did not appear to affect valproate concentrations in this report. Until more data are known, clinicians should be prepared to make adjustments in hydantoin dosing if acyclovir therapy is added or discontinued.
Fezolinetant: (Contraindicated) Concomitant use of fezolinetant and acyclovir is contraindicated due to the risk of increased fezolinetant exposure which may increase the risk of fezolinetant-related adverse effects. Fezolinetant is a CYP1A2 substrate; acyclovir is a weak CYP1A2 inhibitor. Concomitant use with another weak CYP1A2 inhibitor increased fezolinetant overall exposure by 100%.
Foscarnet: (Major) The risk of renal toxicity may be increased if foscarnet is used in conjunction with other nephrotoxic agents, such as acyclovir. Avoid concurrent use, unless the potential benefits outweigh the risks to the patient.
Fosphenytoin: (Minor) In a single case report, the addition of acyclovir to a regimen of phenytoin and valproate led to a clinically significant decrease in phenytoin serum concentrations and loss of seizure control. Acyclovir did not appear to affect valproate concentrations in this report. Until more data are known, clinicians should be prepared to make adjustments in hydantoin dosing if acyclovir therapy is added or discontinued.
Gentamicin: (Moderate) Additive nephrotoxicity is possible if systemic aminoglycosides are used with acyclovir. Carefully monitor renal function during concomitant therapy.
Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like acyclovir. Administer IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. Periodic monitoring of renal function tests and urine output is particularly important in patients judged to have a potential risk for developing acute renal failure.
Hydantoins: (Minor) In a single case report, the addition of acyclovir to a regimen of phenytoin and valproate led to a clinically significant decrease in phenytoin serum concentrations and loss of seizure control. Acyclovir did not appear to affect valproate concentrations in this report. Until more data are known, clinicians should be prepared to make adjustments in hydantoin dosing if acyclovir therapy is added or discontinued.
Immune Globulin IV, IVIG, IGIV: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like acyclovir. Administer IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. Periodic monitoring of renal function tests and urine output is particularly important in patients judged to have a potential risk for developing acute renal failure.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and acyclovir due to the risk of glomerulonephritis and nephrotoxicity.
Iodipamide Meglumine: (Moderate) Concomitant use of acyclovir and contrast agents should be avoided when possible, as use of these drugs together may increase the risk for nephrotoxicity.
Iodixanol: (Moderate) Concomitant use of acyclovir and contrast agents should be avoided when possible, as use of these drugs together may increase the risk for nephrotoxicity.
Iohexol: (Moderate) Concomitant use of acyclovir and contrast agents should be avoided when possible, as use of these drugs together may increase the risk for nephrotoxicity.
Iomeprol: (Moderate) Concomitant use of acyclovir and contrast agents should be avoided when possible, as use of these drugs together may increase the risk for nephrotoxicity.
Ionic Contrast Media: (Moderate) Concomitant use of acyclovir and contrast agents should be avoided when possible, as use of these drugs together may increase the risk for nephrotoxicity.
Iopamidol: (Moderate) Concomitant use of acyclovir and contrast agents should be avoided when possible, as use of these drugs together may increase the risk for nephrotoxicity.
Iopromide: (Moderate) Concomitant use of acyclovir and contrast agents should be avoided when possible, as use of these drugs together may increase the risk for nephrotoxicity.
Ioversol: (Moderate) Concomitant use of acyclovir and contrast agents should be avoided when possible, as use of these drugs together may increase the risk for nephrotoxicity.
Ioxaglate Meglumine; Ioxaglate Sodium: (Moderate) Concomitant use of acyclovir and contrast agents should be avoided when possible, as use of these drugs together may increase the risk for nephrotoxicity.
Isosulfan Blue: (Moderate) Concomitant use of acyclovir and contrast agents should be avoided when possible, as use of these drugs together may increase the risk for nephrotoxicity.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for changes in serum creatinine and phosphorus if tenofovir disoproxil fumarate is administered in combination with nephrotoxic agents, such as acyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with drugs that decrease renal function may increase concentrations of tenofovir. In addition, use with drugs that are also eliminated by active tubular secretion may increase concentrations of the co-administered drug. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate; a majority of the cases occurred in patients who had underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir containing products should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus, and urine glucose and protein.
Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with acyclovir is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Lidocaine; Epinephrine: (Moderate) Monitor for lidocaine toxicity if coadministration with acyclovir is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Lidocaine; Prilocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with acyclovir is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor. Coadministration of another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Lithium: (Moderate) Consider starting with a lower lithium dose and monitor lithium concentrations and for signs and symptoms of lithium toxicity during concomitant acyclovir use. The risk of lithium toxicity is increased with concomitant use of medications that affect kidney function, such as acyclovir.
Mannitol: (Major) Avoid use of mannitol and acyclovir, if possible. Concomitant administration of nephrotoxic drugs, such as acyclovir, increases the risk of renal failure after administration of mannitol.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) If possible, discontinue acyclovir at least 24 hours before administration of the varicella-zoster virus vaccine, live. In patients with HIV, guidelines recommend waiting at least 72 hours after the last dose of acyclovir before administering varicella vaccines. Also, do not administer acyclovir for at least 14 days after vaccination. Concurrent administration of any of the varicella-zoster virus vaccines (Zostavax, Varivax, ProQuad) with antiviral medications known to be effective against varicella zoster virus has not been evaluated. Therefore, when possible, a washout period between the use of the antiviral medication and the vaccines is recommended. Acyclovir has a relatively short serum half-life and is quickly cleared from the body. Refer to the most recent Center for Disease control guidance if concurrent use is necessary.
Methotrexate: (Moderate) Avoid concomitant use of methotrexate with acyclovir due to the risk of additive nephrotoxicity as well as an increased risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions. Acyclovir and methotrexate are both nephrotoxic drugs; methotrexate is also renally eliminated. Coadministration of methotrexate with acyclovir may result in decreased renal function as well as increased methotrexate plasma concentrations.
Mexiletine: (Moderate) Monitor for increased toxicity of mexiletine if coadministered with acyclovir. Coadministration may increase serum concentrations of mexiletine. Mexiletine is a CYP1A2 substrate and acyclovir is a weak CYP1A2 inhibitor.
Mycophenolate: (Moderate) Coadministration of mycophenolate mofetil and acyclovir to healthy volunteers resulted in no significant change in mycophenolic acid concentrations or AUC. However, the glucuronide metabolite of mycophenolate (MPAG) and acyclovir AUCs were increased 10.6% and 21.9%, respectively. Because MPAG and acyclovir concentrations are increased in the presence of renal impairment, the potential exists for the two drugs to compete for tubular secretion, further increasing the concentration of both drugs in patients renal dysfunction.
Non-Ionic Contrast Media: (Moderate) Concomitant use of acyclovir and contrast agents should be avoided when possible, as use of these drugs together may increase the risk for nephrotoxicity.
Nonsteroidal antiinflammatory drugs: (Moderate) Monitor patients for signs of worsening renal function during coadministration of acyclovir and nonsteroidal antiinflammatory drugs. Coadministration may increase the risk for drug-induced nephrotoxicity.
Paromomycin: (Moderate) Additive nephrotoxicity is possible if systemic aminoglycosides are used with acyclovir. Carefully monitor renal function during concomitant therapy.
Phenytoin: (Minor) In a single case report, the addition of acyclovir to a regimen of phenytoin and valproate led to a clinically significant decrease in phenytoin serum concentrations and loss of seizure control. Acyclovir did not appear to affect valproate concentrations in this report. Until more data are known, clinicians should be prepared to make adjustments in hydantoin dosing if acyclovir therapy is added or discontinued.
Pimozide: (Moderate) Monitor for pimozide-related adverse reactions, including QT prolongation and ventricular arrhythmias, if coadministered with acyclovir. Coadministration may result in elevated pimozide concentrations. Pimozide is metabolized primarily through CYP3A, and to a lesser extent CYP1A2 and CYP2D6; acyclovir is a weak CYP1A2 inhibitor.
Plazomicin: (Moderate) Additive nephrotoxicity is possible if systemic aminoglycosides are used with acyclovir. Carefully monitor renal function during concomitant therapy.
Probenecid: (Moderate) Probenecid decreases the renal tubular secretion of acyclovir and can increase serum and CSF concentrations of acyclovir, increasing the potential for toxicity. This interaction would appear to be more significant for parenteral acyclovir.
Probenecid; Colchicine: (Moderate) Probenecid decreases the renal tubular secretion of acyclovir and can increase serum and CSF concentrations of acyclovir, increasing the potential for toxicity. This interaction would appear to be more significant for parenteral acyclovir.
Propafenone: (Moderate) Monitor for increased propafenone toxicity if concomitant use of acyclovir is necessary. Concomitant use may increase propafenone exposure; propafenone is a CYP1A2 substrate and acyclovir is a weak CYP1A2 inhibitor.
Rasagiline: (Moderate) Monitor for dopaminergic adverse effects during concurrent use of rasagiline and acyclovir. Coadministration may result in increased rasagiline concentrations. A dose reduction of rasagiline may be necessary. Rasagiline is primarily metabolized by CYP1A2; acyclovir is a weak CYP1A2 inhibitor.
Streptomycin: (Moderate) Additive nephrotoxicity is possible if systemic aminoglycosides are used with acyclovir. Carefully monitor renal function during concomitant therapy.
Tacrolimus: (Moderate) Tacrolimus, in the absence of overt renal impairment, may adversely affect renal function. Care should be taken in using tacrolimus with other nephrotoxic drugs, including acyclovir. Assessment of renal function in patients who have received tacrolimus is recommended, as the tacrolimus dosage may need to be reduced.
Talimogene Laherparepvec: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
Telavancin: (Moderate) Concurrent or sequential use of telavancin with other potentially nephrotoxic drugs such as acyclovir may lead to additive nephrotoxicity. Closely monitor renal function and adjust telavancin doses based on calculated creatinine clearance.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as acyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with a nephrotoxic agent, such as acyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs, thus, increasing the risk of adverse reactions.
Tenofovir Disoproxil Fumarate: (Moderate) Monitor for changes in serum creatinine and phosphorus if tenofovir disoproxil fumarate is administered in combination with nephrotoxic agents, such as acyclovir. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Concurrent administration with drugs that decrease renal function may increase concentrations of tenofovir. In addition, use with drugs that are also eliminated by active tubular secretion may increase concentrations of the co-administered drug. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate; a majority of the cases occurred in patients who had underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir containing products should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus, and urine glucose and protein.
Theophylline, Aminophylline: (Moderate) Monitor theophylline concentrations and watch for an increase in theophylline-related adverse reactions if coadministration with acyclovir is necessary; a theophylline dose reduction may be necessary. Theophylline is a CYP1A2 substrate with a narrow therapeutic index and acyclovir is a CYP1A2 inhibitor. Coadministration of 320 mg of theophylline with acyclovir 800 mg five times daily increased theophylline AUC 1.4x fold. (Minor) Caution is advised when administering theophylline, aminophylline with acyclovir. Theophylline is primarily metabolized by CYP1A2; acyclovir is a weak inhibitor of CYP1A2. Taking these drugs together may increase the serum concentration of theophylline. Since the therapeutic range of theophylline is narrow, it is prudent to monitor theophylline serum concentrations upon initiation, dosage adjustment, or discontinuation of medications that may alter the function of CYP1A2.
Tizanidine: (Major) Avoid concomitant use of tizanidine and acyclovir as increased tizanidine exposure may occur. If use together is necessary, initiate tizanidine at 2 mg and increase by 2 to 4 mg/day based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. Tizanidine is a CYP1A2 substrate and acyclovir is a weak CYP1A2 inhibitor.
Tobramycin: (Moderate) Additive nephrotoxicity is possible if systemic aminoglycosides are used with acyclovir. Carefully monitor renal function during concomitant therapy.
Vancomycin: (Moderate) Closely monitor renal function if concomitant use with acyclovir and vancomycin is necessary. Both drugs can cause nephrotoxicity, which may be additive when used together.
Varicella-Zoster Virus Vaccine, Live: (Major) If possible, discontinue acyclovir at least 24 hours before administration of the varicella-zoster virus vaccine, live. In patients with HIV, guidelines recommend waiting at least 72 hours after the last dose of acyclovir before administering varicella vaccines. Also, do not administer acyclovir for at least 14 days after vaccination. Concurrent administration of any of the varicella-zoster virus vaccines (Zostavax, Varivax, ProQuad) with antiviral medications known to be effective against varicella zoster virus has not been evaluated. Therefore, when possible, a washout period between the use of the antiviral medication and the vaccines is recommended. Acyclovir has a relatively short serum half-life and is quickly cleared from the body. Refer to the most recent Center for Disease control guidance if concurrent use is necessary.
Voclosporin: (Moderate) Concomitant use of voclosporin and acyclovir may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with acyclovir is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. The R-enantiomer of warfarin is a CYP1A2 substrate and acyclovir is a CYP1A2 inhibitor. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.

Acyclovir/Acyclovir Sodium Intravenous Inj Sol: 1mL, 50mg
Acyclovir/Acyclovir Sodium/Zovirax/Zovirax Powder Intravenous Inj Pwd F/Sol: 500mg
Acyclovir/Zovirax Oral Cap: 200mg
Acyclovir/Zovirax Oral Tab: 400mg, 800mg
Acyclovir/Zovirax/Zovirax Cream Topical Cream: 5%
Acyclovir/Zovirax/Zovirax Ointment Topical Ointment: 5%
Acyclovir/Zovirax/Zovirax Suspension Oral Susp: 5mL, 200mg
Sitavig Buccal Tablet, SL: 50mg

30 mg/kg/day IV per FDA-approved product labeling; however, up to 45 mg/kg/day IV is used off-label; 4,000 mg/day PO; 50 mg/dose buccal.

30 mg/kg/day IV per FDA-approved product labeling; however, up to 45 mg/kg/day IV is used off-label; 4,000 mg/day PO; 50 mg/dose buccal.

30 mg/kg/day IV per FDA-approved product labeling; however, up to 45 mg/kg/day IV is used off-label. 80 mg/kg/day PO (Max: 3,200 mg/day) per FDA-approved product labeling; however, 4,000 mg/day has been used off-label; safety and efficacy of buccal tablet not established.

12 years: 30 mg/kg/day IV per FDA-approved product labeling; however, up to 45 mg/kg/day IV is used off-label; 80 mg/kg/day PO (Max: 3,200 mg/day) per FDA-approved product labeling; however, 4,000 mg/day has been used off-label; safety and efficacy of buccal tablet not established.
2 to 11 years: 60 mg/kg/day IV; 80 mg/kg/day PO (Max: 3,200 mg/day); safety and efficacy of buccal tablet not established.
1 year: 60 mg/kg/day IV; safety and efficacy of oral acyclovir have not been established; however, 80 mg/kg/day PO has been used off-label.

60 mg/kg/day IV; safety and efficacy of oral acyclovir have not been established; however, 80 mg/kg/day PO has been used off-label.

60 mg/kg/day IV; safety and efficacy of oral acyclovir have not been established; however, 900 mg/m2/day PO has been used off-label for suppressive therapy of neonatal herpes.

Acyclovir is a synthetic purine deoxynucleoside analogue with inhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV). Acyclovir inhibits viral DNA synthesis and must be phosphorylated intracellularly to be active. Acyclovir is converted to the monophosphate by viral thymidine kinase (TK), then to diphosphate by cellular guanylate kinase, and finally to the triphosphate by various cellular enzymes. Acyclovir triphosphate stops replication of herpes viral DNA by the following 3 mechanisms: competitive inhibition of viral DNA polymerase, incorporation into and termination of the growing viral DNA chain, and inactivation of the viral DNA polymerase.[28977] [34408] [54268] [63157]
 
Herpes virus DNA polymerases differ in sensitivity to acyclovir. The greater antiviral activity of acyclovir against HSV compared to VZV is due to its more efficient phosphorylation by the viral thymidine kinase. Acyclovir is effective only against actively replicating viruses; therefore, it does not eliminate the latent herpes virus genome. Uninfected cells show only minimal phosphorylation of acyclovir, and there is only a small amount of acyclovir taken up into these cells. The concentration of acyclovir triphosphate is 40- to 100- times higher in HSV-infected cells than non-infected cells.[51534]
 
Resistance to acyclovir by herpes virus results from mutations in viral thymidine kinase and DNA polymerase that cause a loss of thymidine kinase activity, alterations in thymidine kinase (TK) substrate specificity, or decreased DNA polymerase sensitivity. The most common mechanism of resistance is loss of TK activity. Mutations in the viral TK gene may lead to complete loss of TK activity (TK negative), reduced levels of TK activity (TK partial), or alteration in the ability of viral TK to phosphorylate the drug without an equivalent loss in the ability to phosphorylate thymidine (TK altered). These viral variants are also cross resistant to other antiviral agents (e.g., foscarnet, famciclovir, and penciclovir). Thymidine kinase negative variants of herpes virus may cause severe disease in infants and immunocompromised patients. Acyclovir-resistant herpes simplex virus has been seen in immunocompromised patients, patients with concurrent HIV infection, and immunocompetent patients with genital herpes. Repeated systemic treatment may lead to the development of viral resistance in immunosuppressed patients.[28977] [34408] [54268] [63157] [54905]

Acyclovir is administered topically, ophthalmically, orally, buccally, and intravenously. Acyclovir distributes extensively into all tissues, with the highest concentrations in the kidneys, liver, and intestines; acyclovir crosses the placenta. Cerebrospinal fluid (CSF) concentrations are approximately 50% of plasma concentrations.[51529] Acyclovir is poorly protein bound at 9% to 33%; protein binding is independent of plasma acyclovir concentrations.[51536] Excretion is via glomerular filtration and tubular secretion, with approximately 62% to 91% of the drug excreted unchanged.[34408] The only known urinary metabolite is 9-[(carboxy-methoxy)methyl]guanine, which accounts for 8.5% to 14% of the dose in patients with normal renal function. Probenecid decreases acyclovir renal clearance by approximately 32%, presumably by inhibiting tubular secretion of acyclovir.[51529] The elimination half-life of acyclovir in patients with normal renal function is 2.5 to 3.3 hours.[28977] [34408]
 
Affected cytochrome P450 isoenzymes: CYP1A2
Acyclovir is a weak inhibitor of the CYP1A2 isoenzyme. Data on clinical interactions resulting from CYP1A2 inhibition by acyclovir are limited.[56579] [61130]

Acyclovir is poorly absorbed from the GI tract, with an oral bioavailability of 10% to 20%. As the administered dose increases, the bioavailability decreases, resulting in less than dose proportional increase in acyclovir concentrations (e.g., 200 mg Cmax, 0.83 mcg/mL; 400 mg Cmax, 1.21 mcg/mL; 800 mg Cmax, 1.61 mcg/mL). Of note, the decrease in bioavailability is a function of the dose and not the dosage form. Food does not affect the absorption of acyclovir.[28977]

Mean peak acyclovir plasma concentrations have been shown to be directly proportional to the dose administered. After intravenous administration of acyclovir, the mean Cmax in adult patients is 9.8 mcg/mL with 5 mg/kg/dose every 8 hours and 22.9 mcg/mL with 10 mg/kg/dose every 8 hours.

After administration of the topical ointment, 30% to 50% of the drug reaches the basal epidermis in cutaneous infections.[51536] Data suggests systemic absorption of acyclovir after topical application is minimal. Percutaneous absorption of acyclovir 5% ointment was evaluated in 2 clinical pharmacology studies. In the first study, patients were administered a 1-cm strip (25 mg acyclovir) dose 4-times daily for 7 days to an intact skin surface area of 4.5 square inches. After 7 days, a radioimmunoassay (sensitivity, 0.01 mcg/mL) failed to detect any drug in the blood or urine of these patients. In the second study, absorption of acyclovir ointment was evaluated in 11 patients with localized varicella-zoster infections. In this study, acyclovir was identified in the urine of all 11 patients, and in the blood of 9 patients. More specifically, in 8 patients with normal renal function the drug plasma concentrations ranged from less than 0.01 to 0.28 mcg/mL; in 1 patient with impaired renal function, drug concentrations ranged from less than 0.01 to 0.78 mcg/mL. Acyclovir excretion in the urine ranged from less than 0.02% to 9.4% of the daily dose.[51547]

Buccal Route
Buccal administration of a single 50 mg acyclovir dose achieves a mean maximum salivary concentration (Cmax) of 440 +/- 241 mcg/mL approximately 7 hours after application of the tablet, with concentrations declining to 88.1 mcg/mL after 24 hours. Acyclovir concentrations in the plasma are delayed (undetectable at 5 hours) and do not reach levels required for antiviral activity (range: 17.5 to 55.3 ng/mL). The tablet remains adhered for a median duration of 14 hours and, although the effects of food have not been formally studied, patients were allowed to eat and drink during clinical studies.[54268]

No adequate or well-controlled studies have been conducted to evaluate use of acyclovir during human pregnancy; however, published observational studies over decades of acyclovir use have not identified a drug-associated risk of major birth defects, miscarriages, or adverse maternal or fetal outcomes. Further, a prospective epidemiologic registry of acyclovir use during pregnancy was established in 1984 and completed in April 1999. There were 749 pregnancies followed in women exposed to systemic acyclovir during the first trimester of pregnancy resulting in 756 outcomes. The occurrence rate of birth defects approximates that found in the general population. However, the small size of the registry is insufficient to evaluate the risk for specific defects or to permit definitive conclusions regarding the safety of acyclovir in pregnant women. Acyclovir was not found to be teratogenic in standard animal studies. Avoid use of systemic acyclovir during pregnancy unless the potential benefits outweigh the possible risks to the fetus.[28977] [41766] [43519] [54268] Acyclovir is minimally absorbed systemically following topical use. Maternal use is not expected to result in fetal exposure to acyclovir topical cream.

There are no data on the effects of systemic acyclovir on the breastfed child or on milk production. Following oral administration of acyclovir, breast milk concentrations 1- to 4-times that of those found in maternal plasma have been observed.[24464] These concentrations would potentially expose the nursing infant to a dose of acyclovir as high as 0.3 mg/kg/day. Intravenous acyclovir doses of 60 mg/kg/day are used for the treatment of neonatal herpes, and the American Academy of Pediatrics has considered the maternal use of systemic acyclovir to be compatible with breast-feeding.[27500] Although there are no data on the presence of acyclovir in human milk following buccal administration, this route produces low systemic drug exposures. Acyclovir cream is minimally absorbed systemically following topical use, and breast-feeding is not expected to result in exposure of the breastfed child to acyclovir topical cream. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for acyclovir cream and any potential adverse effects on the breastfed child or from the underlying maternal condition.