Name: Acyclovir Injection
- Acyclovir Injection side effects
- Acyclovir Injection drug
- Acyclovir Injection injection
- Acyclovir Injection dosage
- Acyclovir Injection 500 mg
- Acyclovir Injection action
- Acyclovir Injection 15 mg
What special dietary instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What side effects can this medication cause?
Acyclovir injection may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- redness or swelling at the injection site
Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:
- difficulty breathing or swallowing
- swelling of the face, throat, tongue, lips, eyes
Acyclovir injection may cause other side effects. Call your doctor if you have any unusual problems while receiving this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
How to use
What are some things I need to know or do while I take Acyclovir Injection?
- Tell all of your health care providers that you take acyclovir injection. This includes your doctors, nurses, pharmacists, and dentists.
- This medicine is not a cure for herpes infections. Talk with the doctor.
- If you have genital herpes, this medicine will not stop it from spreading. Do not have any kind of sex when you have sores or other signs of genital herpes. Genital herpes can also be spread if you do not have any signs. Do not have any kind of sex without using a latex or polyurethane condom. Talk with your doctor.
- If you are 65 or older, use acyclovir injection with care. You could have more side effects.
- Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
- Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
What are some side effects that I need to call my doctor about right away?
WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
- Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
- Change in the way you act.
- Mood changes.
- Feeling confused.
- Hallucinations (seeing or hearing things that are not there).
- Very bad and sometimes deadly kidney problems have happened with acyclovir injection. Call your doctor right away if you are unable to pass urine or if you have blood in the urine or a change in the amount of urine passed.
- Very bad and sometimes deadly blood problems like thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) have happened with this medicine in some people. Call your doctor right away if you feel very tired or weak or have any bruising or bleeding; dark urine or yellow skin or eyes; pale skin; change in the amount of urine passed; change in eyesight; change in strength on 1 side is greater than the other, trouble speaking or thinking, or change in balance; or fever.
Acyclovir Injection Description
Acyclovir for Injection, USP is a synthetic nucleoside analog, active against herpes viruses. Acyclovir for Injection, USP is a sterile lyophilized powder for intravenous administration only. Each 500 mg vial contains 500 mg of acyclovir and 49 mg of sodium and each 1000 mg vial contains 1000 mg acyclovir and 98 mg of sodium. Reconstitution of the 500 mg or 1000 mg vials with 10 mL or 20 mL, respectively, of Sterile Water for Injection, USP results in a solution containing 50 mg/mL of acyclovir. The pH of the reconstituted solution is approximately 11. Further dilution in any appropriate intravenous solution must be performed before infusion (see DOSAGE AND ADMINISTRATION, Method of Preparation and Administration).
Acyclovir USP is a white to off-white, crystalline powder. Acyclovir sodium is the sodium salt of acyclovir, which is formed in situ, with the molecular formula C8H10N5NaO3 and a molecular weight of 247.19. The maximum solubility in water at 25°C exceeds 100 mg/mL. At physiologic pH, acyclovir sodium exists as the unionized form with a molecular weight of 225 and a maximum solubility in water at 37°C of 2.5 mg/mL. The pka's of acyclovir are 2.27 and 9.25.
The chemical name of acyclovir sodium is 2-amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-6H-purin-6-one monosodium salt; it has the following structural formula:
Mechanism of Antiviral Action
Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV).
The inhibitory activity of acyclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts acyclovir into acyclovir monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. In vitro, acyclovir triphosphate stops replication of herpes viral DNA. This is accomplished in 3 ways: 1) competitive inhibition of viral DNA polymerase, 2) incorporation into and termination of the growing viral DNA chain, and 3) inactivation of the viral DNA polymerase.
The greater antiviral activity of acyclovir against HSV compared to VZV is due to its more efficient phosphorylation by the viral TK.
The quantitative relationship between the in vitro susceptibility of herpes viruses to antivirals and the clinical response to therapy has not been established in humans, and virus sensitivity testing has not been standardized. Sensitivity testing results, expressed as the concentration of drug required to inhibit by 50% the growth of virus in cell culture (IC50), vary greatly depending upon a number of factors. Using plaque-reduction assays, the IC50 against herpes simplex virus isolates ranges from 0.02 to 13.5 mcg/mL for HSV-1 and from 0.01 to 9.9 mcg/mL for HSV-2. The IC50 for acyclovir against most laboratory strains and clinical isolates of VZV ranges from 0.12 to 10.8 mcg/mL. Acyclovir also demonstrates activity against the Oka vaccine strain of VZV with a mean IC50 of 1.35 mcg/mL.
Resistance of HSV and VZV to acyclovir can result from qualitative or quantitative changes in the viral TK and/or DNA polymerase. Clinical isolates of HSV and VZV with reduced susceptibility to acyclovir have been recovered from immunocompromised patients, especially with advanced HIV infection. While most of the acyclovir-resistant mutants isolated thus far from immunocompromised patients have been found to be TK-deficient mutants, other mutants involving the viral TK gene (TK partial and TK altered) and DNA polymerase have been isolated. TK-negative mutants may cause severe disease in infants and immunocompromised adults. The possibility of viral resistance to acyclovir should be considered in patients who show poor clinical response during therapy.
Acyclovir Injection - Clinical Pharmacology
The pharmacokinetics of acyclovir after intravenous administration have been evaluated in adult patients with normal renal function during Phase 1/2 studies after single doses ranging from 0.5 to 15 mg/kg and after multiple doses ranging from 2.5 to 15 mg/kg every 8 hours. Proportionality between dose and plasma levels is seen after single doses or at steady-state after multiple dosing. Average steady-state peak and trough concentrations from 1-hour infusions administered every 8 hours are given in Table 1.
|Dosage Regimen ||CSSmax ||CSStrough |
|5 mg/kg q 8 h |
|9.8 mcg/mL |
range: 5.5 to 13.8
|0.7 mcg/mL |
range: 0.2 to 1
|10 mg/kg q 8 h |
|22.9 mcg/mL |
range: 14.1 to 44.1
|1.9 mcg/mL |
range: 0.5 to 2.9
Concentrations achieved in the cerebrospinal fluid are approximately 50% of plasma values. Plasma protein binding is relatively low (9% to 33%) and drug interactions involving binding site displacement are not anticipated.
Renal excretion of unchanged drug is the major route of acyclovir elimination accounting for 62% to 91% of the dose. The only major urinary metabolite detected is 9-carboxymethoxymethylguanine accounting for up to 14.1% of the dose in patients with normal renal function.
The half-life and total body clearance of acyclovir are dependent on renal function as shown in Table 2.
|Creatinine Clearance (mL/min/1.73m2 ) ||Half-Life (hr) ||Total Body Clearance |
|(mL/min/1.73 m2) ||(mL/min/kg) |
|> 80 ||2.5 ||327 ||5.1 |
|50 to 80 ||3 ||248 ||3.9 |
|15 to 50 ||3.5 ||190 ||3.4 |
|0 (Anuric) ||19.5 ||29 ||0.5 |
Adults With Impaired Renal Function
Acyclovir for Injection, USP was administered at a dose of 2.5 mg/kg to 6 adult patients with severe renal failure. The peak and trough plasma levels during the 47 hours preceding hemodialysis were 8.5 mcg/mL and 0.7 mcg/mL, respectively.
Consult DOSAGE AND ADMINISTRATION section for recommended adjustments in dosing based upon creatinine clearance.
Acyclovir pharmacokinetics were determined in 16 pediatric patients with normal renal function ranging in age from 3 months to 16 years at doses of approximately 10 mg/kg and 20 mg/kg every 8 hours (Table 3). Concentrations achieved at these regimens are similar to those in adults receiving 5 mg/kg and 10 mg/kg every 8 hours, respectively (Table 1). Acyclovir pharmacokinetics were determined in 12 patients ranging in age from birth to 3 months at doses of 5 mg/kg, 10 mg/kg, and 15 mg/kg every 8 hours (Table 3).
|Parameter ||Birth to 3 Months of Age |
|3 Months to 12 Years of Age (n=16) |
|CL (mL/min/kg) ||4.46 + 1.61 ||8.44 + 2.92 |
|VDSS (L/kg) ||1.08 + 0.35 ||1.01 + 0.28 |
|Elimination half-life (hours) ||3.80 + 1.19 ||2.36 + 0.97 |
Acyclovir plasma concentrations are higher in geriatric patients compared to younger adults, in part due to age-related changes in renal function. Dosage reduction may be required in geriatric patients with underlying renal impairment (see PRECAUTIONS:Geriatric Use).
Coadministration of probenecid with acyclovir has been shown to increase the mean acyclovir half-life and the area under the concentration-time curve. Urinary excretion and renal clearance were correspondingly reduced.
Herpes Siplex Infections in Immuocompromised Patients
A multicenter trial of acyclovir at a dose of 250 mg/m2 every 8 hours (750 mg/m2/day) for 7 days was conducted in 98 immunocompromised patients (73 adults and 25 children) with orofacial, esophageal, genital and other localized infections (52 treated with acyclovir and 46 with placebo). Acyclovir decreased virus excretion, reduced pain, and promoted healing of lesions.
Initial Episodes of Herpes Genitalis
In placebo-controlled trials, 58 patients with initial genital herpes were treated with intravenous acyclovir 5 mg/kg or placebo (27 patients treated with acyclovir and 31 treated with placebo) every 8 hours for 5 days. Acyclovir decreased the duration of viral excretion, new lesion formation, and duration of vesicles, and promoted healing of lesions.
Herpes Simplex Encephalitis
Sixty-two patients ages 6 months to 79 years with brain biopsy-proven herpes simplex encephalitis were randomized to receive either acyclovir (10 mg/kg every 8 hours) or vidarabine (15 mg/kg/day) for 10 days (28 were treated with acyclovir and 34 with vidarabine).
Overall mortality at 12 months for patients treated with acyclovir was 25% compared to 59% for patients treated with vidarabine. The proportion of patients treated with acyclovir functioning normally or with only mild sequelae (e.g., decreased attention span) was 32% compared to 12% of patients treated with vidarabine.
Patients less than 30 years of age and those who had the least severe neurologic involvement at time of entry into study had the best outcome with treatment with acyclovir. An additional controlled study performed in Europe demonstrated similar findings.
Neonatal Herpes Simplex Virus Infection
Two hundred and two infants with neonatal herpes simplex infections were randomized to receive either acyclovir 10 mg/kg every 8 hours (n=107) or vidarabine 30 mg/kg/day (n=95) for 10 days. Outcomes are presented in Table 4.
* SEM refers to localized infection with disease limited to skin, eye, and/or mouth.
† CNS refers to infection of the central nervous system with compatible neurologic and CSF findings.
‡ DISS refers to visceral organ involvement such as hepatitis or pneumonitis with or without CNS involvement.
|HSV Disease Classification ||Treatment Group |
|Acyclovir (n=107) ||Vidarabine (n=95) |
|SEM* (n=85) ||0/54 ||0/31 |
|CNS† (n=71) ||5/35 ||5/36 |
|DISS‡ (n=46) ||11/18 ||14/28 |
Rates of neurologic sequelae at 1 year were comparable between the treatment groups.
Varicella-Zoster Infetions in Immunocompromised Patients
A multicenter trial of acyclovir at a dose of 500 mg/m2 every 8 hours for 7 days was conducted in immunocompromised patients with zoster infections (shingles). Ninety-four (94) patients were evaluated (52 patients were treated with acyclovir and 42 with placebo).
Acyclovir was superior to placebo as measured by reductions in cutaneous dissemination and visceral dissemination.
Indications and Usage for Acyclovir Injection
Herpes Simplex Infections in Immunocompromised Patients
Acyclovir for Injection, USP is indicated for the treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) in immunocompromised patients.
Initial Episodes of Herpes Genitalis
Acyclovir for Injection, USP is indicated for the treatment of severe initial clinical episodes of herpes genitalis in immuno-competent patients.
Herpes Simplex Encephalitis
Acyclovir for Injection, USP is indicated for the treatment of herpes simplex encephalitis.
Neonatal Herpes Simplex Virus Infection
Acyclovir for Injection, USP is indicated for the treatment of neonatal herpes infections.
Varicella-Zoster Infections in Immunocompromised Patients
Acyclovir for Injection, USP is indicated for the treatment of varicella-zoster (shingles) infections in immunocompromised patients.