Actavir 250/Actavir 500

Actavir 250/Actavir 500

aciclovir

Manufacturer:

Able Medical

Distributor:

Universal Medical Industry
Full Prescribing Info
Contents
Aciclovir sodium.
Description
Each vial contains Aciclovir Sodium eq. to aciclovir 250 mg or 500 mg, respectively.
Action
Pharmacology: Pharmacodynamics: Aciclovir is a synthetic purine nucleoside analogue with in vitro inhibitory activity against HSV-1, HSV-2, and varicella-zoster virus (VZV). In cell culture, aciclovir's highest antiviral activity is against HSV-1, followed in decreasing order of potency against HSV-2 and VZV.
The inhibitory activity of aciclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts aciclovir into aciclovir monophosphate, a nucleoside analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. In vitro, aciclovir triphosphate stops replication of herpes viral DNA. This is accomplished in three ways: Competitive inhibition of viral DNA polymerase, incorporation into and termination of the growing viral DNA chain, and inactivation of the viral DNA polymerase. The greater antiviral activity of aciclovir against HSV compared with VZV is due to its more efficient phosphorylation by the viral TK.
Pharmacokinetics: Absorption/Distribution: See Table 1.

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Concentrations achieved in the cerebrospinal fluid are approximately 50% of plasma values. Plasma protein binding is relatively low (9% to 33%).
Metabolism/Excretion: Renal excretion of unchanged drug is the major route of aciclovir 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 healthy renal function. (See Table 2.)

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Special populations: Renal function impairment: Aciclovir 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.
Elderly: Aciclovir plasma concentrations are higher in elderly patients compared with younger adults, in part due to age-related changes in renal function. Dosage reduction may be required in elderly patients with underlying renal impairment.
Indications/Uses
Systemic herpes simplex virus infections: Treatment of systemic herpes simplex virus infections.
Herpes simplex virus, mucocutaneous infection in immunocompromised patients: Treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) in immunocompromised patients.
Herpes simplex encephalitis: Treatment of herpes simplex encephalitis.
Herpes simplex virus, genital infection (severe): Treatment of severe initial clinical episodes of genital herpes in immunocompetent patients.
Herpes simplex virus, neonatal: Treatment of neonatal herpes infections.
Varicella-Zoster infections: Treatment of varicella (chickenpox) and herpes zoster (Shingles, Zoster).
Dosage/Direction for Use
Recommended Dose: Adult: For obese patients, administer the recommended adult dose using ideal body weight.
Systemic herpes simplex virus infections: Usual dosage: 5 mg/kg IV every 8 hours for 7-14 days.
Herpes simplex virus, mucocutaneous: Usual dosage: 5 mg/kg IV every 8 hours for 7 days.
HIV-infected patients: 5 mg/kg/dose IV every 8 hours, followed by oral aciclovir after lesions begin to heal; continue oral therapy until lesions are completely healed.
Herpes simplex encephalitis: 10 mg/kg IV every 8 hours for 10 days.
Herpes simplex virus, genital (severe initial episodes): Usual dosage: 5 mg/kg IV every 8 hours for 5 to 7 days.
Varicella-Zoster infections in immunocompromised patients: Usual dosage: 10 mg/kg IV every 8 hours for 7 days.
Pediatric: Systemic herpes simplex virus infections: Younger than 12 years: 10 mg/kg IV every 8 hours for 7-14 days.
Herpes simplex virus, mucocutaneous: 12 years and older: See Adult as previously mentioned.
Younger than 12 years: 10 mg/kg IV every 8 hours for 7 days.
Herpes simplex encephalitis: 12 years and older: 10 mg/kg IV every 8 hours for 10 days.
Herpes simplex virus, genital (severe initial episodes): 12 years and older: See Adult as previously mentioned.
Herpes simplex virus, neonatal: Birth to 3 months of age: In neonatal herpes simplex infection, doses of 20 mg/kg IV every 8 hours have been used; the safety and efficacy of these doses are not known.
Varicella-Zoster infections in immunocompromised patients: 12 years and older: See Adult as previously mentioned.
Younger than 12 years: Because of increased risk of nephrotoxicity associated with 20 mg/kg/dose, a 10 mg/kg/dose every 8 hours for 7 to 10 days or until no new lesions for 48 hours is recommended by several references.
Renal function impairment: See Table 3.

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Hemodialysis: The patient's dosing schedule should be adjusted so that an additional dose is administered after each dialysis.
Adults receiving continuous renal replacement therapy: One reference suggests a dosage of 5 to 10 mg/kg IV every 24 hours.
The following alternative recommendations assume ultrafiltration and dialysis flow rates of 1 to 2 L/h. A higher dosage is recommended when treating viral meningoencephalitis and varicella-zoster virus infections.
Continuous venovenous hemofiltration: 5 to 10 mg/kg IV every 24 hours.
Continuous venovenous hemodialysis or continuous venovenous hemodiafiltration: 5 to 10 mg/kg IV every 12 to 24 hours.
Adults receiving intermittent hemodialysis: 2.5 to 5 mg/kg IV every 24 hours administered after the dialysis session. This recommendation assumes the patient is receiving standard intermittent hemodialysis 3 times per week and completes the full dialysis sessions. Patients receiving extended daily dialysis may require increased doses. A higher dosage is recommended when treating viral meningoencephalitis and varicella-zoster virus infections.
Mode of Administration: Administer by constant infusion over 1 hour. Rapid or bolus IV injection must be avoided. Intramuscular (IM) or subcutaneous injection must also be avoided.
Preparation for administration: Reconstitution: The contents of the vial should be dissolved in sterile water for injection as follows: see Table 4.

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Solution for infusion in each case of Actavir 250 or Actavir 500 are prepared to give a concentration of aciclovir of 25 mg/mL. Shake the vial well to ensure complete dissolution before measuring and transferring each individual dose.
Dilution: This must then be further diluted to a final concentration not greater than about 5 mg/mL (0.5%) and given over 1 hour. Higher concentrations (eg, 10 mg/mL) may produce phlebitis or inflammation at the injection site upon inadvertent extravasation. Once diluted for administration, use each dose within 24 hours.
Admixture compatibilities: When reconstituting the contents of the vial, do not use bacteriostatic water for injection containing benzyl alcohol or parabens. Standard, commercially available electrolyte and glucose solutions are suitable for IV administration, including sodium chloride intravenous infusion (0.45% and 0.9% w/v), sodium chloride (0.18% w/v) and glucose (4% w/v) intravenous infusion, sodium chloride (0.45% w/v) and glucose (2.5% w/v) intravenous infusion, Ringer's lactate solution; biologic or colloidal fluids (eg, blood products, protein solutions) are not recommended.
Storage/Stability: The reconstituted solution should be used within 12 hours. Refrigeration of reconstituted solution may result in the formation of a precipitate that will redissolve at room temperature and diluted solution should be used within 24 hours of preparation.
Parenteral drug should be inspected visually for particle matter and discoloration prior to administration, whenever solution and container permit.
Overdosage
Overdosage of IV aciclovir has been reported following administration of rapid IV injection or inappropriately high doses and in patients with fluid and electrolyte imbalance, resulting in elevations in BUN and serum creatinine concentration and subsequent renal failure. At renal concentrations exceeding 2.5 mg/mL, aciclovir crystal may precipitate in the renal tubules, possibly causing renal dysfunction and eventual renal failure and anuria. A toxic dose has not been established for these agents. Aciclovir: Adult: Overdose ingestions up to 20 g have been reported, associated with the development of lethargy, agitation, seizures, and coma.
Pediatric: A 2-year-old received 800 mg aciclovir IV and developed transient neurotoxicity but recovered. Two neonates, who received 65 mg/kg and 100 mg/kg aciclovir IV had no evidence of toxicity. Transient nephrotoxicity developed in a neonate who received aciclovir 100 mg/kg IV three times daily for 4 days, and another who received 750 mg/kg IV.
Support: Management of mild to moderate toxicity: Patients generally do well with supportive care. Nausea and vomiting should be treated with antiemetics. Rashes should be treated with supportive care, discontinuation of the offending agent, and consideration of antihistamines and corticosteroids. With massive overdose, hydrate patients and monitor renal function.
Management of severe toxicity: Supportive care remains the mainstay of care in severe toxicity. Seizures should be treated with benzodiazepines as first line therapy, followed by barbiturates or propofol, if seizures persist. Hydrate patients and monitor urine output and renal function. Airway protection should be employed as need for patients with coma.
Decontamination: Hospital: Activated charcoal should be considered in patients with recent, large overdose if they are awake, alert, and willing to drink the charcoal. Gastric lavage has no role, as toxicity is not life threatening.
Antidote: None.
Monitoring of patient: Monitor renal function and urine output in patients receiving IV aciclovir with suspected toxicity or after massive oral overdose.
Enhanced elimination procedure: Aciclovir and famciclovir have low protein binding and volumes of distribution, and can be removed by hemodialysis. Hemodialysis has been used to reduce serum aciclovir concentrations in patients with toxicity, but is rarely indicated as patients do well with supportive care.
Patient disposition: Asymptomatic patients with inadvertent ingestion of these products may be observed at home. Patients with deliberate overdose and symptomatic patients should be sent to a healthcare facility for evaluation and treatment. Patients should be observed for 6 hours, primarily monitoring signs of co-ingestant toxicity or development of significant CNS depression. Follow-up renal function tests should be obtained in patients with massive overdose. Admit patients with severe toxicity characterized by CNS effects or renal injury.
Contraindications
Hypersensitivity to aciclovir, valaciclovir.
Special Precautions
Administration: Aciclovir for injection is intended for IV infusion only; do not administer topically, IM, orally, subcutaneously, or in the eye. IV infusions must be given over a period of at least 1 hour to reduce the risk of renal tubular damage.
Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, which has resulted in death, has occurred in immunocompromised patients receiving acyclovir therapy.
Renal effects: Precipitation of aciclovir crystals in renal tubules can occur if the maximum solubility of free aciclovir (2.5 mg/mL at 37°C [98.6°F] in water) is exceeded or if the drug is administered by bolus injection. Ensuring renal tubular damage can produce acute renal failure.
Abnormal renal function (decreased creatinine clearance) can occur as a result of aciclovir administration and depends on the state of the patient's hydration, other treatments, and the rate of drug administration.
Concomitant use of other nephrotoxic drugs, preexisting renal disease, and dehydration make further renal impairment with aciclovir more likely.
When dosage adjustments are required, they should be based on estimated creatinine clearance.
Hydration: Administration of aciclovir by IV infusion must be accompanied by adequate hydration.
Encephalopathic changes: Approximately 1% of patients receiving IV aciclovir have manifested encephalopathic changes characterized by either lethargy, obtundation, tremors, confusion, hallucinations, agitation, seizures, or coma. Use aciclovir with caution in those patients who have underlying neurologic abnormalities and those with serious renal, hepatic, or electrolyte abnormalities, or significant hypoxia.
Extravasation: Extravasation may occur during administration of aciclovir. If signs or symptoms of extravasation occur, stop the infusion immediately. If possible, withdraw 3 to 5 mL of blood to remove some of the drug. Hyaluronidase is an effective antidote for hyperosmolar drug infiltrations; administer promptly within few minutes to 1 hour after extravasation. Higher doses (150 units) have primarily been used in adults while lower doses (15 units) have been used in children.
Renal function impairment: The dose of acyclovir must be adjusted in patients with impaired renal function in order to avoid accumulation of acyclovir in the body.
In patients receiving acyclovir at higher doses, (eg, for herpes encephalitis), take specific care regarding renal function, particularly when patients are dehydrated or have any renal impairment.
Renal failure, in some cases resulting in death, has been observed with aciclovir therapy.
Use In Pregnancy & Lactation
Pregnancy: Category B. Teratogenic effects were not observed in animal reproduction studies. Aciclovir has been shown to cross the human placenta. Results from pregnancy registry, established in 1984 and closed in 1999, did not find an increase in the number or birth defects with exposure to acyclovir when compared with those expected in the general population. However, because of the small size of the registry and lack of long-term data, the manufacturer recommends using during pregnancy with caution and only when clearly needed. Aciclovir is recommended for the treatment of genital herpes in pregnant women.
Lactation: Aciclovir is excreted in breast milk. The manufacturer recommends that caution be exercised when administering aciclovir to breast-feeding women. Aciclovir may be used for the treatment of genital herpes in breast-feeding women. Breast-feeding mothers with herpetic lesions near or on the breast should avoid breast-feeding.
Adverse Reactions
The most frequent adverse reactions reported during administration of aciclovir were inflammation or phlebitis at the injection site in approximately 9% of the patients, and transient elevations of serum creatinine or blood urea nitrogen in 5% to 10% (the higher incidence occurred usually following rapid [less than 10 minutes] IV infusion). Nausea or vomiting occurred in approximately 7% of the patients (the majority occurring in non-hospitalized patients who received 10 mg/kg). Itching, rash, or hives occurred in approximately 2% of patients. Elevation of transaminases occurred in 1% to 2% of patients.
The following hematologic abnormalities occurred at a frequency of less than 1%: Anemia, neutropenia, thrombocytopenia, thrombocytosis, leukocytosis, and neutrophilia. In addition, anorexia and hematuria were observed.
Postmarketing: Cardiovascular: Hypotension.
CNS: Aggressive behavior, agitation, ataxia, coma, confusion, delirium, dizziness, dysarthria, encephalopathy, hallucinations, obtundation, paresthesia. Psychosis, seizure, somnolence, tremor. These symptoms may be marked, particularly in older adults.
Dermatologic:Alopecia, erythema multiforme, photosensitive rash, pruritus, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria. Severe local inflammatory reactions, including tissue necrosis, have occurred following infusion of aciclovir into extravascular tissues.
GI:Abdominal pain, diarrhea, GI distress, nausea.
GU: Renal failure, elevated blood urea nitrogen, elevated creatinine.
Hematologic/Lymphatic: Disseminated intravascular coagulation, hemolysis, leukocytoblastic vasculitis. Vasculitis, leukopenia, lymphadenopathy.
Hepatic: Elevated liver function tests, hepatitis, hyperbilirubinemia, jaundice.
Musculoskeletal: Myalgia.
Special Senses: Visual abnormalities.
Miscellaneous: Anaphylaxis, angioedema, fatigue, fever, headache, pain, peripheral edema.
Drug Interactions
Metabolism/Transport effects: None known. (See Table 5.)

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Storage
Store below 30°C.
MIMS Class
ATC Classification
J05AB01 - aciclovir ; Belongs to the class of nucleosides and nucleotides excluding reverse transcriptase inhibitors. Used in the systemic treatment of viral infections.
Presentation/Packing
Actavir 250 powd for inj (vial, white, sterile) 250 mg x 1 x 1's. Actavir 500 powd for inj (vial, white, sterile) 500 mg x 1 x 1's.
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