Zoylex

Zoylex

aciclovir

Manufacturer:

Korea United Pharm

Distributor:

S Charoen Bhaesaj Trading
Full Prescribing Info
Contents
Aciclovir.
Description
Each vial (10 ml) contains Aciclovir 250 mg.
Action
Pharmacology: Pharmacodynamics: Aciclovir, a synthetic acyclic purine nucleoside analog, is a substrate with a high degree of specificity for herpes simplex and varicella-zoster-specified thymidine kinase. Aciclovir is a poor substrate for host cell-specified thymidine kinase. Herpes simplex and varicella-zoster-specified thymidine kinase transform aciclovir to aciclovir monophosphate which is then transformed by number of cellular enzymes to aciclovir diphosphate and aciclovir triphosphate. Aciclovir triphosphate is both an inhibitor of, and a substrate for, herpes virus-specified DNA polymerase. Although the cellular α-DNA polymerase in infected cells may also be inhibited by aciclovir triphosphate, this occurs only at concentrations of aciclovir triphosphate which are higher than those which inhibit the herpes virus-specified DNA polymerase. Aciclovir is selectively converted to its active form in herpes virus-infected cells and is thus preferentially taken up by these cells. Aciclovir has demonstrated a very much lower toxic potential in vitro for normal uninfected cells because: less is taken up; less is converted to the active form; cellular α-DNA polymerase has a lower sensitivity to the action of the active form of the drug. A combination of the thymidine kinase specificity, inhibition of DNA polymerase and premature termination of DNA synthesis results in inhibition of herpes virus replication. No effect on latent non-replicating virus has been demonstrated. Inhibition of the virus reduces the period of viral shedding, limits the degree of spread and level of pathology, and thereby facilitates healing. During suppression, there is no evidence that aciclovir prevents neural migration of the virus. It aborts episodes of recurrent herpes due to inhibition of viral replication following reactivation.
Pharmacokinetics: Absorption: In adults with normal renal function receiving single aciclovir doses ranging from 0.5 to 15 mg/kg or multiple doses ranging from 2.5 to 15 mg/kg every 8 hours indicate that plasma concentrations of the drug are dose proportional.
Distribution: Aciclovir is widely distributed into body tissues and fluids including the brain, kidney, saliva, lung, liver, muscle, spleen, uterus, vaginal mucosa and secretions, CSF, and herpetic vesicular fluid. CSF aciclovir concentration is 50% of plasma concentrations.
The apparent volume of distribution of aciclovir is reported to be 32.4-61.8 L/1.73 m2 in adults and 28.8, 31.6, 42.0, or 51.2-53.6 L/1.73 m2 in neonates up to 3 months of age, children 1-2 years, 2-7 years, or 7-12 years of age, respectively. Aciclovir is approximately 9-33% bound to plasma proteins.
Metabolism: Converted by viral enzymes to aciclovir monophosphate, and further converted to diphosphate then triphosphate (active form) by cellular enzymes.
Excretion: Renal excretion of unchanged drug by glomerular filtration and tubular secretion is the major route of aciclovir elimination, accounting for 62 to 91% of the dose administered.
The half-life elimination (terminal phase) of aciclovir is reported to be 3.8 ± 1.19 hours in neonate and infants ≤3 months, 2.36 ± 0.97 hours in infants >3 months to children ≤12 years, ~2.5 hours in adults with normal renal function, 20 hours in adults with ESRD, and ~5 hours in patients with hemodialysis.
The pharmacokinetics of aciclovir in children generally are similar to that reported in adults.
Aciclovir plasma concentrations are higher in geriatric patients than in younger adults, in part due to age-related changes in renal function.
Indications/Uses
Treatment of herpes simplex virus infections.
Treatment of varicella zoster virus infections.
Treatment of neonatal herpes simplex virus infections.
Dosage/Direction for Use
Recommended Dose: Aciclovir should be given by slow IV infusion at a constant rate over at least 1 hour. (See Table 1.)

Click on icon to see table/diagram/image

Dosage in patients with impaired renal function. The following adjustments in dosage are suggested. (See Table 2.)

Click on icon to see table/diagram/image

Use in geriatric: This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Mode of Administration: Aciclovir should be given by slow IV infusion at a constant rate over at least 1 hour.
Aciclovir may given by infusion using a controlled-rate infusion pump.
Aciclovir should not be diluted to a concentration greater than 5 mg/ml (0.5%w/v) for administration by infusion.
When diluted in accordance with the recommended schedules, aciclovir is known to be compatible with the following infusion fluids and stable for up to 12 hours at temperature between 15 to 25°C: 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; Compound sodium lactate intravenous infusion (Hartmann's solution).
After addition of aciclovir to an infusion solution the mixture should be shaken to ensure thorough mixing.
Since no antimicrobial preservative is included, dilution must be carried out under full aseptic condition, immediately before use, and any unused solution discard.
When visible turbidity or crystallization appears in the solution before or during the infusion, the preparation should be discarded. The diluted solutions should not be refrigerated.
ZOYLEX is alkaline solution. It is incompatible with other drug according to change of pH. Therefore, combination of aciclovir and other drug should be avoided.
Overdosage
Aciclovir overdosage involving ingestion of up to 20 g of the drug have been reported. Overdosage of IV aciclovir has been reported following administration of rapid IV injections 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. Other adverse effects reported with aciclovir overdosage include agitation, coma, lethargy, and seizures. If acute renal failure and anuria occur, use of hemodialysis should be considered until renal function is restored.
Contraindications
Patients who have known to be previously hypersensitive to aciclovir or valaciclovir.
Special Precautions
Care should be observed when administering aciclovir injection to patients with renal abnormal function, patients with hepatic dysfunction, children patient, and elderly patients.
Aciclovir should be used with caution in patients receiving other nephrotoxic drugs concurrently since the risk of aciclovir-induced renal impairment.
Adequate hydration should be maintained in patients receiving aciclovir.
Acivlovir should be given only by slow IV infusion over a period of at least 1 hour to reduce the risk of aciclovir-induced renal impairment.
Parenteral aciclovir therapy can cause signs and symptoms of encephalopathy. Aciclovir should be used with caution in patient with underlying neurologic abnormalities and in patients with serious renal, hepatic, or electrolyte abnormalities or substantial hypoxia.
Use In Pregnancy & Lactation
Pregnancy: There are no adequate and controlled studies to date using aciclovir in pregnant woman. Aciclovir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Lactation: Limited data indicate that aciclovir is distributed into milk. Aciclovir should be administered to nursing women with caution and only when indicated.
Adverse Reactions
Local effects: Severe local inflammatory reactions, including tissue necrosis, have occurred following infusion of aciclovir into extravascular tissues.
Renal effects: Elevation of BUN and serum creatinine level, anuria, red blood cell in urine precipitation have been reported occasionally. Renal impairment developing during treatment with aciclovir have been reported most frequently when the drug was administered by rapid (over less than 10 minutes) IV infusion rather than over the recommended period for IV infusion (at least 1 hour).
Psychoneurotic effects: Reversible neurological reactions such as confusion, hallucinations, agitation, tremors, somnolence, psychosis, paresthesia, dizziness, headache, fatigue, convulsions and coma have been associated with I.V. therapy, usually in medically complicated cases.
GI effects: Usually diarrhea, vomiting, nausea, and abdominal pain have been reported in patients receiving aciclovir.
Hematologic: Usually occurred anemia, thrombocytopenia, lymphadenopathy, leukopenia, disseminated intravascular coagulation, hemolysis, leukocytoclastic vasculitis.
Skin: Alopecia, erythema multiforme, photosensitive rash, pruritus, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria.
Other Adverse Effects: Fever and pain have been reported in patients receiving aciclovir. Elevated liver function test results, hepatitis, hyperbilirubinemia, jaundice, hypotension, myalgia, peripheral edema, thirst, and visual abnormalities have been reported rarely in patients receiving aciclovir
Drug Interactions
Aciclovir is a weak CYP1A2 inhibitors. When aciclovir is administered concomitantly with theophylline, toxicosis of theophylline could occur.
The level of aciclovir may be increased by foscarnet, mycophenolate, and tenofovir.
Aciclovir may increase the level of clozapine, mycophenolate, tenofovir, tizanidine, and zidovudine.
Coadministration of zidovudine with aciclovir has been shown the neurotoxicity. Coadministration of probenecid with aciclovir has been shown to increase the mean aciclovir half-life and the area under the concentration-time curve. Urinary excretion and renal clearance were correspondingly reduced.
IV aciclovir should be used with caution in patients receiving interferon. The drugs have an additive or synergistic antiviral effect.
Storage
Preserve in hermetic containers.
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
Conc for soln for infusion (vial) 250 mg/10 mL (clear, colorless) x 10's.
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