ZOVIRAX Acyclovir 250mg Powder for IV Injection 1's
RXDRUG-DR-XY1599-1pc
Discreet Packaging
FDA-registered Products
FDA-licensed Pharmacies
Indications/Uses
Tablet: Acyclovir (Zovirax) oral formulations are indicated for the treatment of herpes simplex virus infections of the skin and mucous membranes including initial and recurrent genital herpes.
Acyclovir (Zovirax) oral formulations are indicated for the suppression (prevention of recurrences) of recurrent herpes simplex infections in immune-competent patients. Acyclovir (Zovirax) oral formulations are indicated for the prophylaxis of herpes simplex infections in immune-compromised patients.
Acyclovir (Zovirax) oral formulations are indicated for the treatment of varicella infections (chicken-pox) and herpes zoster (shingles).
Studies have shown that early treatment of shingles with Acyclovir (Zovirax) has a beneficial effect on pain and can reduce the incidence of post-herpetic neuralgia (zoster-associated pain).
Acyclovir (Zovirax) oral formulations are indicated for the management of certain severely immunocompromised patients, namely those with advanced HIV disease (CD4+ counts <200/mm3, including patients with AIDS or severe ARC) or following bone marrow transplantation.
Studies have shown that oral Acyclovir (Zovirax) given in conjunction with antiretroviral therapy (mainly oral RETROVIR) reduced mortality in patients with advanced HIV disease and that oral Acyclovir (Zovirax) preceded by one month's treatment with intravenous Acyclovir (Zovirax) reduced mortality in bone marrow transplant recipients. In addition, oral Acyclovir (Zovirax) provided effective prophylaxis for herpes virus disease.
Injection: Acyclovir (Zovirax) IV for infusion is indicated for the treatment of herpes simplex infections, prophylaxis of herpes simplex infections in immune-compromised patients, treatment of varicella zoster infections, herpes simplex infections in the neonate.
Acyclovir (Zovirax) oral formulations are indicated for the suppression (prevention of recurrences) of recurrent herpes simplex infections in immune-competent patients. Acyclovir (Zovirax) oral formulations are indicated for the prophylaxis of herpes simplex infections in immune-compromised patients.
Acyclovir (Zovirax) oral formulations are indicated for the treatment of varicella infections (chicken-pox) and herpes zoster (shingles).
Studies have shown that early treatment of shingles with Acyclovir (Zovirax) has a beneficial effect on pain and can reduce the incidence of post-herpetic neuralgia (zoster-associated pain).
Acyclovir (Zovirax) oral formulations are indicated for the management of certain severely immunocompromised patients, namely those with advanced HIV disease (CD4+ counts <200/mm3, including patients with AIDS or severe ARC) or following bone marrow transplantation.
Studies have shown that oral Acyclovir (Zovirax) given in conjunction with antiretroviral therapy (mainly oral RETROVIR) reduced mortality in patients with advanced HIV disease and that oral Acyclovir (Zovirax) preceded by one month's treatment with intravenous Acyclovir (Zovirax) reduced mortality in bone marrow transplant recipients. In addition, oral Acyclovir (Zovirax) provided effective prophylaxis for herpes virus disease.
Injection: Acyclovir (Zovirax) IV for infusion is indicated for the treatment of herpes simplex infections, prophylaxis of herpes simplex infections in immune-compromised patients, treatment of varicella zoster infections, herpes simplex infections in the neonate.
Dosage/Direction for Use
Tablet: Adults: Treatment of Herpes Simplex: For treatment of herpes simplex infections, 200 mg Acyclovir (Zovirax) should be taken five times daily at approximately four-hourly intervals omitting the night time dose. Treatment should continue for five days but in severe initial infections may have to be extended.
In severely immune-compromised patients (e.g. after marrow transplant) or in patients with impaired absorption from the gut the dose can be doubled to 400 mg or, alternatively, intravenous dosing could be considered.
Dosing should begin as early as possible after the start of an infection; for recurrent episodes this should preferably be during the prodromal period or when lesions first appear.
Suppression of Herpes Simplex: For suppression of herpes simplex infections in immune-competent patients, 200 mg Acyclovir (Zovirax) should be taken four times daily at approximately six-hourly intervals.
Many patients may be conveniently managed on a regimen of 400 mg Acyclovir (Zovirax) taken twice daily at approximately twelve-hourly intervals.
Dosage titration down to 200 mg Acyclovir (Zovirax) taken thrice daily at approximately eight-hourly intervals or even twice daily at approximately twelve-hourly intervals, may prove effective.
Some patients may experience break-through infections on total daily doses of 800 mg Acyclovir (Zovirax).
Therapy should be interrupted periodically at intervals of six to twelve months in order to observe possible changes in the natural history of the disease.
Prophylaxis of Herpes Simplex: For prophylaxis of herpes simplex infections in immune-compromised patients, 200 mg Acyclovir (Zovirax) should be taken four times daily at approximately six-hourly intervals.
In severely immune-compromised patients (e.g. after marrow transplant) or in patients with impaired absorption from the gut the dose can be doubled to 400 mg or, alternatively, intravenous dosing could be considered.
The duration of prophylactic administration is determined by the duration of the period at risk.
Treatment of Varicella and Herpes Zoster: For treatment of varicella and herpes zoster infections, 800 mg Acyclovir (Zovirax) should be taken five times daily at approximately four-hourly intervals, omitting the night time dose. Treatment should continue for seven days.
In severely immune-compromised patients (e.g. after marrow transplant) or in patients with impaired absorption from the gut, consideration should be given to intravenous dosing.
Dosing should begin as early as possible after the start of an infection. Treatment yields better results if initiated as soon as possible after onset of the rash.
Management of Severely Immunocompromised Patients: For management of severely immunocompromised patients, 800 mg Acyclovir (Zovirax) should be taken four times daily at approximately six-hourly intervals.
In the management of bone marrow recipients this would normally be preceded by up to one month's therapy with intravenous Acyclovir (Zovirax) [see Acyclovir (Zovirax) IV for infusion prescribing information].
The duration of treatment studied in bone marrow transplant patients was 6 months (from 1 to 7 months post-transplant). In patients with advanced HIV disease, study treatment was 12 months, but it is likely that these patients would continue to benefit from a longer duration of treatment.
Infants and Children: For treatment of herpes simplex infections, and for prophylaxis of herpes simplex infections in the immune-compromised, children aged two years and over should be given adult dosages and infants and children below the age of two years should be given half the adult dose.
For treatment of varicella infections in children: 6 years and over: 800 mg Acyclovir (Zovirax) four times daily; 2-<6 years: 400 mg Acyclovir (Zovirax) four times daily; Under 2 years: 200 mg Acyclovir (Zovirax) four times daily. Dosing may be more accurately calculated as 20 mg Acyclovir (Zovirax)/kg bodyweight (not to exceed 800 mg) four times daily. Treatment should continue for five days.
No specific data are available on the suppression of herpes simplex infections or the treatment of herpes zoster infections in immune-competent children.
Limited data suggest that for management of severely immunocompromised children, over two years of age, the adult dose may be given.
Elderly: The possibility of renal impairment in the elderly must be considered and the dosage should be adjusted accordingly (see Renal Impairment as follows).
Adequate hydration of elderly patients taking high oral doses of Acyclovir (Zovirax) should be maintained.
Renal Impairment: Caution is advised when administering Acyclovir (Zovirax) oral formulations to patients with impaired renal function. Adequate hydration should be maintained.
In the treatment and prophylaxis of herpes simplex infections in patients with impaired renal function, the recommended oral doses will not lead to accumulation of acyclovir above levels that have been established safe by intravenous infusion. However, for patients with severe renal impairment (creatinine clearance less than 10 ml/minute) an adjustment of dosage to 200 mg twice daily at approximately twelve-hourly intervals is recommended.
In the treatment of varicella and herpes zoster infections, and in the management of severely immunocompromised patients it is recommended to adjust the dosage to 800 mg twice daily, at approximately twelve-hourly intervals, for patients with severe renal impairment (creatinine clearance less than 10 mL/minute) and to 800 mg three times daily, at intervals of approximately eight hours, for patients with moderate renal impairment (creatinine clearance in the range 10 to 25 mL/minute).
Injection: To be gives as intravenous infusion over 1 hour.
A course of treatment with Acyclovir (Zovirax) IV for infusion usually lasts 5 days, but this may be adjusted according to the patient's condition and response to therapy. Treatment for herpes encephalitis usually lasts 10 days.
Treatment for neonatal herpes usually lasts 14-21 days.
The duration of prophylactic administration of Acyclovir (Zovirax) IV for infusion is determined by the duration of the period at risk.
Adults: Treatment of Herpes Simplex: Obese patients should be dosed at the recommended adult dose using ideal body weight, rather than actual body weight.
Patients with herpes simplex (except herpes encephalitis) should be given acyclovir IV for infusion in doses of 5 mg/kg bodyweight every eight hours if renal function is not impaired.
Patients with herpes encephalitis should be given acyclovir IV for infusion in doses of 10 mg/kg bodyweight every eight hours provided renal function is not impaired.
Prophylaxis of Herpes Simplex in Immune-compromised Patients: Obese patients should be dosed at the recommended adult dose using ideal body weight, rather than actual body weight.
Refer to adult dosing recommendations for the treatment of herpes simplex with Acyclovir (Zovirax) IV for infusion.
Treatment of Varicella and Herpes Zoster: Obese patients should be dosed at the recommended adult dose using ideal body weight, rather than actual body weight.
Patients with varicella zoster infections should be given acyclovir IV for infusion in doses of 5 mg/kg bodyweight every eight hours if renal function is not impaired.
Immune-compromised patients with varicella zoster infections should be given acyclovir IV for infusion in doses of 10 mg/kg bodyweight every eight hours provided renal function is not impaired.
Infants and Children: The dose of Acyclovir (Zovirax) IV for infusion for infants and children aged between 3 months and 12 years is calculated on the basis of body surface area. Infants and children 3 months of age or older with herpes simplex (except herpes encephalitis) or varicella zoster infections should be given Acyclovir (Zovirax) IV for infusion in doses of 250 mg per square metre body surface area every 8 hours if renal is not impaired.
In immune-compromised infants and children with varicella zoster infections or herpes encephalitis, Acyclovir (Zovirax) IV for infusion should be given in doses of 500 mg per square metre body surface area every 8 hours if renal function is not impaired.
Infants and children with impaired renal function require an appropriately modified dose, according to the degree of impairment.
Neonates: The dosage of Acyclovir (Zovirax) IV for infusion in neonates is calculated on the basis of bodyweight.
The recommended regimen for treatment for known or suspected neonatal herpes is Acyclovir (Zovirax) IV 20 mg/kg body weight IV every 8 hours for 21 days for disseminated and CNS disease, or for 14 days for disease limited to the skin and mucous membranes. Patients with impaired renal function require an appropriately modified dose, according to the degree of impairment (see Renal Impairment).
Elderly: The possibility of renal impairment in the elderly must be considered and the dosage should be adjusted accordingly (see Renal Impairment).
Adequate hydration should be maintained.
Renal Impairment: Caution is advised when administering Acyclovir (Zovirax) IV for infusion to patients with impaired renal function. Adequate hydration should be maintained.
Dosage adjustment for patients with renal impairment is based on creatinine clearance, in units of mL/min for adults and adolescents and in units of mL/min/1.73 m2 for infants and children less than 13 years of age. The following adjustments in dosage are suggested: See Tables 1 and 2.
In severely immune-compromised patients (e.g. after marrow transplant) or in patients with impaired absorption from the gut the dose can be doubled to 400 mg or, alternatively, intravenous dosing could be considered.
Dosing should begin as early as possible after the start of an infection; for recurrent episodes this should preferably be during the prodromal period or when lesions first appear.
Suppression of Herpes Simplex: For suppression of herpes simplex infections in immune-competent patients, 200 mg Acyclovir (Zovirax) should be taken four times daily at approximately six-hourly intervals.
Many patients may be conveniently managed on a regimen of 400 mg Acyclovir (Zovirax) taken twice daily at approximately twelve-hourly intervals.
Dosage titration down to 200 mg Acyclovir (Zovirax) taken thrice daily at approximately eight-hourly intervals or even twice daily at approximately twelve-hourly intervals, may prove effective.
Some patients may experience break-through infections on total daily doses of 800 mg Acyclovir (Zovirax).
Therapy should be interrupted periodically at intervals of six to twelve months in order to observe possible changes in the natural history of the disease.
Prophylaxis of Herpes Simplex: For prophylaxis of herpes simplex infections in immune-compromised patients, 200 mg Acyclovir (Zovirax) should be taken four times daily at approximately six-hourly intervals.
In severely immune-compromised patients (e.g. after marrow transplant) or in patients with impaired absorption from the gut the dose can be doubled to 400 mg or, alternatively, intravenous dosing could be considered.
The duration of prophylactic administration is determined by the duration of the period at risk.
Treatment of Varicella and Herpes Zoster: For treatment of varicella and herpes zoster infections, 800 mg Acyclovir (Zovirax) should be taken five times daily at approximately four-hourly intervals, omitting the night time dose. Treatment should continue for seven days.
In severely immune-compromised patients (e.g. after marrow transplant) or in patients with impaired absorption from the gut, consideration should be given to intravenous dosing.
Dosing should begin as early as possible after the start of an infection. Treatment yields better results if initiated as soon as possible after onset of the rash.
Management of Severely Immunocompromised Patients: For management of severely immunocompromised patients, 800 mg Acyclovir (Zovirax) should be taken four times daily at approximately six-hourly intervals.
In the management of bone marrow recipients this would normally be preceded by up to one month's therapy with intravenous Acyclovir (Zovirax) [see Acyclovir (Zovirax) IV for infusion prescribing information].
The duration of treatment studied in bone marrow transplant patients was 6 months (from 1 to 7 months post-transplant). In patients with advanced HIV disease, study treatment was 12 months, but it is likely that these patients would continue to benefit from a longer duration of treatment.
Infants and Children: For treatment of herpes simplex infections, and for prophylaxis of herpes simplex infections in the immune-compromised, children aged two years and over should be given adult dosages and infants and children below the age of two years should be given half the adult dose.
For treatment of varicella infections in children: 6 years and over: 800 mg Acyclovir (Zovirax) four times daily; 2-<6 years: 400 mg Acyclovir (Zovirax) four times daily; Under 2 years: 200 mg Acyclovir (Zovirax) four times daily. Dosing may be more accurately calculated as 20 mg Acyclovir (Zovirax)/kg bodyweight (not to exceed 800 mg) four times daily. Treatment should continue for five days.
No specific data are available on the suppression of herpes simplex infections or the treatment of herpes zoster infections in immune-competent children.
Limited data suggest that for management of severely immunocompromised children, over two years of age, the adult dose may be given.
Elderly: The possibility of renal impairment in the elderly must be considered and the dosage should be adjusted accordingly (see Renal Impairment as follows).
Adequate hydration of elderly patients taking high oral doses of Acyclovir (Zovirax) should be maintained.
Renal Impairment: Caution is advised when administering Acyclovir (Zovirax) oral formulations to patients with impaired renal function. Adequate hydration should be maintained.
In the treatment and prophylaxis of herpes simplex infections in patients with impaired renal function, the recommended oral doses will not lead to accumulation of acyclovir above levels that have been established safe by intravenous infusion. However, for patients with severe renal impairment (creatinine clearance less than 10 ml/minute) an adjustment of dosage to 200 mg twice daily at approximately twelve-hourly intervals is recommended.
In the treatment of varicella and herpes zoster infections, and in the management of severely immunocompromised patients it is recommended to adjust the dosage to 800 mg twice daily, at approximately twelve-hourly intervals, for patients with severe renal impairment (creatinine clearance less than 10 mL/minute) and to 800 mg three times daily, at intervals of approximately eight hours, for patients with moderate renal impairment (creatinine clearance in the range 10 to 25 mL/minute).
Injection: To be gives as intravenous infusion over 1 hour.
A course of treatment with Acyclovir (Zovirax) IV for infusion usually lasts 5 days, but this may be adjusted according to the patient's condition and response to therapy. Treatment for herpes encephalitis usually lasts 10 days.
Treatment for neonatal herpes usually lasts 14-21 days.
The duration of prophylactic administration of Acyclovir (Zovirax) IV for infusion is determined by the duration of the period at risk.
Adults: Treatment of Herpes Simplex: Obese patients should be dosed at the recommended adult dose using ideal body weight, rather than actual body weight.
Patients with herpes simplex (except herpes encephalitis) should be given acyclovir IV for infusion in doses of 5 mg/kg bodyweight every eight hours if renal function is not impaired.
Patients with herpes encephalitis should be given acyclovir IV for infusion in doses of 10 mg/kg bodyweight every eight hours provided renal function is not impaired.
Prophylaxis of Herpes Simplex in Immune-compromised Patients: Obese patients should be dosed at the recommended adult dose using ideal body weight, rather than actual body weight.
Refer to adult dosing recommendations for the treatment of herpes simplex with Acyclovir (Zovirax) IV for infusion.
Treatment of Varicella and Herpes Zoster: Obese patients should be dosed at the recommended adult dose using ideal body weight, rather than actual body weight.
Patients with varicella zoster infections should be given acyclovir IV for infusion in doses of 5 mg/kg bodyweight every eight hours if renal function is not impaired.
Immune-compromised patients with varicella zoster infections should be given acyclovir IV for infusion in doses of 10 mg/kg bodyweight every eight hours provided renal function is not impaired.
Infants and Children: The dose of Acyclovir (Zovirax) IV for infusion for infants and children aged between 3 months and 12 years is calculated on the basis of body surface area. Infants and children 3 months of age or older with herpes simplex (except herpes encephalitis) or varicella zoster infections should be given Acyclovir (Zovirax) IV for infusion in doses of 250 mg per square metre body surface area every 8 hours if renal is not impaired.
In immune-compromised infants and children with varicella zoster infections or herpes encephalitis, Acyclovir (Zovirax) IV for infusion should be given in doses of 500 mg per square metre body surface area every 8 hours if renal function is not impaired.
Infants and children with impaired renal function require an appropriately modified dose, according to the degree of impairment.
Neonates: The dosage of Acyclovir (Zovirax) IV for infusion in neonates is calculated on the basis of bodyweight.
The recommended regimen for treatment for known or suspected neonatal herpes is Acyclovir (Zovirax) IV 20 mg/kg body weight IV every 8 hours for 21 days for disseminated and CNS disease, or for 14 days for disease limited to the skin and mucous membranes. Patients with impaired renal function require an appropriately modified dose, according to the degree of impairment (see Renal Impairment).
Elderly: The possibility of renal impairment in the elderly must be considered and the dosage should be adjusted accordingly (see Renal Impairment).
Adequate hydration should be maintained.
Renal Impairment: Caution is advised when administering Acyclovir (Zovirax) IV for infusion to patients with impaired renal function. Adequate hydration should be maintained.
Dosage adjustment for patients with renal impairment is based on creatinine clearance, in units of mL/min for adults and adolescents and in units of mL/min/1.73 m2 for infants and children less than 13 years of age. The following adjustments in dosage are suggested: See Tables 1 and 2.
Overdosage
Symptoms & Signs: Overdosage of IV acyclovir has resulted in elevations of serum creatinine, blood urea nitrogen and subsequent renal failure. Neurological effects including confusion, hallucinations, agitation, seizures and coma have been described in association with IV overdosage.
Tablet: Acyclovir is only partly absorbed in the gastrointestinal tract. Patients have ingested overdoses of up to acyclovir 20 g on a single occasion, usually without toxic effects. Accidental repeated overdoses of oral acyclovir over several days have been associated with GI effects (eg, nausea and vomiting) and neurological effects (headache and confusion).
Treatment: Patients should be observed closely for signs of toxicity. Hemodialysis significantly enhances the removal of acyclovir from the blood and may therefore, be considered a management option in the event of symptomatic overdose.
Tablet: Acyclovir is only partly absorbed in the gastrointestinal tract. Patients have ingested overdoses of up to acyclovir 20 g on a single occasion, usually without toxic effects. Accidental repeated overdoses of oral acyclovir over several days have been associated with GI effects (eg, nausea and vomiting) and neurological effects (headache and confusion).
Treatment: Patients should be observed closely for signs of toxicity. Hemodialysis significantly enhances the removal of acyclovir from the blood and may therefore, be considered a management option in the event of symptomatic overdose.
Administration
May be taken with or without food: May be taken w/ meals to reduce GI discomfort.
Contraindications
Hypersensitivity to acyclovir or valacyclovir.
Special Precautions
Infusion: In patients receiving Zovirax IV for infusion at higher doses (eg, for herpes encephalitis), specific care regarding renal function should be taken, particularly when patients are dehydrated or have any renal impairment. Reconstituted Acyclovir Zovirax IV for infusion has a pH of approximately 11 and should not be administered by mouth.
Hydration Status: Tablet: Care should be taken to maintain adequate hydration in patients receiving high oral doses of acyclovir.
Renal Impairment: Tablet: Acyclovir is eliminated by renal clearance; therefore the dose must be reduced in patients with renal impairment (see Dosage & Administration).
Effects on the Ability to Drive or Operate Machinery: Tablet: The clinical status of the patient and the adverse event profile of Zovirax should be borne in mind when considering the patient's ability to drive or operate machinery. There have been no studies to investigate the effect of acyclovir on driving performance or the ability to operate machinery. Further, a detrimental effect on such activities cannot be predicted from the pharmacology of the active substance.
Infusion: Zovirax IV for infusion is generally used in an in-patient hospital population and information on ability to drive and operate machinery is not usually relevant. There have been no studies to investigate the effect of acyclovir on driving performance or the ability to operate machinery.
Use in Elderly: Elderly patients are likely to have reduced renal function and therefore, the need for dose reduction must be considered in this group of patients. Both elderly patients and patients with renal impairment are at increased risk of developing neurological side effects and should be closely monitored for evidence of these effects. In the reported cases, these reactions were generally reversible on discontinuation of treatment (see Adverse Reactions).
Hydration Status: Tablet: Care should be taken to maintain adequate hydration in patients receiving high oral doses of acyclovir.
Renal Impairment: Tablet: Acyclovir is eliminated by renal clearance; therefore the dose must be reduced in patients with renal impairment (see Dosage & Administration).
Effects on the Ability to Drive or Operate Machinery: Tablet: The clinical status of the patient and the adverse event profile of Zovirax should be borne in mind when considering the patient's ability to drive or operate machinery. There have been no studies to investigate the effect of acyclovir on driving performance or the ability to operate machinery. Further, a detrimental effect on such activities cannot be predicted from the pharmacology of the active substance.
Infusion: Zovirax IV for infusion is generally used in an in-patient hospital population and information on ability to drive and operate machinery is not usually relevant. There have been no studies to investigate the effect of acyclovir on driving performance or the ability to operate machinery.
Use in Elderly: Elderly patients are likely to have reduced renal function and therefore, the need for dose reduction must be considered in this group of patients. Both elderly patients and patients with renal impairment are at increased risk of developing neurological side effects and should be closely monitored for evidence of these effects. In the reported cases, these reactions were generally reversible on discontinuation of treatment (see Adverse Reactions).
Use In Pregnancy & Lactation
Use in Pregnancy: A post-marketing acyclovir pregnancy registry has documented pregnancy outcomes in women exposed to any formulation of acyclovir. The registry findings have not shown an increase in the number of birth defects amongst Zovirax exposed subjects compared with the general population, and any birth defects showed no uniqueness or consistent pattern to suggest a common cause. The use of acyclovir should be considered only when the potential benefits outweigh the possibility of unknown risks.
Use in Lactation: Following oral administration of acyclovir 200 mg 5 times a day, acyclovir has been detected in breast milk at concentrations ranging from 0.6-4.1 times the corresponding plasma levels. These levels would potentially expose nursing infants to acyclovir dosages of up to 0.3 mg/kg/day. Caution is therefore advised if acyclovir is to be administered to a nursing woman.
Use in Lactation: Following oral administration of acyclovir 200 mg 5 times a day, acyclovir has been detected in breast milk at concentrations ranging from 0.6-4.1 times the corresponding plasma levels. These levels would potentially expose nursing infants to acyclovir dosages of up to 0.3 mg/kg/day. Caution is therefore advised if acyclovir is to be administered to a nursing woman.
Adverse Reactions
The frequency categories associated with the adverse events as follows are estimates. For most events, suitable data for estimating incidence were not available. In addition, adverse events may vary in their incidence depending on the indication.
The following convention has been used for the classification of adverse effects in terms of frequency: Very common ≥1/10, common ≥1/100 and <1/10, uncommon ≥1/1,000 and <1/100, rare ≥1/10,000 and <1/1,000, very rare <1/10,000.
Tablet: Blood and Lymphatic System Disorders: Very Rare: Anemia, leukopenia, thrombocytopenia.
Immune System Disorders: Rare: Anaphylaxis.
Psychiatric and Nervous System Disorders: Common: Headache, dizziness. Very Rare: Agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsions, somnolence, encephalopathy and coma.
The previously mentioned events are generally reversible and usually reported in patients with renal impairment or with other predisposing factors (see Precautions).
Respiratory, Thoracic and Mediastinal Disorders: Rare: Dyspnea.
Gastrointestinal Disorders: Common: Nausea, vomiting, diarrhea, abdominal pain.
Hepatobiliary Disorders: Rare: Reversible rises in bilirubin- and liver-related enzymes. Very Rare: Hepatitis, jaundice.
Skin and Subcutaneous Tissue Disorders: Common: Pruritus, rashes (including photosensitivity). Uncommon: Urticaria. Accelerated diffuse hair loss.
Accelerated diffuse hair loss has been associated with a wide variety of disease processes and medicines, the relationship of the event to acyclovir therapy is uncertain. Rare: Angioedema.
Renal and Urinary Disorders: Rare: Increased blood urea and creatinine. Very Rare: Acute renal failure, renal pain (may be associated with renal failure).
General Disorders and Administration Site Conditions: Common: Fatigue, fever.
Infusion: Blood and Lymphatic System Disorders: Uncommon: Decreased hematological indices (anemia, thrombocytopenia, leukopenia).
Immune System Disorders: Very Rare: Anaphylaxis.
Psychiatric and Nervous System Disorders: Very Rare: Headache, dizziness, agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsions, somnolence, encephalopathy, coma.
The previously mentioned events are generally reversible and usually reported in patients with renal impairment or with other predisposing factors (see Precautions).
Vascular Disorders: Common: Phlebitis.
Respiratory, Thoracic and Mediastinal Disorders: Very Rare: Dyspnea.
Gastrointestinal Disorders: Common: Nausea, vomiting. Very Rare: Diarrhea, abdominal pain.
Hepatobiliary Disorders: Common: Reversible increases in liver-related enzymes. Very Rare: Reversible increases in bilirubin, jaundice, hepatitis.
Skin and Subcutaneous Tissue Disorders: Common: Pruritus, urticaria, rashes (including photosensitivity). Very Rare: Angioedema.
Renal and Urinary Disorders: Common: Increases in blood urea and creatinine. Rapid increases in blood urea and creatinine levels are believed to be related to the peak plasma levels and the state of hydration of the patient. To avoid this effect, Zovirax should not be given as an intravenous bolus injection but by slow IV infusion over a 1-hour period.
Very Rare: Renal impairment, acute renal failure, renal pain. Adequate hydration should be maintained. Renal impairment usually responds rapidly to rehydration of the patient and/or dosage reduction or withdrawal of Zovirax. Progression to acute renal failure, however, can occur in exceptional cases. Renal pain may be associated with renal failure.
General Disorders and Administration Site Conditions: Very Rare: Fatigue, fever, local inflammatory reactions.
Severe local inflammatory reactions sometimes leading to breakdown of the skin have occurred when Zovirax IV for infusion has been inadvertently infused into extracellular tissues.
The following convention has been used for the classification of adverse effects in terms of frequency: Very common ≥1/10, common ≥1/100 and <1/10, uncommon ≥1/1,000 and <1/100, rare ≥1/10,000 and <1/1,000, very rare <1/10,000.
Tablet: Blood and Lymphatic System Disorders: Very Rare: Anemia, leukopenia, thrombocytopenia.
Immune System Disorders: Rare: Anaphylaxis.
Psychiatric and Nervous System Disorders: Common: Headache, dizziness. Very Rare: Agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsions, somnolence, encephalopathy and coma.
The previously mentioned events are generally reversible and usually reported in patients with renal impairment or with other predisposing factors (see Precautions).
Respiratory, Thoracic and Mediastinal Disorders: Rare: Dyspnea.
Gastrointestinal Disorders: Common: Nausea, vomiting, diarrhea, abdominal pain.
Hepatobiliary Disorders: Rare: Reversible rises in bilirubin- and liver-related enzymes. Very Rare: Hepatitis, jaundice.
Skin and Subcutaneous Tissue Disorders: Common: Pruritus, rashes (including photosensitivity). Uncommon: Urticaria. Accelerated diffuse hair loss.
Accelerated diffuse hair loss has been associated with a wide variety of disease processes and medicines, the relationship of the event to acyclovir therapy is uncertain. Rare: Angioedema.
Renal and Urinary Disorders: Rare: Increased blood urea and creatinine. Very Rare: Acute renal failure, renal pain (may be associated with renal failure).
General Disorders and Administration Site Conditions: Common: Fatigue, fever.
Infusion: Blood and Lymphatic System Disorders: Uncommon: Decreased hematological indices (anemia, thrombocytopenia, leukopenia).
Immune System Disorders: Very Rare: Anaphylaxis.
Psychiatric and Nervous System Disorders: Very Rare: Headache, dizziness, agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsions, somnolence, encephalopathy, coma.
The previously mentioned events are generally reversible and usually reported in patients with renal impairment or with other predisposing factors (see Precautions).
Vascular Disorders: Common: Phlebitis.
Respiratory, Thoracic and Mediastinal Disorders: Very Rare: Dyspnea.
Gastrointestinal Disorders: Common: Nausea, vomiting. Very Rare: Diarrhea, abdominal pain.
Hepatobiliary Disorders: Common: Reversible increases in liver-related enzymes. Very Rare: Reversible increases in bilirubin, jaundice, hepatitis.
Skin and Subcutaneous Tissue Disorders: Common: Pruritus, urticaria, rashes (including photosensitivity). Very Rare: Angioedema.
Renal and Urinary Disorders: Common: Increases in blood urea and creatinine. Rapid increases in blood urea and creatinine levels are believed to be related to the peak plasma levels and the state of hydration of the patient. To avoid this effect, Zovirax should not be given as an intravenous bolus injection but by slow IV infusion over a 1-hour period.
Very Rare: Renal impairment, acute renal failure, renal pain. Adequate hydration should be maintained. Renal impairment usually responds rapidly to rehydration of the patient and/or dosage reduction or withdrawal of Zovirax. Progression to acute renal failure, however, can occur in exceptional cases. Renal pain may be associated with renal failure.
General Disorders and Administration Site Conditions: Very Rare: Fatigue, fever, local inflammatory reactions.
Severe local inflammatory reactions sometimes leading to breakdown of the skin have occurred when Zovirax IV for infusion has been inadvertently infused into extracellular tissues.
Drug Interactions
No clinically significant interactions have been identified.
Acyclovir is eliminated primarily unchanged in the urine via active renal tubular secretion. Any drugs administered concurrently that compete with this mechanism may increase acyclovir plasma concentrations. Probenecid and cimetidine increase the AUC of acyclovir by this mechanism and reduce acyclovir renal clearance. Similarly, increases in plasma AUCs of acyclovir and of the inactive metabolite of mycophenolate mofetil, an immunosuppressant agent used in transplant patients have been shown when the drugs are co-administered. However, no dosage adjustment is necessary because of the wide therapeutic index of acyclovir.
Infusion: In patients receiving Zovirax IV, caution is required during concurrent administration with drugs which compete with acyclovir for elimination, because of the potential for increased plasma levels of one or both drugs or their metabolites. Increases in plasma AUCs of acyclovir and of the inactive metabolite of mycophenolate mofetil, an immunosuppressant agent used in transplant patients, have been shown when the drugs are co-administered. Care is also required (with monitoring for changes in renal function) if administering Zovirax with drugs which affect other aspects of renal physiology (eg, cyclosporin, tacrolimus).
Acyclovir is eliminated primarily unchanged in the urine via active renal tubular secretion. Any drugs administered concurrently that compete with this mechanism may increase acyclovir plasma concentrations. Probenecid and cimetidine increase the AUC of acyclovir by this mechanism and reduce acyclovir renal clearance. Similarly, increases in plasma AUCs of acyclovir and of the inactive metabolite of mycophenolate mofetil, an immunosuppressant agent used in transplant patients have been shown when the drugs are co-administered. However, no dosage adjustment is necessary because of the wide therapeutic index of acyclovir.
Infusion: In patients receiving Zovirax IV, caution is required during concurrent administration with drugs which compete with acyclovir for elimination, because of the potential for increased plasma levels of one or both drugs or their metabolites. Increases in plasma AUCs of acyclovir and of the inactive metabolite of mycophenolate mofetil, an immunosuppressant agent used in transplant patients, have been shown when the drugs are co-administered. Care is also required (with monitoring for changes in renal function) if administering Zovirax with drugs which affect other aspects of renal physiology (eg, cyclosporin, tacrolimus).
Caution For Usage
Incompatibilities: None known.
Instructions For Use/Handling: Infusion: The required dose of Zovirax IV for infusion should be administered by slow IV infusion over a 1-hour period.
Zovirax IV for infusion should be reconstituted using the following volumes of either water for injections or sodium chloride injection (0.9% w/v) to provide a solution containing Zovirax 25 mg/mL (see Table 3).
Instructions For Use/Handling: Infusion: The required dose of Zovirax IV for infusion should be administered by slow IV infusion over a 1-hour period.
Zovirax IV for infusion should be reconstituted using the following volumes of either water for injections or sodium chloride injection (0.9% w/v) to provide a solution containing Zovirax 25 mg/mL (see Table 3).
From the calculated dose, determine the appropriate number and strength of vials to be used. To reconstitute each vial, add the
recommended volume of infusion fluid and shake gently until the contents of the vial have dissolved completely. After reconstitution Zovirax IV for infusion may be administered by a controlled-rate infusion pump.
Alternatively, the reconstituted solution may be further diluted to give Zovirax IV concentration of not >5 mg/mL (0.5% w/v) for administration by infusion: Add the required volume of reconstituted solution to the chosen infusion solution, as recommended in the following, and shake well to ensure adequate mixing occurs.
For children and neonates, where it is advisable to keep the volume of infusion fluid to a minimum, it is recommended that dilution is on the basis of 4 mL reconstituted solution Zovirax IV 100 mg added to 20 mL of infusion fluid.
For adults, it is recommended that infusion bags containing 100 mL of infusion fluid are used, even when this would give Zovirax IV concentration substantially <0.5% w/v. Thus, one 100 mL infusion bag may be used for any dose between 250 mg and 500 mg Zovirax IV (10 mL and 20 mL of reconstituted solution) but a 2nd bag must be used for doses between 500 mg and 1,000 mg.
When diluted in accordance with the recommended schedules, Zovirax IV for infusion is known to be compatible with the following infusion fluids and stable for up to 12 hours at room temperature (15-25°C): Sodium chloride IV infusion BP (0.45% and 0.9% w/v); sodium chloride (0.18% w/v) and glucose (4% w/v) IV infusion BP; sodium chloride (0.45% w/v) and glucose (2.5% w/v) IV infusion BP; compound sodium lactate IV Infusion BP (Hartmann's solution).
Zovirax IV for infusion when diluted in accordance with the previously mentioned schedule will give Zovirax IV concentration not greater than 0.5% w/v.
When reconstituted as directed, Zovirax IV for infusion has a pH of approximately 11.
Since no antimicrobial preservative is included, reconstitution and dilution must be carried out under full aseptic conditions, immediately before use, and any unused solution should be discarded.
Reconstituted or diluted solutions should not be refrigerated.
Should any visible turbidity or crystallization appear in the solution before or during infusion, the preparation should be discarded.
Alternatively, the reconstituted solution may be further diluted to give Zovirax IV concentration of not >5 mg/mL (0.5% w/v) for administration by infusion: Add the required volume of reconstituted solution to the chosen infusion solution, as recommended in the following, and shake well to ensure adequate mixing occurs.
For children and neonates, where it is advisable to keep the volume of infusion fluid to a minimum, it is recommended that dilution is on the basis of 4 mL reconstituted solution Zovirax IV 100 mg added to 20 mL of infusion fluid.
For adults, it is recommended that infusion bags containing 100 mL of infusion fluid are used, even when this would give Zovirax IV concentration substantially <0.5% w/v. Thus, one 100 mL infusion bag may be used for any dose between 250 mg and 500 mg Zovirax IV (10 mL and 20 mL of reconstituted solution) but a 2nd bag must be used for doses between 500 mg and 1,000 mg.
When diluted in accordance with the recommended schedules, Zovirax IV for infusion is known to be compatible with the following infusion fluids and stable for up to 12 hours at room temperature (15-25°C): Sodium chloride IV infusion BP (0.45% and 0.9% w/v); sodium chloride (0.18% w/v) and glucose (4% w/v) IV infusion BP; sodium chloride (0.45% w/v) and glucose (2.5% w/v) IV infusion BP; compound sodium lactate IV Infusion BP (Hartmann's solution).
Zovirax IV for infusion when diluted in accordance with the previously mentioned schedule will give Zovirax IV concentration not greater than 0.5% w/v.
When reconstituted as directed, Zovirax IV for infusion has a pH of approximately 11.
Since no antimicrobial preservative is included, reconstitution and dilution must be carried out under full aseptic conditions, immediately before use, and any unused solution should be discarded.
Reconstituted or diluted solutions should not be refrigerated.
Should any visible turbidity or crystallization appear in the solution before or during infusion, the preparation should be discarded.
Storage
Store at temperatures not exceeding 30°C.
Action
Pharmacotherapeutic Group: Antiviral agent.
Pharmacology: Pharmacodynamics: Mechanism of Action: Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against human herpes viruses, including herpes simplex virus (HSV) types 1 and 2, varicella-zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In cell culture, acyclovir has the greatest antiviral activity against HSV-1, followed (in decreasing order of potency) by HSV-2, VZV, EBV and CMV.
The inhibitory activity of acyclovir for HSV-1, HSV-2, VZV, EBV and CMV is highly selective. The enzyme thymidine kinase (TK) of normal, non-infected cells does not use acyclovir effectively as a substrate, hence toxicity to mammalian host cells is low; however, TK encoded by HSV, VZV and EBV converts acyclovir to acyclovir monophosphate, a nucleoside analogue, which is further converted to the diphosphate and finally to the triphosphate by cellular enzymes. Acyclovir triphosphate interferes with the viral DNA polymerase and inhibits viral DNA replication with resultant chain termination following its incorporation into the viral DNA.
Pharmacodynamic Effects: Prolonged or repeated courses of acyclovir in severely immuno-compromised individuals may result in the selection of virus strains with reduced sensitivity, which may not respond to continued acyclovir treatment.
Most of the clinical isolates with reduced sensitivity have been relatively deficient in viral TK however, strains with altered viral TK or viral DNA polymerase have also been reported. In vitro exposure of HSV isolates to acyclovir can also lead to the emergence of less sensitive strains. The relationship between the in vitro-determined sensitivity of HSV isolates and clinical response to acyclovir therapy is not clear.
All patients should be cautioned to ensure they avoid the potential of virus transmission, particularly when active lesions are present.
Pharmacokinetics: Absorption: In adults, mean steady-state peak plasma concentration (Cssmax) levels following a 1-hour infusion of 2.5 mg/kg, 5 mg/kg and 10 mg/kg and 15 mg/kg were 22.7 micromolar (mcM) (5.1 mcg/mL), 43.6 mcM (9.8 mcg/mL), 92 mcM (20.7 mcg/mL) and 105 mcM (23.6 mcg/mL), respectively. The corresponding trough plasma levels (Cssmin) levels 7 hours later were 2.2 mcM (0.5 mcg/mL), 3.1 mcM (0.7 mcg/mL), 10.2 mcM (2.3 mcg/mL) and 8.8 mcM (2 mcg/mL), respectively. In children >1 year, similar mean Cssmax and Cssmin levels were observed when a dose of 250 mg/m2 was substituted for 5 mg/kg and a dose of 500 mg/m2 was substituted for 10 mg/kg. In neonates (0-3 months) treated with doses of 10 mg/kg administered by infusion over a 1-hr period every 8 hours, the Cssmax was found to be 61.2 mcM (13.8 mcg/mL) and the Cssmin to be 10.1 mcM (2.3 mcg/mL). A separate group of neonates treated with 15 mg/kg every 8 hours showed approximate dose proportional increases, with a Cmax of 83.5 mcM (18.8 mcg/mL) and Cmin of 14.1 mcM (3.2 mcg/mL).
Tablet: Acyclovir is only partially absorbed from the gut. Mean Cssmax following doses of 200 mg administered 4 hrly were 3.1 mcM (0.7 mcg/mL) and equivalent Cssmin were 1.8 mcM (0.4 mcg/mL). Corresponding Cssmax levels following doses of 400 mg and 800 mg administered 4 hrly were 5.3 mcM (1.2 mcg/mL) and 8 mcM (1.8 mcg/mL), respectively, and equivalent Cssmin levels were 2.7 mcM (0.6 mcg/mL) and 4 mcM (0.9 mcg/mL).
Distribution: Cerebrospinal fluid levels are approximately 50% of corresponding plasma levels. Plasma protein-binding is relatively low (9-33%) and drug interactions involving binding site displacement are not anticipated.
Elimination: In adults, the terminal plasma half-life of acyclovir after administration of IV acyclovir is about 2.9 hours. Most of the drug is excreted unchanged by the kidney. Renal clearance of acyclovir is substantially greater than creatinine clearance, indicating that tubular secretion in addition to glomerular filtration contributes to the renal elimination of the drug. 9-Carboxymethoxy-methylguanine is the only significant metabolite of acyclovir and accounts for approximately 10-15% of the dose excreted in the urine. When acyclovir is given 1 hour after 1 g of probenecid, the terminal half-life and the area under plasma concentration-time curve (AUC) is extended by 18% and 40%, respectively.
In neonates (0-3 months) treated with doses of 10 mg/kg administered by infusion over a 1-hour period every 8 hours, the terminal plasma half-life was 3.8 hours.
Special Patient Populations: In patients with chronic renal failure, the mean terminal half-life was found to be 19.5 hours. The mean acyclovir half-life during hemodialysis was 5.7 hours. Plasma acyclovir levels dropped approximately 60% during dialysis.
In the elderly, total body clearance falls with increasing age associated with decreases in creatinine clearance, although there is little change in the terminal plasma half-life.
Tablet: Studies have shown no apparent changes in the pharmacokinetic behaviour of acyclovir or zidovudine when both are administered simultaneously to HIV infected patients.
Clinical Studies: There is no information on the effect of Zovirax IV for infusion on human female fertility. In a study of 20 male patients with normal sperm count, oral acyclovir administered at doses of up to 1 g/day for up to 6 months has been shown to have no clinically significant effect on sperm count, motility or morphology.
Toxicology: Preclinical Safety Data: The results of a wide range of mutagenicity tests in vitro and in vivo indicate that acyclovir does not pose a genetic risk to man.
Acyclovir was not carcinogenic in long-term studies in the rat and the mouse.
Largely reversible adverse effects on spermatogenesis in association with overall toxicity in rats and dogs have been reported only at doses of acyclovir greatly in excess of those employed therapeutically. Two (2)-generation studies in mice did not reveal any effect of orally administered acyclovir on fertility.
Systemic administration of acyclovir in internationally accepted standard tests did not produce embryotoxic or teratogenic effects in rabbits, rats or mice. In a nonstandard test in rats, fetal abnormalities were observed but only following such high subcutaneous doses that maternal toxicity was produced. The clinical relevance of these findings is uncertain.
Pharmacology: Pharmacodynamics: Mechanism of Action: Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against human herpes viruses, including herpes simplex virus (HSV) types 1 and 2, varicella-zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In cell culture, acyclovir has the greatest antiviral activity against HSV-1, followed (in decreasing order of potency) by HSV-2, VZV, EBV and CMV.
The inhibitory activity of acyclovir for HSV-1, HSV-2, VZV, EBV and CMV is highly selective. The enzyme thymidine kinase (TK) of normal, non-infected cells does not use acyclovir effectively as a substrate, hence toxicity to mammalian host cells is low; however, TK encoded by HSV, VZV and EBV converts acyclovir to acyclovir monophosphate, a nucleoside analogue, which is further converted to the diphosphate and finally to the triphosphate by cellular enzymes. Acyclovir triphosphate interferes with the viral DNA polymerase and inhibits viral DNA replication with resultant chain termination following its incorporation into the viral DNA.
Pharmacodynamic Effects: Prolonged or repeated courses of acyclovir in severely immuno-compromised individuals may result in the selection of virus strains with reduced sensitivity, which may not respond to continued acyclovir treatment.
Most of the clinical isolates with reduced sensitivity have been relatively deficient in viral TK however, strains with altered viral TK or viral DNA polymerase have also been reported. In vitro exposure of HSV isolates to acyclovir can also lead to the emergence of less sensitive strains. The relationship between the in vitro-determined sensitivity of HSV isolates and clinical response to acyclovir therapy is not clear.
All patients should be cautioned to ensure they avoid the potential of virus transmission, particularly when active lesions are present.
Pharmacokinetics: Absorption: In adults, mean steady-state peak plasma concentration (Cssmax) levels following a 1-hour infusion of 2.5 mg/kg, 5 mg/kg and 10 mg/kg and 15 mg/kg were 22.7 micromolar (mcM) (5.1 mcg/mL), 43.6 mcM (9.8 mcg/mL), 92 mcM (20.7 mcg/mL) and 105 mcM (23.6 mcg/mL), respectively. The corresponding trough plasma levels (Cssmin) levels 7 hours later were 2.2 mcM (0.5 mcg/mL), 3.1 mcM (0.7 mcg/mL), 10.2 mcM (2.3 mcg/mL) and 8.8 mcM (2 mcg/mL), respectively. In children >1 year, similar mean Cssmax and Cssmin levels were observed when a dose of 250 mg/m2 was substituted for 5 mg/kg and a dose of 500 mg/m2 was substituted for 10 mg/kg. In neonates (0-3 months) treated with doses of 10 mg/kg administered by infusion over a 1-hr period every 8 hours, the Cssmax was found to be 61.2 mcM (13.8 mcg/mL) and the Cssmin to be 10.1 mcM (2.3 mcg/mL). A separate group of neonates treated with 15 mg/kg every 8 hours showed approximate dose proportional increases, with a Cmax of 83.5 mcM (18.8 mcg/mL) and Cmin of 14.1 mcM (3.2 mcg/mL).
Tablet: Acyclovir is only partially absorbed from the gut. Mean Cssmax following doses of 200 mg administered 4 hrly were 3.1 mcM (0.7 mcg/mL) and equivalent Cssmin were 1.8 mcM (0.4 mcg/mL). Corresponding Cssmax levels following doses of 400 mg and 800 mg administered 4 hrly were 5.3 mcM (1.2 mcg/mL) and 8 mcM (1.8 mcg/mL), respectively, and equivalent Cssmin levels were 2.7 mcM (0.6 mcg/mL) and 4 mcM (0.9 mcg/mL).
Distribution: Cerebrospinal fluid levels are approximately 50% of corresponding plasma levels. Plasma protein-binding is relatively low (9-33%) and drug interactions involving binding site displacement are not anticipated.
Elimination: In adults, the terminal plasma half-life of acyclovir after administration of IV acyclovir is about 2.9 hours. Most of the drug is excreted unchanged by the kidney. Renal clearance of acyclovir is substantially greater than creatinine clearance, indicating that tubular secretion in addition to glomerular filtration contributes to the renal elimination of the drug. 9-Carboxymethoxy-methylguanine is the only significant metabolite of acyclovir and accounts for approximately 10-15% of the dose excreted in the urine. When acyclovir is given 1 hour after 1 g of probenecid, the terminal half-life and the area under plasma concentration-time curve (AUC) is extended by 18% and 40%, respectively.
In neonates (0-3 months) treated with doses of 10 mg/kg administered by infusion over a 1-hour period every 8 hours, the terminal plasma half-life was 3.8 hours.
Special Patient Populations: In patients with chronic renal failure, the mean terminal half-life was found to be 19.5 hours. The mean acyclovir half-life during hemodialysis was 5.7 hours. Plasma acyclovir levels dropped approximately 60% during dialysis.
In the elderly, total body clearance falls with increasing age associated with decreases in creatinine clearance, although there is little change in the terminal plasma half-life.
Tablet: Studies have shown no apparent changes in the pharmacokinetic behaviour of acyclovir or zidovudine when both are administered simultaneously to HIV infected patients.
Clinical Studies: There is no information on the effect of Zovirax IV for infusion on human female fertility. In a study of 20 male patients with normal sperm count, oral acyclovir administered at doses of up to 1 g/day for up to 6 months has been shown to have no clinically significant effect on sperm count, motility or morphology.
Toxicology: Preclinical Safety Data: The results of a wide range of mutagenicity tests in vitro and in vivo indicate that acyclovir does not pose a genetic risk to man.
Acyclovir was not carcinogenic in long-term studies in the rat and the mouse.
Largely reversible adverse effects on spermatogenesis in association with overall toxicity in rats and dogs have been reported only at doses of acyclovir greatly in excess of those employed therapeutically. Two (2)-generation studies in mice did not reveal any effect of orally administered acyclovir on fertility.
Systemic administration of acyclovir in internationally accepted standard tests did not produce embryotoxic or teratogenic effects in rabbits, rats or mice. In a nonstandard test in rats, fetal abnormalities were observed but only following such high subcutaneous doses that maternal toxicity was produced. The clinical relevance of these findings is uncertain.
MedsGo Class
Antivirals
Features
Brand
Zovirax
Full Details
Dosage Strength
250mg
Drug Ingredients
- Acyclovir
Drug Packaging
Powder for Injection (I.V.) 1's
Generic Name
Acyclovir
Dosage Form
Powder For Injection (I.V.)
Registration Number
DR-XY1599
Drug Classification
Prescription Drug (RX)
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