Acycloguanosine

Uses

Acycloguanosine IV for Infusion is used for the treatment of- Herpes Zoster, Genital Herpes, Chickenpox, Herpes Simplex Infections, Herpes Simplex Encephalitis

Acycloguanosine eye ointment is used for treatment of Herpes Simplex Keratitis.

Acycloguanosine Oral is used for Herpes Zoster Genital Herpes, Chickenpox, Herpes Simplex Infections, Herpes Simplex Encephalitis

Acycloguanosine cream are used for the treatment of herpes simplex virus infections of the skin including initial and recurrent genital herpes and herpes labialis.

Acycloguanosine is also used to associated treatment for these conditions: Bell's Palsy, Chickenpox, Cytomegalovirus (CMV) Infection, Encephalitis, Herpes Simplex, Herpes Simplex Infection, Herpes Zoster, Herpes simplex of the oral-labial, Herpes simplex type I reactivation, Recurrent Genital Herpes (RGH), Recurrent Herpes Labialis, VZV re-activation, Acute Genital herpes, Acute Herpes labialis, Acute Herpetic keratitis, Severe Genital herpes

How Acycloguanosine works

Acycloguanosine is becomes acyclovir monophosphate due to the action of viral thymidine kinase. Acycloguanosine monophosphate is converted to the diphosphate form by guanylate kinase. Acycloguanosine diphosphate is converted to acyclovir triphosphate by nucleoside diphosphate kinase, pyruvate kinase, creatine kinase, phosphoglycerate kinase, succinyl-CoA synthetase, phosphoenolpyruvate carboxykinase and adenylosuccinate synthetase. Acycloguanosine triphosphate has higher affinity for viral DNA polymerase than cellular DNA polymerase and incorporates into the DNA where the missing 2' and 3' carbons causes DNA chain termination. In other cases acyclovir triphosphate competes so strongly for viral DNA polymerase that other bases cannot associate with the enzyme, inactivating it.

Dosage

Acycloguanosine dosage

Apply ointment into lower conjunctival sac five times daily at 4 hours interval; continue for minimum 3 days after healing.

Acycloguanosine cream should be applied to lesions or impending lesions 5 times daily (at 4 hourly intervals omitting the night-time dose). Treatment should continue for 5 days. If healing does not occur, treatment may be extended for up to 10 days.

The total daily dosage of Aciclovir should be based on the type or severity of infection and given in equally divided doses based on consideration of degree of susceptibility of the pathogens, renal function and body-weight.

Aciclovir Tablet

• Acute Herpes Zoster:

800 mg every 4 hours, 5 times daily for 7 to 10 days.

• Genital Herpes:

Initial Genital Herpes: 200 mg every 4 hours, 5 times daily for 10 days.

Chronic suppressive therapy for recurrent disease: 400 mg 2 times daily for up to 12 months.

Intermittent therapy: 200 mg every 4 hours, 5 times daily for 5 days.

• Chickenpox:

Children (2 years of age and older): 20 mg/kg/dose 4 times daily (80 mg/kg/day) for 5 days.

Adults and Children (>40 kg): 800 mg 4 times daily for 5 days.

Aciclovir IV

The required dose of Aciclovir IV should be administered by slow intravenous infusion over a one-hour period.

• Herpes Simplex (HSV-1 and HSV-2) Infections:

Adults and Adolescents (≥12 years): 5 mg/kg, 8 hourly for 7 days.

Pediatrics (<12 years): 10 mg/kg 8 hourly for 7 days.

• Severe Initial Herpes Genitalis:

Adults and Adolescents (≥12 years): 5 mg/kg 8 hourly for 5 days.

• Herpes Simplex Encephalitis:

Adults and Adolescents (≥12 years): 10 mg/kg 8 hourly for 10 days.

Pediatrics (3 months to 12 years of age): 20 mg/kg 8 hourly for 10 days.

• Neonatal Herpes Simplex (Birth to 3 months):

10 mg/kg 8 hourly for 10 days.

• Varicella Zoster:

Adults and Adolescents (≥12 years): 10 mg/kg 8 hourly for 7 days.

Pediatrics (<12 years): 20 mg/kg 8 hourly for 7 days.

Dose adjustment of Tablet for patients with acute or chronic renal impairment, based on Creatinine Clearance, Cr Cl (mL/min/1.73 m2):

For Cr Cl= > 25 : 800 mg 4 hourly 5 times daily

For Cr Cl = 10 to 25 : 200 mg 4 hourly 5 times daily or 400 mg 12 hourly or 800 mg 8 hourly

For Cr Cl = 0 to 10 : 200 mg 12 hourly or 400 mg 12 hourly or 800 mg 12 hourly

Dose adjustment of IV for patients with acute or chronic renal impairment, based on Creatinine Clearance, Cr Cl (mL/min/1.73 m2):

For Cr Cl = > 50 : 100% of recommended dose, 8 hourly

For Cr Cl = 25 to 50 : 100% of recommended dose, 12 hourly

For Cr Cl = 10 to 25 : 100% of recommended dose, 24 hourly

For Cr Cl = 0 to 10 : 50% of recommended dose, 24 hourly

Caution: Rapid or bolus intravenous injection must be avoided. Intramuscular or subcutaneous injection must be avoided.

Reconstitution procedure of IV infusion

Vial containing 250 mg Aciclovir will be reconstituted with 50 ml infusion solution and vial containing 500 mg Aciclovir will be reconstituted with 100 ml infusion solution. Besides, Vial containing 1 gm Aciclovir will be reconstituted with 250 ml infusion solution. 10 ml of the infusion solution will be added to the vial containing 250 mg, 500 mg and 1 gm Aciclovir. Shake well and transfer the required amount of solution to the infusion container. The final concentration of Aciclovir will be not more than 5 mg/ml.

The reconstituted solution should be used within 12 hours. Refrigeration of reconstituted solution may result in the formation of a precipitate which will re-dissolve at room temperature.

Compatible infusion fluids

Sodium Chloride Intravenous Infusion BP (0.45% and 0.9% w/v)

Sodium Chloride (0.18% w/v) and Glucose (4% w/v) Intravenous Infusion BP

Sodium Chloride (0.45% w/v) and Glucose (2.5% w/v) Intravenous Infusion BP

Hartmann's Solution

It is recommended that Acycloguanosine IV Injection for Intravenous Infusion should be administered for five to seven days in the treatment of most infections and for at least ten days in the treatment of Herpes simplex encephalitis.

Each 250 mg vial of Acycloguanosine IV Injection should be reconstituted by the addition of 10 ml of either Water for Injection or Sodium Chloride Intravenous Infusion (0.9% w/v). This provides a solution containing 25 mg Acycloguanosine per ml.

Each 500 mg vial of Acycloguanosine IV Injection should be reconstituted by the addition of 10 ml of either Water for Injection or Sodium Chloride Intravenous Infusion (0.9% w/v). This provides a solution containing 50 mg Acycloguanosine per ml.

Side Effects

Transient mild stinging immediately following application may occur in a small proportion of patients. Local irritation and inflammation such as blepharitis and conjunctivitis have also been reported.

Skin rashes which, resolve after withdrawal of the drug have been reported with acyclovir. The most common adverse effect is mild pain including transient burning and stinging at the site of application following acyclovir cream.

Toxicity

Symptoms of overdose include agitation, coma, seizures, lethargy, and precipitation in renal tubules. These symptoms are more common in patients given high doses without monitoring of fluid and electrolyte balance or reduced kidney function. In the case of an overdose, treat with symptomatic and supportive care.

Precaution

Aciclovir should be administered with caution in patient with renal impairment and doses should be adjusted according to creatinine clearance.

Renal impairment. Pregnancy, lactation. Neurological abnormalities with significant hypoxia, serious hepatic or electrolyte abnormalities. Maintain adequate hydration.

Acycloguanosine cream is not recommended for application to mucous membrane such as eye, mouth, vagina etc.

Interaction

Concomitant administration of probenecid and acyclovir has reportedly increased the mean plasma half-life and decreased urinary excretion and renal clearance of acyclovir. Amphotericin B has been shown to potentiate the antiviral effect of acyclovir against pseudorabies virus in vitro when both drugs are added to the culture medium. Ketoconazole and acyclovir have shown dose-dependent, synergistic, antiviral activity against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) in in-vitro replication studies.

Food Interaction

• Drink plenty of fluids. Dehydration with acyclovir predisposes patients to nephrotoxicity.
• Take with or without food. The absorption is unaffected by food.

Acycloguanosine Drug Interaction

Unknown: aspirin, aspirin, duloxetine, duloxetine, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, pregabalin, pregabalin, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol, alprazolam, alprazolam, cetirizine, cetirizine

Acycloguanosine Disease Interaction

Major: renal dysfunctionModerate: dehydration, hemodialysis, neurotoxicity

Volume of Distribution

The volume of distribution of acyclovir is 0.6L/kg.

Elimination Route

The oral bioavailability of acyclovir is 10-20% but decreases with increasing doses. Acycloguanosine ointment is 12 Acycloguanosine buccal tablets and ophthalmic ointment are minimally absorbed. The bioavailability of acyclovir is not affected by food.

Acycloguanosine has a mean T_max of 1.1±0.4 hours, mean C_max of 593.7-656.5ng/mL, and mean AUC of 2956.6-3102.5h*ng/mL.

Half Life

The clearance of acyclovir varies from 2.5-3 hours depending on the creatinine clearance of the patient. The plasma half life of acyclovir during hemodialysis is approximately 5 hours. The mean half life in patients from 7 months to 7 years old is 2.6 hours.

Clearance

The renal clearance of acyclovir is 248mL/min/1.73m. The total clearance in neonates if 105-122mL/min/1.73m

Elimination Route

The majority of acyclovir is excreted in the urine as unchanged drug. 90-92% of the drug can be excreted unchanged through glomerular filtration and tubular secretion. 2.

Pregnancy & Breastfeeding use

Pregnancy category B. There are no adequate and well-controlled studies in pregnant women. Acycloguanosine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Use in nursing mothers: Acycloguanosine should be administered to a nursing mother with caution and only when indicated. Geriatric Use: No overall differences in safety are observed between older and younger subjects.

The use of Acycloguanosine sterile eye ointment should be considered only when the potential benefits outweigh the possibility of unknown risk.

Contraindication

Acycloguanosine IV Injection is contraindicated in patients known to be hypersensitive to Acycloguanosine or Valacyclovir.

Acycloguanosine ophthalmic is contraindicated to the patients with known hypersensitivity to acyclovir.

Acycloguanosine oral is contraindicated in patients known to be hypersensitive to acyclovir. For the patients with severe renal impairment, a reduction of the doses is recommended.

Acycloguanosine cream is contraindicated in patients known to be hypersensitive to acyclovir.

Special Warning

The dose of Acycloguanosine IV injection in children aged 1-12 years should be calculated on the basis of body surface area. Children in this age group with Herpes simplex infections (except Herpes simplex encephalitis) or Varicella zoster infections should be given Acycloguanosine Infusion in doses of 250 mg per square metre of body surface area (equivalent to 5 mg/kg in adults). Immunocompromised children in this age group with Varicella zoster virus infection or with Herpes simplex encephalitis should be given Acycloguanosine IV Infusion in doses of 500 mg per square metre of body surface area (equivalent to 10 mg/kg in adults). Children with impaired renal function require an appropriately modified dose, according to the degree of impairment.

HSV infections in children over 2 years should be given adult doses and children below 2 years should be given half of the adult dose.

Acute Overdose

Symptoms: Elevations in BUN and serum creatinine, subsequent renal failure, anuria, agitation, coma, lethargy, seizures.

Management: Consider use of haemodialysis until renal function is restored.

Interaction with other Medicine

Probenecid reduces Aciclovir excretion and so increases plasma concentration and risk of toxicity.

Storage Condition

Store at 15°C to 25°C. Protected from light and moisture. Keep the medicine out of the reach of children.

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