Vilerm

VILERM (200 MG TABLET): Each tablet contains Acyclovir (INN: Aciclovir) 200 mg.
VILERM (400 MG TABLET): Each tablet contains Acyclovir (INN: Aciclovir) 400 mg.
VILERM (800 MG TABLET): Each tablet contains Acyclovir (INN: Aciclovir) 800 mg.
VILERM IV INFUSION 250 MG: Each vial of VILERM IV INFUSION 250 MG contains Acyclovir sodium (INN: Aciclovir) equivalent to Acyclovir 250 mg as a sterile Freeze-dried powder.
The sodium content is 93.2 mg (4.05 mmole) per gram of Acyclovir.
VILERM IV INFUSION 500 MG: Each vial of VILERM IV INFUSION 500 MG contains Acyclovir sodium (INN: Aciclovir) equivalent to Acyclovir 500 mg as a sterile lyophilized powder.
The sodium content is 93.2 mg (4.05 mmole) per gram of Acyclovir.

Pharmacology: Pharmacodynamics: Tablet: Acyclovir is a synthetic purine nucleoside analogue antiviral agent with in vitro and in vivo inhibitory activity against herpes simplex virus (HSV) types I and II, varicella zoster virus, Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Acyclovir has the greatest antiviral activity against HSV type I followed (in decreasing order of potency) by HSV type II, VZV, EBV and CMV. Acyclovir exerts its antiviral effect by interfering with DNA synthesis and inhibiting viral replication. The antiviral activity of Acyclovir appears to depend principally on the intracellular conversion of the drug to Acyclovir triphosphate. In cells infected with herpesvirus in vitro, Acyclovir is converted to Acyclovir monophosphate principally via virus-coded thymidine kinase (TK); the monophosphate is phosphorylated to the diphosphate via cellular guanylate kinase and then to the triphosphate via other cellular enzymes. Acyclovir triphosphate inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and being incorporated into viral DNA. These causes termination of the growing viral DNA chain and inactivation of the viral DNA polymerase.
Powder for infusion: Acyclovir is a synthetic purine nucleoside analogue with in vitro inhibitory activity against herpes simplex virus (HSV) types 1 and 2, varicella zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). 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 these viruses 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 Acyclovir triphosphate incorporation into the viral DNA.
Pharmacokinetics: Tablet: Absorption of Acyclovir from gastrointestinal tract is incomplete. Plasma Acyclovir concentrations were not dose proportional over the oral dosing. Bioavailability of oral Acyclovir is about 10 to 20%. Food does not appear to affect absorption of Acyclovir. Peak plasma concentrations of Acyclovir usually occur within 1.5-2.5 hours after oral administration. Acyclovir 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. Acyclovir is approximately 9-33% bound to plasma proteins. Acyclovir crosses the placenta and is distributed into breast milk. Acyclovir is metabolized partially to 9-carboxymethoxymethylguanine and minimally to 8-hydroxy-9-(2-hydroxyethoxymethyl)guanine. Acyclovir is excreted largely unchanged in the urine. Fecal excretion may account for about 2% of a dose. Acyclovir is removed by hemodialysis.
Powder for infusion: When Acyclovir was administered by intravenous infusion, Acyclovir is widely distributed into body tissues and fluids in the body including the brain, kidney, saliva, lung, liver, muscle, spleen, uterus, vaginal mucosa and secretions, cerebrospinal fluid (CSF) and herpetic vesicular fluid. Following IV infusion, Acyclovir generally diffuses well into CSF. In patients with uninflamed meninges, CSF concentrations of Acyclovir are reported to be approximately 50% of concurrent serum Acyclovir concentrations. Plasma protein binding is relatively low (9 to 33%). Acyclovir crosses the placenta and is distributed in breast milk. Acyclovir is metabolized partially to 9-carboxymethoxymethylguanine and minimally to 8-hydroxy-9-(2-hydroxyethoxymethyl)guanine. Acyclovir is excreted largely unchanged in the urine and Acyclovir is excreted through feces.
Acyclovir is removed by hemodialysis.

Tablet: Treatment of herpes simplex virus (HSV) infections of the skin and mucous membrane including treatment of initial episodes and the management of recurrent episodes of genital herpes.
For the suppression (prevention of recurrences) of recurrent herpes simplex infections in immunocompetent patient and for the prophylaxis of herpes simplex infections in immunocompromised patients.
Treatment of varicella infections (Chickenpox).
Treatment of herpes zoster (Shingles).
Prophylaxis of CMV infection in bone marrow transplant recipients. The administration of one month's treatment with Acyclovir IV infusion followed by 6 months treatment with high dose oral Acyclovir reduced the mortality rate after transplantation.
Powder for infusion: VILERM IV INFUSION is indicated for treatment and prevention of the following infections caused by susceptible viruses: 1. Treatment of herpes simplex infections.
2. Prophylaxis of herpes simplex infections in immune-compromised patients.
3. Treatment of varicella zoster infections (Chickenpox and Shingles).
4. Treatment of herpes simplex infections in the neonate.
5. Prophylaxis of cytomegalovirus (CMV) infection in bone marrow transplant recipients. It has been shown that high dose Acyclovir IV infusion reduces the incidence and delays the onset of CMV infection. When high dose Acyclovir IV infusion is followed by 6 months treatment with high dose oral Acyclovir, mortality and the incidence of viraemia are also reduced.

Tablet: Acyclovir should be given as soon as possible after symptoms appear. Therapy should be initiated at the earliest sign or symptom (prodrome) of recurrence.
Food does not appear to affect oral absorption of Acyclovir, and the drug may be administered without regard to meals.
The dose and duration of administration depend on severity of the infection and the patient's condition.
Acyclovir should be taken continuously for the specified period or Acyclovir should be used as prescribed by the physician.
Adults: Herpes simplex infections: 200 mg orally 5 times daily (usually every 4 hours while awake) for 5-10 days.
In severe infections, the physician may consider increasing the dose and duration.
400 mg orally 5 times daily (usually every 4 hours while awake) for 7-14 days or as prescribed by the physician.
Chronic suppressive and maintenance prophylaxis of herpes simplex: 200 mg 4 times daily or 400 mg orally twice daily or as prescribed by the physician.
In severe HIV-infected patients, 400 mg orally 3 times daily for 7-14 days or may switch to intravenous therapy.
Genital herpes simplex infections initial episodes: 200 mg orally 5 times daily (usually every 4 hours while awake) for 10 days or as prescribed by the physician.
Episodic treatment of recurrent genital herpes simplex. Acyclovir should be initiated at the earliest prodromal sign or symptom of recurrence: 200 mg orally 5 times daily (usually every 4 hours while awake) for 5 days or as prescribed by the physician.
Chronic suppressive therapy of recurrent episodes: 400 mg orally 2 times daily for up to 12 months or as prescribed by the physician. Therapy should be interrupted every 6 to 12 months for reassessment of the condition. Dosage reduction to 400 to 600 mg orally daily can be tried.
Varicella (chickenpox): 800 mg orally 4 times daily for 5 days.
Herpes Zoster (Shingles): 800 mg orally 5 times daily (usually every 4 hours while awake) for 7-10 days.
Severely immunocompromised patients: Herpes simplex infections: 400 mg orally 5 times daily (usually every 4 hours while awake) for 7-14 days.
Episodic treatment of recurrent genital Herpes simplex. Acyclovir should be initiated at the earliest prodromal sign or symptom of recurrence: 400 mg orally 3 times daily for 5-14 days.
Chronic suppressive therapy of recurrent episodes: 400 mg orally 2 times daily; continue indefinitely regardless of CD₄ count in patients with severe recurrences of genital herpes or in patients who want to minimize frequency of recurrences or 400-800 mg 2-3 times daily.
Varicella (chickenpox): 800 mg orally 5 times daily for 5-7 days.
Herpes zoster (Shingles): 800 mg orally 5 times daily for 7-10 days.
Prophylaxis of CMV infection in bone marrow transplant recipients: In the management of bone marrow recipients this would normally be preceded by up to one month's therapy with intravenous Acyclovir [500 mg/m² of body surface area (3 times daily) every 8 hours (5 days before up to 30 days after transplant)]. The patients received intravenous Acyclovir followed by oral Acyclovir. The duration of oral Acyclovir treatment in bone marrow recipients was 6 months (from 1 to 7 months post-transplant) [800 mg orally 4 times daily].
Children: Treatment and suppressive therapy in immunocompromised patients: Treatment: 20 mg/kg/dose orally 3 times daily for 7-14 days. Maximum dose 400 mg/dose.
Suppressive therapy: 20 mg/kg/dose orally 2 times daily. Maximum dose 800 mg/dose. Reassess after 12 months.
Varicella (chickenpox): 2 years and older: 20 mg/kg/dose orally 4 times daily (80 mg/kg per day) for 5 days, or as prescribed by the physician.
2 years and older, more than 40 kg: usual adult dose (800 mg orally 4 times daily for 5 days).
Prophylaxis of CMV infection in bone marrow transplant recipients: Prophylaxis of CMV infection in children, over 2 years of age, who have undergone bone marrow transplantation, the adult dose may be given.
Administration in hepatic impairment: Acyclovir should be used with caution in hepatic impairment.
Administration in renal impairment: Doses of Acyclovir should be reduced in renal impairment according to creatinine clearance. (See Table 1.)

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Because Acyclovir is removed by hemodialysis. The patients undergoing hemodialysis receive a supplemental oral dose of the drug immediately after each dialysis period. The supplemental doses of oral Acyclovir do not appear to be necessary following peritoneal dialysis.
For immunocompromised patients with impaired renal function: A usual dosage regimen is 200-800 mg every 4-6 hours. Adjusted dosage regimen based on the patient's creatinine. (See Table 2.)

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Patients undergoing hemodialysis receive a supplemental oral dose of the drug immediately after each dialysis period.
Elderly: Acyclovir is excreted by the kidney. The possibility of renal impairment in the elderly must be considered and the dosage should be adjusted. Adequate hydration of elderly patients taking high oral doses of Acyclovir should be maintained.
Pediatric: Safety and efficacy of oral Acyclovir in children younger than 2 years of age have not been established.
Powder for infusion: The dose and duration of administration depend on the type of virus, severity of the infection and the patient's condition or VILERM IV INFUSION is used as directed by the physician.
A course of treatment with Acyclovir 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 and neonatal herpes simplex infections usually lasts 10 days.
Acyclovir should be administered by IV infusion.
IV infusion: Reconstitution and IV preparation for IV administration: VILERM IV INFUSION (250 mg vial) should be reconstituted using 10 ml of either sterile water for injection or 0.9% sodium chloride injection to provide a solution containing 25 mg Acyclovir per ml.
VILERM IV INFUSION (500 mg vial) should be reconstituted using 20 ml of either sterile water for injection or 0.9% sodium chloride injection to provide a solution containing 25 mg Acyclovir per ml.
VILERM IV INFUSION (500 mg vial) should be reconstituted using 10 ml of either sterile water for injection or 0.9% sodium chloride injection to provide a solution containing 50 mg Acyclovir per ml.
Do not use bacteriostatic water for injection containing benzyl alcohol or parabens for reconstitution.
After that, the reconstituted solutions could be diluted to 50-100 ml of compatible infusion solution such as 0.9% sodium chloride injection, 0.45% sodium chloride injection, 4% dextrose injection and 0.18% sodium chloride injection, 2.5% dextrose injection and 0.45% sodium chloride injection, compound sodium lactate solution (Hartmann's solution) (Infusion concentrations of 7 mg/ml or lower are recommended).
Add the required volume of reconstituted solution to the chosen infusion solution, as recommended, and shake well to ensure adequate mixing occurs.
Acyclovir solution for infusion should be administered by slow intravenous infusion at a constant rate over 60 minutes and may be administered by a controlled-rate infusion pump.
The risk of contamination should be taken into account for IV preparations. Reconstitution and dilution of the Acyclovir solution should be carried out immediately before use and should be under full aseptic conditions. Any unused solution should be discarded.
Reconstituted or diluted solutions should not be refrigerated. Refrigeration of the reconstituted solution may result in formation of a precipitate which will redissolve at room temperature; potency of the drug does not appear to be affected by precipitation and subsequent redissolution.
If Acyclovir sodium is diluted in solutions, the color of solution may be pale yellow. A yellow discoloration may appear and the color of solution depends on the concentration of the solvent. In case the healthcare professional is following the recommendation, this discoloration of the solution does not affect the drug's potency.
Stability after reconstitution: Stability after reconstitution of VILERM IV INFUSION.
VILERM IV INFUSION 250 MG: See Table 3.

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VILERM IV INFUSION 500 MG: See Table 4.

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The Acyclovir solution should be administered by slow intravenous infusion at a constant rate over at least 60 minutes.
Administration in patients with normal renal function: Obese patients should be dosed at the recommended adult dose using ideal body weight, rather than actual body weight. (See Table 5.)

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Administration in acute and chronic renal impairment: Caution is advised when administering Acyclovir intravenous for infusion to patients with impaired renal function. Adequate hydration should be maintained.
The dose and frequency of administration of Acyclovir should be adjusted in patients with impaired renal function, according to the degree of impairment. (See Table 6.)

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Administration in elderly: Elderly patients are likely to have reduced renal function. Therefore, should use with caution in the elderly.

Overdose and treatment: Tablet: There is no specific antidote for Acyclovir.
Acyclovir adult overdosage involving ingestion of up to 20 g of the drug have been reported. Inappropriately high doses and in patients with fluid and electrolyte imbalance result in elevations in BUN and serum creatinine concentration and subsequent renal failure. Acyclovir adult overdosage associated with the development of lethargy, agitation, seizures and coma. 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. 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. At renal concentrations exceeding 2.5 mg/mL, Acyclovir crystals may precipitate in the renal tubules, possibly causing renal dysfunction and eventual renal failure and anuria. If acute renal failure and anuria occur, use of hemodialysis should be considered until renal function is restored. Acyclovir has low protein binding and volumes of distribution, and can be removed by hemodialysis. Data are limited regarding peritoneal dialysis but this method does not appear to appreciably remove the drug.
Powder for infusion: Overdosage, when the drug was administered by rapid intravenous injection or inappropriately high dose, particularly in patients with water and electrolytes imbalance, may cause elevation of serum creatinine and blood urea nitrogen (BUN). At renal concentrations exceeding 2.5 mg/ml, Acyclovir crystal may precipitate in the renal tubules, possibly causing renal failure. Moreover, neurological effects including confusion, hallucinations, agitation, seizures and coma have been described in association with overdosage.
Acyclovir is removed by hemodialysis.

The drug is contraindicated in patients with known hypersensitivity to Acyclovir, valacyclovir or any component of the formulation.

Tablet: Care should be taken to maintain adequate hydration in patients receiving high oral dose of Acyclovir. High doses, dehydration or pre-existing renal impairment increase the risk of Acyclovir-associated acute renal failure.
Acyclovir is excreted by the kidney. The possibility of renal impairment in the elderly must be considered and the dosage should be adjusted. Both the elderly patients and patients with existing renal impairment are at increased risk of developing neurological adverse effects and should be closely monitored for evidence of these adverse effects.
Patients receiving Acyclovir for the treatment of genital herpes should avoid sexual contact while visible lesions are present since there is a risk of infecting their sexual partner. The patient should always use condoms, as the disease can also be transmitted in the absence of symptoms.
Acyclovir should be used with caution in patients receiving other nephrotoxic drugs concurrently since the risk of Acyclovir-induced renal impairment and/or reversible central nervous system (CNS) symptoms is increased in these patients. Adequate hydration should be maintained in patients receiving Acyclovir.
Powder for infusion: Administration of Acyclovir by intravenous infusion should be given slowly at a constant rate over a period more than 60 minutes to avoid precipitation of Acyclovir in the kidney.
Should adjust balances of water and electrolytes in patients with dehydration before administration of this drug.
In case of treatment of genital herpes simplex infections, patients should avoid sexual contact during treatment to prevent further infections.
Use with caution in patients receiving other nephrotoxic drugs concurrently since the risk of Acyclovir - induced renal impairment is increased in these patients.
Sodium is a component of the drug. Therefore, use with caution in patients on a controlled sodium diet.
Use in Children: Tablet: Safety and effectiveness in pediatric patients younger than 2 years have not been established.

Pregnancy: Pregnancy category B.
There are no adequate and well-controlled studies using Acyclovir in pregnant women. The drug should not be administered to pregnant women unless when the potential benefits outweigh the risks to the fetus.
Lactation: Acyclovir is distributed into breast milk and in some instances concentrations are higher than in maternal serum. Caution is advised if Acyclovir is to be administered to a nursing woman. Advise breast-feeding mothers with herpetic lesions near or on the breast to avoid breast-feeding.

Undesirable effects from the use of Acyclovir may occur: Central nervous system (CNS): Aggressive behavior, agitation, ataxia, coma, confusion, decreased consciousness, delirium, dizziness, encephalopathy, hallucinations, obtundation, paresthesia, psychosis, seizures, somnolence, tremor. These symptoms are often found in patients with renal impairment and in older adults.
Gastrointestinal: Nausea, vomiting, diarrhea, gastrointestinal distress.
Hematologic: Anemia, hemolysis, leukocytoclastic vasculitis, leukocytosis, leukopenia, lymphadenopathy, neutrophilia, thrombocytosis, thrombocytopenia.
Dermatologic and hypersensitivity reactions: Rash, pruritus, urticaria, Stevens-Johnson syndrome.
Renal: Increased BUN and/or serum creatinine concentration, renal failure/anuria, hematuria.
Miscellaneous: Fever.
Tablet: Central nervous system (CNS): Dysarthria, headache, malaise.
Hematologic: Thrombotic thrombocytopenic purpura, hemolytic uremia syndrome.
Dermatologic and hypersensitivity reactions: Alopecia, angioedema, anaphylaxis, erythema multiforme, photosensitivity rash, toxic epidermal necrolysis.
Hepatic: Elevated liver function test results, hepatitis, hyperbilirubinemia, jaundice.
Miscellaneous: Pain.
Rare but important or life-threatening: Hypotension, myalgia, peripheral edema, thirst, visual abnormalities.
Powder for infusion: Local effects: When given intravenously it may cause local reaction at the injection site with inflammation, phlebitis and tissue necrosis.
Renal effects: Abnormal urinalysis.
In case of rapid administration, transient increases in BUN and serum creatinine concentrations. Renal failure occurred especially in patients with dehydration or used Acyclovir concomitantly with other nephrotoxic drugs.
GI effects: Anorexia.
Hematological effects: Disseminated intravascular coagulation, hemoglobinemia, neutropenia.
Others: Liver dysfunction, hepatitis, jaundice, hypotension, myalgia, peripheral edema, thirst, visual abnormalities.

Patients should be monitored closely during Acyclovir-zidovudine combination therapy because it may cause neurotoxicity.
Concomitant administration of Acyclovir and antifungal agent (amphotericin B, ketoconazole) have shown synergistic, therefore the greater antiviral activity of Acyclovir.
Concomitant administration of probenecid and Acyclovir has reportedly increased area under the plasma concentration-time curve (AUC) because inhibition of the renal secretion of Acyclovir by probenecid.
Tablet: Concomitant administration of valproic acid and Acyclovir has decreased valproic acid plasma concentrations and potential increased seizure activity.
Powder for infusion: Acyclovir should be used with caution in patients receiving interferon, the drugs have an additive or synergistic antiviral effect.
IV Acyclovir should be used with caution in patients receiving intrathecal methotrexate.
Increases in plasma of Acyclovir and of the inactive metabolite of mycophenolate mofetil, an immunosuppressant agent used in transplant patients, have been shown when the drugs are coadministered.
Care is also required (with monitoring for changes in renal function) if administering intravenous Acyclovir with drugs which affect other aspects of renal physiology (e.g. cyclosporin, tacrolimus).

Store below 30°C.
Powder for infusion: Since no antimicrobial preservative is included in VILERM IV INFUSION preparation, reconstitution and dilution must be carried out under full aseptic conditions before use. Use the reconstituted preparation immediately and any unused solution should be discarded.
Reconstituted or diluted solutions should not be refrigerated.

Antivirals

J05AB01 - aciclovir ; Belongs to the class of nucleosides and nucleotides excluding reverse transcriptase inhibitors. Used in the systemic treatment of viral infections.

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