Covir 800

Biconvex, oval shape, blue tablet. One side has incision. Another side has the figure "800".
Each tablet contains Aciclovir 800 mg.

Pharmacology: Pharmacodynamics: Aciclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against herpes simplex virus type 1 (HSV-1), 2 (HSV-2), and Varicella Zoster Virus (VZV). In cell culture, aciclovir's highest antiviral activity is against HSV-1, followed in decreasing order of potency against HSV-2 and VZV.
The inhibitory activity of aciclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts aciclovir into aciclovir monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. In accomplished in 3 ways: competitive inhibition of viral DNA polymerase; incorporation into and termination of the growing viral DNA chain; and inactivation of the viral DNA polymerase. The greater antiviral activity of aciclovir against HSV compared with VZV is due to its more efficient phosphorylation by the viral TK.
Pharmacokinetics: Absorption: Absorption of aciclovir from the GI tract is variable and incomplete. It is estimate that 10-30% of an oral dose of the drug is absorbed. Some data suggest that GI absorption of aciclovir maybe saturable; in a crossover study in which aciclovir was administered orally to healthy adults as 200-mg capsules, 400-mg tablets, or 800-mg tablets 6 times daily, the extent of absorption decreased with increasing dose, resulting in bioavailabilities of 20, 15, or 10%, respectively. It is stated that this decrease in bioavailability appears to be a function of increasing dose, not differences in dosage forms. In addition, steady-state peak and through plasma aciclovir concentrations were not dose proportional over the oral dosing range of 200-800 mg 6 times daily, averaging 0.83 and 0.46, 1.21 and 0.63, or 1.61 and 0.83 mcg/mL for the 200-, 400-, or 800-mg dosing regimens, respectively. Peak plasma concentrations of aciclovir usually occur within 1.5-2.5 hours after oral administration. Food does not appear to affect absorption of aciclovir.
Distribution: Aciclovir is widely distributed into body tissues and fluids including the brain, kidney, saliva, lung, liver, muscle, spleen, uterus, vaginal mucosa and secretion, CSF, and herpetic vesicular fluid.
The apparent volume of distribution of aciclovir: Adults: 32.4-61.8 L/1.73 m².
Children 7-12 years: 51.2-53.6 L/1.73 m².
Children 2-7 years: 42 L/1.73 m².
Children 1-2 years: 31.6 L/1.73 m².
Neonates up to 3 months of age: 28.8 L/1.73 m².
Aciclovir is approximately 9-33% bound to plasma proteins at plasma concentration of 0.41-5.2 mcg/mL.
Elimination: Plasma concentrations of aciclovir appear to decline in a biphasic manner. In adults with normal renal function, the half-life of aciclovir in the initial phase averages 0.34 hours and the half-life in the terminal phase averages 2.1-3.5 hours. In adults with renal impairment, both phases may be prolonged, depending on the degree of renal impairment. Aciclovir is excreted principally in urine via glomerular filtration and tubular secretion. The only known urinary metabolite is 9-carboxymethoxymethylguanine. Aciclovir is removed by hemodialysis.

Aciclovir 800 mg tablets are indicated for: the treatment of Herpes simplex virus infections of the skin and mucous membranes including initial and recurrent genital herpes; the suppression (prevention of recurrences) of recurrent Herpes simplex infections in immune-competent patients; the prophylaxis of Herpes simplex infections in immune-compromised patients; the treatment of Varicella infections (chickenpox) and Herpes zoster (shingles). Studies have shown that early treatment of shingles with aciclovir has beneficial effect on pain and can reduce the incidence of post-herpetic neuralgia (zoster-associated pain); 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 aciclovir given conjunction with antiretroviral therapy (mainly oral Zidovudine) reduced mortality in patients with advanced HIV disease and that oral aciclovir preceded by one month's treatment with intravenous aciclovir reduced mortality in bone marrow transplant recipients. In addition oral aciclovir provided effective prophylaxis for herpes virus disease.

Recommended Dose: Adult: Treatment of Herpes simplex: For treatment of Herpes simplex infections, 200 mg aciclovir should be taken 5 times daily at approximately four-hourly intervals omitting the night time dose. Treatment should continue for 5 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 aciclovir should be taken four times daily at approximately six-hourly intervals.
Many patients may be conveniently managed on a regimen of 400 mg aciclovir taken twice daily at approximately twelve-hourly intervals.
Dosage titration down to 200 mg aciclovir 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 aciclovir.
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 aciclovir 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 aciclovir 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.
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 aciclovir 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 (see acyclovir 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 infection in children: 6 years and over: 800 mg aciclovir 4 times daily.
2-<6 years: 400 mg aciclovir 4 times daily.
Under 2 years: 200 mg aciclovir 4 times daily.
Dosing may be more accurately calculated as 20 mg acyclovir/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. Limit 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.
Adequate hydration of elderly patients taking high oral doses of aciclovir should be maintained.
Renal impairment: Caution is advised when administering aciclovir oral formulations to patients with impaired renal function.
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 aciclovir 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).
Mode of Administration: Aciclovir is administered orally. Swallow pill whole. Do not split pills. Food does not appear to affect oral absorption of aciclovir, and drug may be administered without regard to meals.

Overdose and Treatment: Aciclovir overdosage involves ingesting up to 20 g of the drug. Overdosage of IV acyclovir has been reported following administration of rapid IV injections or inappropriately high doses and in patients with fluid and electrolyte imbalance, resulting in elevations in BUN and serum creatinine concentration and subsequent renal failure. Other adverse effects reported with aciclovir overdosage include agitation, coma, lethargy, and seizures. At renal concentrations exceeding 2.5 mg/mL, aciclovir 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.

Aciclovir is indicated in patients known to be hypersensitivity to aciclovir or valaciclovir.

Patients receiving acyclovir for the treatment of genital herpes should be advised that aciclovir is not a cure for genital herpes because genital herpes is a sexually transmitted disease, they should avoid sexual contact while visible lesions are present since there is a risk of infecting their sexual partner.
Patients should be instructed to consult their clinician if severe or troublesome adverse effects occur during aciclovir therapy.
The recommended dosage and duration of aciclovir therapy should not be exceeded. The dose and dosage interval should be carefully adjusted in patients with renal failure or in patients undergoing hemodialysis to prevent drug accumulation, decrease the risk of toxicity, and maintain adequate plasma concentrations of aciclovir. Dosage adjustment should be based on estimated creatinine clearance.
Patients receiving other nephrotoxic drugs concurrently should be used aciclovir with caution since the risk of aciclovir-induced renal impairment and/or reversible CNS symptoms is increased. Adequate hydration should be maintained, however in patients with encephalitis, the recommended hydration should be balanced by the risk of cerebral edema.
Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, which has resulted in death, has occurred in immunocompromised patients receiving acyclovir therapy.
Use in Pregnancy & Lactation: Female patients should be instructed to consult their physician if they become pregnant or intend to become pregnant or if they intend to breast-feed.
Use in Children: The safety and efficacy in children younger than 2 years of age have not been established.
Use in the Elderly: The duration of pain after healing was longer in those 65 years of age and older and nausea, vomiting, and dizziness were reported more frequently in geriatric patients. Geriatric patients are more likely than younger adults to have adverse CNS effects (e.g., coma, confusion, hallucinations, somnolence) during therapy. Geriatric patients also are more likely to have adverse renal effects during therapy and to have reduced renal function requiring dosage adjustment. Aciclovir dosage should be carefully selected for this age group and it may be useful to monitor renal function.

Pregnancy: Category B.
There are no adequate and controlled studies to date using acyclovir in pregnant woman, and the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.
Lactation: Aciclovir is excreted breast milk. Limited data suggest exposure to the breast-feeding infant of approximately 0.3 mg/kg/day following oral administration of aciclovir to the mother. Aciclovir should be administered to nursing women with caution and only when indicated.

Central nervous system: Aggressive behavior, agitation, ataxia, coma, confusion, decreased consciousness, delirium, dizziness, dysarthria, encephalopathy, hallucinations, obtundation, paresthesia, psychosis, seizures, somnolence, tremors. These effects may be marked and particularly in older adults or patients with renal impairment.
Dermatologic: Alopecia, erythema multiforme, photosensitivity rash, pruritus, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis and urticaria.
Gastrointestinal: Diarrhea, gastrointestinal distress and nausea.
Genitourinary: Renal failure, elevated blood urea nitrogen, elevate creatinine, hematuria.
Hematologic/Lymphatic: Anemia, leukocytoclastic vasculitis, leukopenia, lymphadenopathy and thrombocytopenia.
Hepatic: Elevated liver function tests, hepatitis, hyperbilirubinemia and jaundice.
Musculoskeletal: Myalgia.
Special senses: Visual abnormalities.
Miscellaneous: Anaphylaxis, fever, angioedema, headache, pain and peripheral edema.

Concomitant administration of probenecid and aciclovir has reportedly increased the mean plasma half-life and area under the plasma concentration-time curve (AUC) and decreased urinary excretion and renal clearance of acyclovir.
Concomitant use of aciclovir and foscarnet may enhance the nephrotoxic effect of aciclovir.
Concomitant administration of aciclovir and varicella virus vaccine may diminish the therapeutic effect of varicella virus vaccine.
Concomitant use of aciclovir and zidovudine may enhance the CNS depressant effect of zidovudine.

Store below 30°C.

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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