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Additional information about the drug Aciclovir


Aciclovir ( ACV ), also known as acyclovir, is an antiviral medication.
Common side effects include nausea and diarrhea.
The discovery of aciclovir was announced in 1977.
Contents
1 Medical use
1.1 Pregnancy
2 Adverse effects
2.1 Systemic therapy
2.2 Topical therapy
3 Drug interactions
4 Detection in biological fluids
5 Mechanism of action
5.1 Resistance
5.2 Microbiology
6 Pharmacokinetics
7 History
8 Society and culture
8.1 Names
8.2 Cost
9 Notes
10 References
11 Further reading
12 External links
Medical use
400 mg pills of aciclovir
Aciclovir is used for the treatment of herpes simplex virus and varicella zoster virus infections, including:
Genital herpes simplex (treatment and prevention )
Neonatal herpes simplex
Herpes simplex labialis ( cold sores )
Shingles
Acute chickenpox in immunocompromised patients
Herpes simplex encephalitis
Acute mucocutaneous HSV infections in immunocompromised patients
Herpes of the eye and herpes simplex blepharitis (a chronic (long-term) form of herpes eye infection)
Prevention of herpes viruses in immunocompromised people (such as people undergoing cancer chemotherapy)
Its effectiveness in treating Epstein-Barr virus (EBV) infections is less clear.
Aciclovir taken by mouth does not appear to decrease the risk of pain after shingles.
Intravenous aciclovir is effective to treat severe medical conditions caused by different species of the herpes virus family, including severe localized infections of herpes virus, severe genital herpes, chickenpox and herpetic encephalitis. It is also effective in systemic or traumatic herpes infections, eczema herpeticum and Herpes simplex meningitis.
Reviews of research dating from the 1980s show there is some effect in reducing the number and duration of lesions if aciclovir is applied at an early stage of an outbreak.
Pregnancy
Classified as a Category B Drug,
Aciclovir is recommended by the CDC for treatment of varicella during pregnancy, especially during the second and third trimesters
Aciclovir is excreted in the breast milk, therefore it is recommended that caution should be used in breast-feeding women. It has been shown in limited test studies that the nursing infant is exposed to approximately 0.3 mg/kg/day following oral administration of aciclovir to the mother. If nursing mothers have herpetic lesions near or on the breast, breast-feeding should be avoided.
Adverse effects
Systemic therapy
Common adverse drug reactions (≥1% of patients) associated with systemic aciclovir therapy (oral or IV) include nausea, vomiting, diarrhea, encephalopathy (with IV use only), injection site reactions (with IV use only) and headache. In high doses, hallucinations have been reported. Infrequent adverse effects (0.1–1% of patients) include agitation, vertigo, confusion, dizziness, oedema, arthralgia, sore throat, constipation, abdominal pain, hair loss, rash and weakness. Rare adverse effects (<0.1% of patients) include coma, seizures, neutropenia, leukopenia, crystalluria, anorexia, fatigue, hepatitis, Stevens–Johnson syndrome, toxic epidermal necrolysis, thrombotic thrombocytopenic purpura and anaphylaxis. Intravenous aciclovir may cause reversible nephrotoxicity in up to 5% to 10% of patients because of precipitation of aciclovir crystals in the kidney. Aciclovir crystalline nephropathy is more common when aciclovir is given as a rapid infusion and in patients with dehydration and preexisting renal impairment. Adequate hydration, a slower rate of infusion, and dosing based on renal function may reduce this risk. Topical therapy Aciclovir topical cream is commonly associated (≥1% of patients) with: dry or flaking skin or transient stinging/burning sensations. Infrequent adverse effects include erythema or itch. Drug interactions Ketoconazole : In-vitro replication studies have found a synergistic, dose-dependent antiviral activity against HSV-1 and HSV-2 when given with aciclovir. However, this effect has not been clinically established and more studies need to be done to evaluate the true potential of this synergy. Probenecid : Reports of increased half life of aciclovir, as well as decreased urinary excretion and renal clearance have been shown in studies where probenecid is given simultaneously with aciclovir. Interferon : Synergistic effects when administered with aciclovir and caution should be taken when administering aciclovir to patients receiving IV interferon. Zidovudine : Although administered often with aciclovir in HIV patients, neurotoxicity has been reported in at least one patient who presented with extreme drowsiness and lethargy 30–60 days after receiving IV aciclovir; symptoms resolved when aciclovir was discontinued. Detection in biological fluids Aciclovir may be quantitated in plasma or serum to monitor for drug accumulation in patients with renal dysfunction or to confirm a diagnosis of poisoning in acute overdose victims. Mechanism of action Structures of guanosine and aciclovir compared Aciclovir is converted by viral thymidine kinase to aciclovir monophosphate, which is then converted by host cell kinases to aciclovir triphosphate (ACV-TP). Resistance Resistance to aciclovir is rare in people with healthy immune systems, but is more common (up to 10%) in people with immunodeficiencies on chronic antiviral prophylaxis (transplant recipients, people with acquired immunodeficiency syndrome due to HIV infection). Mechanisms of resistance in HSV include deficient viral thymidine kinase; and mutations to viral thymidine kinase or DNA polymerase, altering substrate sensitivity. Microbiology Varicella zoster virus-produced plaques in monolayers of MRC5 cells. When the virus was reproducing each well contained different amounts of the antiviral drug aciclovir. By counting the plaques (holes formed by the virus in the layer of cells) the potency of the aciclovir to the virus was calculated. Aciclovir is active against most species in the herpesvirus family. In descending order of activity: Herpes simplex virus type I (HSV-1) Herpes simplex virus type II (HSV-2) Varicella zoster virus (VZV) Epstein-Barr virus (EBV) Cytomegalovirus (CMV) – least activity Pharmacokinetics Aciclovir is poorly water-soluble and has poor oral bioavailability (15–30%), hence intravenous administration is necessary if high concentrations are required. When orally administered, peak plasma concentration occurs after 1–2 hours. Aciclovir has a high distribution rate; protein binding is reported to range from 9 to 33%. History Aciclovir was seen as the start of a new era in antiviral therapy, as it is extremely selective and low in cytotoxicity. Vince later went on to invent abacavir, an nRTI drug for HIV patients. Society and culture Names Aciclovir is the INN and BAN while acyclovir is the USAN and former BAN. It was originally marketed as Zovirax; patents expired in the 1990s and since then it is generic and is marketed under many brand names worldwide. Cost The wholesale cost for a 400 mg tablet in March 2016 was between US$0.03 and US$0.12 per dose. Notes ^ Subject to the same conditions as before

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