Aciclovir Powder for Infusion 250mg
ABOUT YOUR MEDICINE
Under what local brands and in what dosages is generic Acyclovir or Aciclovir sold in pharmacies of Britain, United States, and Canada?
In pharmacies of the United States, Great Britain and Canada the pharmacists offer you to buy Aciclovir (UK) or Acyclovir (US, Canada) (according to your prescription or without a prescription) under such brand names and in such strengths and dosage forms:
| UK | US | Canada |
| Aciclovir 5% w/w Cream
Aciclovir Tablets 200, 400, 800mg Aciclovir 200mg/5ml & 400mg/5ml Oral Suspension Zovirax 200mg Tablets Zovirax 800mg Tablets Zovirax Cream Zovirax Eye Ointment Zovirax IV 250mg, 500mg Zovirax Suspension |
Acyclovir 200mg Capsuls
Acyclovir 400mg Tablets Acyclovir 800mg Tablets Zovirax 400mg Tablets Zovirax 800mg Tablets Zovirax 5% Eye Ointment Zovirax 5% Cream |
Acyclovir 200mg Tablets
Acyclovir 400mg Tablets Acyclovir 800mg Tablets Mylan-Acyclovir 200, 400, and 800mg Tablets Zovirax 200mg Tablets Zovirax 400mg Tablets Zovirax 5% Eye Ointment Zovirax 5% Cream |
Aciclovir is an anti-viral drug and it is active against the viral infections described under ‘USES’ below. Aciclovir Powder for Infusion 250mg may be used against certain viral infections as follows:
- Treatment and prevention of Herpes simplex virus (HSV) infections in patient who have a reduced immune response (weakened resistance) to infection.
- Treatment of infection of the brain caused by Herpes simplex virus (HSV)
- Treatment of infections due to Varicella zoster virus (shingles and chickenpox)
- Treatment of Herpes simplex virus infections in the newborn and in the infants up to 3 months of age.
BEFORE TAKING YOUR MEDICINE
Before you receive this medicine, tell your doctor if
- you are allergic to aciclovir or valaciclovir
- you are pregnant or think you may be pregnant, or if you are breast feeding
- you are suffering from a disease of the kidneys
- you are taking any other medicines, including probencid (for gout or for use in combination with an antibiotic), cimeditine (to reduce the amount of acid in your stomach), mycophenolate mofetil, cyclosporin or tacrolimus (drugs used to reduce the body’s immune response).
HOW YOUR MEDICINE IS GIVEN
Before use, the powder in the vial must be dissolved in Water for Injections. The resultant solution, which may be further diluted, is administered slowly into a vein. Treatment with this medication is usually over a 5 day period, depending on your condition and how you respond to the treatment. For infection of the brain caused by Herpes simplex virus (HSV) or for HSV infection in the newborn, the treatment period is usually 10 days. When used to prevent an infection, the length of treatment will depend on the risk period. Dosage recommendations are as follows:
Adults: The recommended dosage for Herpes simplex infections (excluding herpes infection of the brain) or Varicella zoster infections is 5mg per kg bodyweight every 8 hours, provided that the kidneys are functioning normally. In patients who have a reduced immune response against infection, the recommended dosage for herpes infection of the brain or Varicella zoster infections is 10 mg per kg bodyweight every 8 hours, provided that kidneys are functioning normally. Children: The recommended dosage for Herpes simplex infections (excluding herpes infection of the brain) or Varicella zoster infections is 250mg per square metre of body surface area every 8 hours. In patients who have a reduced immune response against infection, the recommended dosage for herpes infection of the brain or Varicella zoster infections is 500mg per square metre of body surface area every 8 hours, provided that the kidneys are functioning normally.
AFTER YOU RECEIVE YOUR MEDICINE
As well as having beneficial effects, a medicine may sometimes cause unwanted effects in some patients. If you notice any one of the following effects, tell your doctor:
- Nausea or vomiting
- Feeling weak or light-headed, bruising of the skin, fever, chills, or signs of an infection
- A skin rash or wheal, increased sensitivity of the skin to sunlight, itching
- Breathlessness, swelling of the face or mouth, feeling very weak and unwell
- Pain or inflammation around the site of injection
- Any problems with your kidneys, for example passing too little or too much urine
- Yellowing of the skin or the white of the eyes
- Confusion, hallucination, feeling agitated or shaky, drowsiness, mood changes or convulsions
You should tell your doctor is your experience any unwanted effects that are not listed here. In children who have kidney damage, the doctor may decide to reduce the dosage of Aciclovir. Newborn babies and infants up to age 3 months: The recommended dosage for treatment of Herpes simplex infections is 10 mg per kg bodyweight every 8 hours. For Herpes simplex infections in the newborn, the usual treatment period is 10 days. Elderly patients: If you are elderly, your doctor may decide to reduce the dosage of Aciclovir depending on your ability to clear the drug through the kidneys. Patients with kidney damage: If you have a problem with your kidneys, your doctor will reduce the dosage of Aciclovir in maintenance with your particular requirements.
WHAT TO DO IN CASE OF AN OVERDOSE OR A MISSED DOSE
If you think that you may have been given too much of this medicine, or that you may have missed a dose, tell your doctor.
STORING THIS MEDICINE
Do not use this product after the expiry date printed on the vial or carton. Do not store above 25 C. Store the vials in original packaging. After reconstitution use immediately. Discard any unused portion.
Side Effects
Acyclovir is an acyclic purine nucleoside. Its antiviral activity depends upon intracellular phosphorylation to its triphosphate derivative. Because of its higher affinity for viral thymidine kinase, Acyclovir is phosphorylated at a much higher rate by the viral enzyme. Thus, it is almost exclusively active in infected cells, fulfilling one of the selectivity principles of antiviral drugs. In addition, Acyclovir triphosphate serves as a better substrate for viral than for host cell DNA polymerase and thereby causes preferential termination of viral DNA synthesis.
Acyclovir is active against Herpes simplex virus type 1 (HSV-1), HSV-2, Varicella zoster virus (VZV), Herpesvirus simiae, and to a lesser degree Epstein-Barr virus (EBV). Resistant strains of HSV can arise owing to the emergence of thymidine kinase-deficient mutants. Other forms of resistance patterns are less common.
Acyclovir is used topically or systemically, orally or intravenously. Its therapeutic potential is most impressive in active parenchymal or systemic HSV infections. The latency stage of the viral infection is not affected. Since the blood-brain barrier is well penetrated, aciclovir is the treatment of choice for HSV encephalitis.
Very few adverse effects, generally of minor importance, have been reported. In immunosuppressed patients abnormal liver function, encephalopathy, and myelosuppression have been observed; however, it is unclear at present whether these adverse effects are related to the drug itself or to the underlying disorder.
Comparative studies
The effects of Acyclovir and valaciclovir for anogenital herpes have been studied in HIV-infected individuals in two controlled trials. In the first study, 1062 patients with CD4+ counts over 100 x 106/1 received valaciclovir or aciclovir for 1 year and were assessed monthly. In the second study, 467 patients were treated episodically for at least 5 days with valaciclovir or Acyclovir and were assessed daily. Valacyclovir was as effective as aciclovir for suppression and episodic treatment of herpesvirus infections. Hazard ratios for the time to recurrence with valaciclovir 500 mg bd and 1000 mg od compared with Acyclovir were 0.73 (95% CI = 0.50) and 1.31 (0.94). Valaciclovir 1000 mg bd and aciclovir had similar effects on the duration of infective episodes (HR — 0.92; CI = 0.75). The most common adverse events, which occurred at similar rates with all regimens, were diarrhea, headache, infections, rashes, nausea, rhinitis, pharyngitis, abdominal pain, fever, depression, and cough.
Acyclovir: Organs and Systems
Neurotoxicity secondary to aciclovir is rare and is associated with high plasma concentrations, such as result from impaired renal function. Although the risk is greatest with intravenous administration, neurotoxicity has previously been noted with oral use.
Symptoms of neurotoxicity, which usually appear within the first 24-72 hours of administration, include tremor, myoclonus, confusion, lethargy, agitation, hallucinations, dysarthria, asterixis, ataxia, hemiparesthesia, and seizures. While aciclovir-induced neurotoxicity is most prevalent with intravenous administration, it has also been reported after oral use in patients with terminal renal insufficiency on hemodialysis.
Neurotoxicity possibly secondary to the topical use of aciclovir has also been described.
A 59-year-old woman on hemodialysis was treated with oral aciclovir 200 mg/day for ophthalmic Herpes zoster. After a few days, an ophthalmic aciclovir cream was started (one application every 6 hours) because of ipsi-lateral Herpes keratitis. After 1 week of combined oral and topical treatment, she became confused, with dysarthria and audiovisual hallucinations. Aciclovir was withdrawn and hemodialysis was initiated. Complete resolution of symptoms was achieved after three hemodialysis sessions in 3 days. Aciclovir plasma concentrations before hemodialysis were high (45 µmol/l) and fell rapidly during hemodialysis.
There is no conclusive evidence for the contribution of the topically administered aciclovir to the high plasma concentrations and subsequent neurotoxicity in this case. However, the authors argued that the existence of high aciclovir plasma concentrations, in spite of careful adjustment of the oral dosage, pointed to significant topical absorption of the drug, especially since the absorption of aciclovir through the skin and mucous membranes may be unpredictable. Coma has been attributed to oral aciclovir.
A 73-year-old man with acute respiratory failure, presumed to be secondary to amiodarone toxicity, developed sepsis and acute renal insufficiency, and required intermittent hemodialysis. Following a Herpes simplex labialis infection he was treated with oral aciclovir (400 mg tds). The next day he became sleepy, disoriented, and agitated. Over the next 48 hours his neurological condition deteriorated and he responded to pain only, had uncoordinated eye movements, tremors, facial and jaw myoclonus, increased reflexes, and hypertonia. After 7 days of aciclovir he became unresponsive and comatose. Aciclovir was withdrawn and hemodialysis carried out more frequently. His neurological status improved over a period of 4 days. Trough plasma concentrations of aciclovir were well above the upper limit of the usual target range.
This appears to be the first case of coma attributable to oral aciclovir. The fact that the patient was receiving oral rather than intravenous aciclovir and was on regular hemodialysis made neurotoxicity unlikely, and this emphasizes the need to be wary of this potentially serious complication in seriously ill elderly patients.
Sensory systems
Local application of 3% ophthalmic ointment can cause mild transient stinging. Diffuse, superficial, punctate, non-progressive keratopathy can develop. This quickly resolves after withdrawal.
Psychological, psychiatric
One report described reversible psychiatric adverse effects in three dialysis patients receiving intravenous aciclovir (8-10 mg/kg/day).
Hematologic
Neutropenia and thrombocytopenia occurred in an 8-year-old boy who was treated with aciclovir 200 mg bd for 5 months for “chronic cold sores”. After withdrawal of aciclovir, the absolute neutrophil and platelet counts normalized within days. There was no recurrence of oral herpes lesions during the ensuing month.
Urinary tract
Renal impairment has been associated with the use of intravenous aciclovir. Transient increases in serum crea-tinine and urea have been observed in 14% of patients treated with bolus injections. These are related to crystal formation in the lower renal tubules when the solubility of aciclovir in urine is exceeded. Slow (1-hour) intravenous infusion and adequate hydration are therefore mandatory. Bolus doses are to be avoided. Dosage modifications for patients with renal insufficiency are based on creatinine clearance.
Crystalluria due to aciclovir occurred within 24 hours of the start of therapy with 500 mg 8-hourly in a 4-year-old African-American boy. Slow intravenous infusion over 1-2 hours and volume repletion avoids the problem.
Renal toxicity has not been described in infants treated with intravenous aciclovir, 5-10 mg/kg every 8 hours for 5-10 days or in children receiving aciclovir 500 mg/m2 intravenously or orally.
Skin
Skin reactions to aciclovir are mostly mild and transitory, including pruritus, pain, rashes, contact dermatitis, and photoallergic contact dermatitis. However, serious reactions occasionally occur. Antiviral drugs that have been implicated include topical aciclovir, cidofovir, idoxuridine, imiquimod, lamivudine, penciclovir, podophyllin, podophyllotoxin, trifluridine, tromantadine, vidarabine, intralesional and ophthalmic solutions of interferon, intravi-treal injections of fomivirsen and foscarnet, and intraocular implants of ganciclovir. Patch-testing in these cases only rarely caused positive reactions to the antiviral drug.
A case of possible aciclovir-induced Stevens-Johnson syndrome has been reported in an HIV-positive patient with mycobacterial disease. However, Stevens-Johnson syndrome is associated with Herpes simplex infection and can be prevented by aciclovir.
Immunologic
Although allergy to aciclovir is unusual, it can occur; in one case it resulted in a skin rash.
A 38-year-old woman of African descent, with a history of atopy and mild asthma, developed a periumbilical, erythematous, maculopapular rash and generalized pruritus after starting aciclovir. The reaction resolved within a few days after withdrawal, recurred when famciclovir was used, and again resolved when famci-clovir was withdrawn. She was successfully stabilized on suppressive therapy after a graded challenge with aciclovir four times a day for 5 days.
Cross-reactivity between aciclovir and famciclovir is unusual. Aciclovir desensitization may be a novel method of treating patients with aciclovir allergy.
Contact sensitization to aciclovir is rare, but frequent application to inflamed skin in relapsing Herpes simplex may increase the risk of allergy. Severe contact dermatitis in a teenager has been reported.
A 16-year-old girl with an 11-year history of frequent cold sores developed an erythematous rash and severe contact dermatitis during oral and topical aciclovir therapy. Patch tests showed contact sensitization to aciclovir and to the related compound ganciclovir.
In a 44-year-old woman who used topical aciclovir for genital herpes, aciclovir contact allergy was associated with a systemic contact allergic reaction with an erythematous vesiculobullous eruption in the labial and perioral skin and a rash on the upper trunk and extremities. Patch tests were positive to aciclovir, valaciclovir, and ganciclovir, but not to famciclovir.
Pre-existing vesicular edematous cheilitis (probably due to contact allergy to the protecting lip salve) was aggravated after application of Zovirax cream. Patch tests to the lip salve were positive, but in addition there were positive photopatch tests to Zovirax cream, but not to its separate constituents.
Second-Generation Effects
Pregnancy
Animal data suggest that Acyclovir is probably safe in pregnancy. There are no reports of teratogenicity in humans, and a report of 312 pregnant women exposed to Acyclovir showed no increase in the number of birth defects compared with the numbers expected in the general population. However, data from larger numbers of human pregnancies are not available to draw reliable conclusions about the safety of Acyclovir in pregnancy.
Drug Administration
Drug administration route
Local necrosis and inflammation can occur due to extravasation of the drug at the site of injection.
Various local adverse effects of Acyclovir eye-drops have been reported, including pruritus, burning sensations, and irritative or allergic conjunctivitis. Persistent superficial punctate keratitis, delayed epithelial healing, and epithelial dysplasia can develop.