Interacting drugs- summary

+ Acyclovir

Probenecid

Acyclovir bioavilability and terminal plasma half-life increased, and renal clearance decreased

Zidovudine

Severe drowsiness and lethargy occur with cuncurrent use

Treatment of Herpes

ACYCLOVIR- (Acycloguanosine)    Antiviral agent

ZOVIRAX (BIOVALLLI)       -    Ointment 5%(50mg/g )   in apolyethylene base in                                                                  15g tubes

                                                 Cream 5% (Mg/g)       Cetostreryl alcohol, mineral oil, in                                                an aqueous cream base in 2 2g tubes

GI-  Nausea, vomitting, headache, diarrhoea.

CNS- Headache, dizziness, fatigue.

Dermatologic- skin rash

Other- anorexia, edema, inguinal adenopathgy, leg pain, medication taste, sore throat Haematological changes (occasional).

Burning or erythema (topical use).

Eye appln may produce stinging and superficial punctate keratopathy.

I.V. appln: local reaction at injection site, inflammation pain, phlebitis. May lead to extra-vasitation & ulceration. Increase in blood urea & creatinine.

Some cases of renal impairment & even acute failure.

Occasional increased value for liver enzymes.

Haematological & encephalogical changes.

Known hypersensitive.

Special precautions:

Severe renal impairment, pregnancy. Maintain adequate hydration.

Diagnosis- proof of HSV infectin rests on viral isolation and identification in tissue culture. Genital herpes- avoid sexual intercourse when visible lesions are present because of risk of infecting intimate partners.

Herpes zoster infections- adults > 50 years of age have more severe shingles and acyclovir treatment showed more benefits for older patients.

Chicken pox- although chickenpox in otherwise healthy chidren is usually a self-limited disease of mild to moderate severity, adolenscents and adults tend to have more severe disease.

Do not exceed the the recommended dosage , frequency, or length of treatment. Base dosage adjustments on estimated creatinine claerance.

Renal effects- precipitation of acyclovir crystals in renal tubules can occur if the maximum sloubility of free acyclovir (2.5mg/ml at 37C in water) is exceeded or if the drug is administred by bolus injection.

Hydration- accompany IV infusion by adequate hydration. Since maximum urine concentration occurs within the first 2 hours following infusion, establish sufficient urine flow during that period to prevent precipitation in renal tubules.

Resistence- exposure to HSV isolates to acyclovir in vitro can lead to the emergence of less sensitive viruses. In severly immunocompromised patients prolonged or repeated courses of acyclovir may result in resistent viruses which may not fully respond to acyclovir therapy.

Warnings-

Testicular atropy- occured in rats administerd intraperitoneally at 320 or 80 mg/kg/day for 1 to 6 months, respy, Some recovery of sperm was evident 30 days post-date.

Pregnancy- Use during pregnancy only if the potential benefits outweigh the potential risks to the fetus.

Lactation- excercise caution when administering to a nursing woman.

Children- safety and efficacy of oral acyclovir in children< 2 years of age have not been established.

Indications:

Parentral- Treatment of initial and recurrent mucosal and cutaneous HSV-1 and HSV-2 and Varicella-Zoster (shingles) Oral - recurrent episodes of genital herpes in certain patients. Acute treatment of Herpes Zoster (Shingles) and chicken pox.

Dosage:

May be taken with meals to reduce GI discomfort 

200mg every 4 hours 5 times daily for 10 days. Chronic supressive therapy for recurrent disease- 400mg 2 times daily upto 12 months, to be followed by re-evalution.

Stability and storage: Use reconstituted solution within 12 hours, once diluted. For administration, use each dose within 24 hours.

Overdosage- Symptoms Precipitation of acyclovir inrenal tibules may occur when the solubility (2.5mg/ml) in the intratubular fluid is exeeded,

Parentral -overdosage has occured in bolus injections or inappropiately high doses and in patients whose fluid and electrolyte balance was not properly monitored. Elevation in BUN, serum creatinine and subsequent renal faliure resulted.

Oral- doses as high as 800mg 6 times daily for 5 days have been administered without acute untoward effects.

Treatment

1. Acyclovir is dialyzable. A 6 hour hemodialysis results in 60% decrease in plasm acyclovir concentration.

2. Peritonal dialysis apears less efficient in removing acyclovir from the blood.

3.In the event of acute renal failure and anuria, the patient may benefit from hemodialysis until renal function is restored

Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

For Availability/supplies 

EVIDENCE BASED MEDICINE (MIMS April 2003)

Post-herpetic Neuralgia

Comparitive effectiveness of various interventions

Prevention of post-herpetic neuralgia

Beneficial

1. Oral antiviral agents such as acyclovir, famciclovir, valaciclovir, netivudine

2. Tricyclic antidepressants (amitriptyline)

Unknown effectiveness

1. Levodopa

2. Amantadine

3. Isoprinosine

4. Adenosine monophosphate

Unlikely to be beneficial

1. Topical antiviral agents (idoxurine) for relief of acute oain only

2. Cimetidine

Ineffective or harmful

1. Corticosteroids

Relieving established post-herpetic neuralgia Beneficial

1. Tricyclic antidepressants (amitriptyline)

2. Oxycodone (opiod)

3. Gabapentin (anticonvulasant)

Unknown effectiveness

1. Capsaicin (topical counterirritant)

2. Topical lignocaine

Ineffective or harmful

1. Epidural morphine

2. Dextromethorphan

KEY POINTS

1. Daily acyclovir reduced the relative risk of of post-herpetic pain at six months by about 50 % compared with placebo

2. Famciclovir significantly reduced pain duration after acute herpes zoster.

3. Idoxuridine was associated with short term pain relief in acute herpes zoster but did not prevent post-herpetic neuralgia

4. Conflicting evidence on whether corticosteroids alone prevent post-herpetic neuralgia. Limited evidence that high dose steroids and antiviral agents combined may speed healing of acute zoster. No evidence that it reduces post-herpetic neuralgia

5. Amitriptyline started during the acute episode reduced prevalence of post-herpetic neuralgia at six months.

6. Insufficient evidence on the effect of other drug tretment.

Acyclovir

1. Avoid sexual intercourse when visible herpes lesions are present

2. Oral Acyclovir does not eliminate latent HSV virus and is not a cure.

3. Do not exceed the recommended dosage, do not share medication with others.

4. Notify physician if frequency and severity of recurrences do not improve. 5.Allergies- tell your doctor if you have ever had any unusual or allergic reaction to acyclovir or ganciclovir

5.Pregnancy - use to be avoided

6.Breast feeding-breast feeding should be stopped during treatment.

7 Children - Safety and efficacy in children below 2 years have not been established.

8.Elderly- Acyclovir has been used in elderly and has not been shown to different side effects than in younger adults.

9. Other medicines - Certain other medicines should not be used together at all. Let your doctor know what other medicines you are taking, so that he can advice you accordingly. If you are receiving actclovir by injection, it is especially important that your doctor know that you are taking any of the following- Carmusatine, Cisplatin, combination of medicines containg acetaminophen and aspirin or other salicylates .Use of these medicines may increase side effects

10. Other medical problems - Tell your doctor if you have any other medical problems especially - Kidney disease or Nerve disease- -acyclovir by injection may increae the chance of nervous system side effects

11. Dose - The dose of acyclovir will be different for different patients. Follow your doctors order.

12. Missed dose - If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.

13. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.

14. Outdated medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.

15. Interaction with food - Absorption is unaffected by food. May be taken with meals

Pharmacology:

A synthetic acyclic purine nucleoside analog, acyclovir has in vitro inhibitory activity against Herpes simplex type 1 and 2.

Pharmacokinetics:

Acyclovir is widely distributed in tissues and body fluids, including brain and kidney, lung ,liver, muscle spleen, uterus, vaginal mucosa. Oral Acyclovir is slowly and incompletely absorbed from the GI tract .Peak concentrations are reached in 1.5 to 2 hours, absorption is unaffected by food.

May be taken with meals to reduce GI discomfort 

Absorption is unaffected by food. May be taken with meals

Pregnancy:

Use in pregnancy only if potential benefits outweigh potential risks.

Lactation:

Excercise caution while administrering to nursing women.

Children:

Safety and efficacy in children below 2 years have not been established.