Interacting drugs- summary

+Famciclovir-

Cimetidine                                                                                                                    peniciclovir AUC and urinary recovery increased in 12 healthy volunteers following a single 500mg famciclovir dose after pretreatment with cimetidine 400mg for 7 days. The magnitude of this effect is considered to be of no clinical importance

Probenecid                                                                                                                           concurrent use with probenecid or other drugs significantly eliminated by active renal tubular secretion may result in increased plasma concentrations of penciclovir

Theophylline-                                                                                                                        renal clearance of penciclovir decreased. The magnitude of this effect is of no clinical importance

Digoxin-                                                                                                                               after a single dose admin of digoxin and famciclovir in 12 healthy males volunteers, Cmax of digoxin increased by 19% as compared to digoxin administered alone

CNS- Headache, dizziness, insomnia, somlolence, paresthesia.

GI- Nausea, diarrhea, abdominal pain,dyspepsia, flatulance, constipation, vomiting, anorexia

Body as a whole- Fatigue, pain, injury, fever, rigors

Respiratory- URI, pharyngitis, sinusitis Musculoskeletal- back pain, arthalgia

Dermatologic- pruritus, zoster/genital hepres- related signs/symptoms/ complications

Hypersensitivity to famciclovir

Special precautions:

Renal function impairment, pregnancy, lactation.

Warnings-

Renal function impairment- dosage adjustment is recommended when administering famciclovir to patients with creatinine values < 60ml/min

Carcinogenesis/mutagenesis/fertility impairment- a significant increase inthe indicidence of mammary adenocarcinoma was seen in female rats receiving 600mg/kg/day

Elderly- the effect of rash resolution was more pronounced in patients > 50 years of age.

Pregnancy- use during pregnancy only if benefit clearly exceeds the potential risk to the fetus.

Lactation- Decide whether to discontune nursing or discontinue the drug taking into account the importance of the drug to the mother.

Children- safety and efficacy in children < 18 years have not been established.

Approved by FDA on June 29, 1994

Herpes zoster

Dosage:

Recommended dose is 500mg every 8 hrs for 7 days. Therapy should be initiated promptly at the first sign or symptom if medical management of genital herpes recurrence is indicated

Overdosage-

No acute overdosage has been reported. Give appropiate symptomatic and supportive therapy. Penciclovir is removed by dialysis.

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.

EVIDENCE- BASED MEDICINE (April 2003)

Genital Herpes

Comparative effectiveness of various interventions

Beneficial

1. Oral antiviral therapy in first episodes

2. Oral antiviral treatment taken at start of a recurrence

3. Daily oral antiviral treatment in people with high rates of recurrence.

Likely to be beneficial

1. Daily oral antiviral treatment in late pregnancy. In women with a hostory of genital herpes.

Unknown effectivess

1. Psychotherapy to reduce recurrence

2. Interventions to prevent sexual transmision

3. Serological screening and counselling in late pregnancy Likely to be ineffective or harmful 1. Abdominal delivery in women with genital lesions at terms.

KEY POINTS

1. Clinical trials have found that oral antiviral treatment reduces the duration of symptoms, lesions, and viral shedding in first and recurrent episodes of general herpes, and that daily treatment reduces the rate of recurrence.

2. Trials have found no significant difference in effectivenes or adverse effects beween acyclovir, valacyclovir and famcyclovir.

3. There is insufficient evidence on the role of interventions to prevent sexual transmission.

4. The highest risk of mother-to-baby transmission is in women newly infected with genital herpes in late pregnancy. There is inadquate evaluation of intervention to prevent infection in late pregnancy (such as serological screening and counselling)

5. It has been found that the effect of abdominal delivery on mother-to-baby transmission had not been adequately evaluated. The procedure has the risk of increased maternal morbidity and mortality.

6. Limited evidence from trials suggests that antiviral treatment may reduce the number of pregnant women with genital lesions at term. Since women with genital lesions are usually offered abdominal deliveries, antiviral treatment may reduce the risk of abdomnal delivery

Pharmacology

Famciclovir undergoes biotransformation to the active antiviral compound penciclovir, which has inhibitory activity against hepes simplex virus

Pharmacokinetics:

The absolute bioavilability is 77%. Following the oral administration of a single 500mg dose of radioactive famciclovir ,73% and 27% of administered radioactivity were recovered in urine and feces.

May be taken without regard to meals

Pregnancy:

Use only, if required

Lactation:

Use with caution.

Children:

Safety and efficacy in children below 18 yrs have not been established.