Interacting drugs- summary

Ganciclovir +

Cytotoxic drugs-                                                                                                         cytotoxic drugs inhibit replication of cells . Therefore,consider concomitant use of dapsone, pentamidine, flucytosine, vincristine, vinblastine, adriamysin, amphotericin B, trimethoprim, sulphamethoxazole combinations, only if potential benefits outweigh the risks 

Ganciclovir-+ Didanosine-                                                                                                        steady state didanosine AUC increased when didanosine Didanosine was administered either 2 hrs prior or simulataneously with Ganciclovir. A decrease in steady state ganciclovir was observed

Didanosine+ Ganciclovir-                                                                                               when didanosine was administerd 2 hrs prior to admin of ganciclovir Ganciclovir 

Ganciclovir +Zidovudine -                                                                                               mean steady state ganciclovir AUC decreased in presence of  zidovudine. Steady-state zidovudine AUC increased in the presence of ganciclovir   

+ Ganciclovir-

Imipenem-cilastatin                                                                                                         generalised seizure occured in patients who received ganciclovir and imipenem -clistatin. Do not use these drugs concomittantly. 

Nephrotoxic drugs                                                                                                          increases in serum creatinine were observed following concurrent use of ganciclovir and either cyclosporine or amphotericin B 

Probenecid                                                                                                              gangciclovir AUC increased in the presence of probenecid. Renal clearance of ganciclovir decreased.

Body as a whole-

Fever 38% Abdominal pain 17% Infection 9% Chills 7% Sepsis 4% GI - Diarrhea 41% Nausea 26% Anorexia 15% Vomiting 13% Flatulence 6%

Hemic/Lymphatic-

Leucopenia 29% Anemia 19% Thrombocytopenia 6% CNS - Neuropathy 8% Parasthesia 6% Others- Rash 15% Sweating 11% Pruritus 6% Vitrous disoder 6% Pneumonia 6%

Hypersens to the drug Special precautions:

Monitoring blood counts and platelet count. Large dose and rapid infusion. Phlebitis/pain at site of injection. Hydration.

Photosensitivity Monitoring-

It is recommended that complete blood counts be performed frequently,especially in patients in whom ganciclovir or other gancoclovir or other nucleoside analogs have previously resulted in leukopenia,or in whom neutrophil dosing counts are < 1000 mm3 at the beginning of the treatment.

Large doses/rapid infusion-

larger doses have resulted in increased toxicity. It is likely that more rapid infusions would result in increased toxicity

. Phelbitis/pain at injection site- take care to infuse solutions containing ganciclovir only into veins with adequate blood flow to permit rapid dilution.

Hydration- since ganciclovir is excreted by the kidneys and normal clearance depends on adequate renal function, administration of ganciclovir should be acompanied by adequate hydration.

Photosentivity-

photosentization may occur. Therefore advice patients to take measures against exposure to ultraviolet or sunlight (eg sunscreens, protective clothing) until tolerance is determined.

Warnings-

CMV disease- safety and efficacy has not been established for congenital or neonatal CMV disease treatment of established CMV disease, other than retinitis or use or non-immunocompromised individuals.

Diagnosis of CMV retinitis-

is opthalmologic and should be made by indirect opthalmoscopy. Retinal detachment- has been observed in subjects with CMV retinitis, both before and after initiation of therapy with gancoclovir. Its relationship to therapy is unknown. Hematologic- do not administer if the neutrophil count is < 500/mm2 or platelet count is < 25000/mm3. Granulocytopenia (neutropenia) anemia, and thrombocytopenia have been observed in patients with ganciclovir.

Renal function impairment-

use ganciclovir with caution because the half-life and plasma/serum concentrations of ganciclovir will be increased because of reduced renal clearance.

Elderly-

Pay particular attention to assessing renal function before and during administration of ganciclovir. Pregnancy- Use during pregnancy only if the potential benefits justify the potential risk to trhe fetus. Lactation- Instruct mothers to discontinue nursing if they are receiving ganciclovir. Children- safety and efficacy have not been established. The use of gancoclovir in children warrants extreme caution regarding the probababilty of long term carcinogenicity and reproductive toxicity.

Approved by FDA in 1989

Indications:

CMV retinitis in immunocompromised patients

Dosage:

Do not administer by rapid or bolus IV injection. Toxicity may be increased as a result of excessive plasma levels. Recommended initial dose is 5mg/kg (given IV at aconstant rate over 1 hour) every 12 hours for 14 to 21 days.

Overdosage-

Symptoms Oral- no reports of overdosage with ganciclovir . Doses as high as 6000mg/day did not result in overt toxicity other than transcient neutropenia IV- overdose with IV ganciclovir has been reported in 17 patients (13 adults and 4 children < 2 years of age)

Treatment

1. Dialysis may be useful in reducing serum concentrations

2. Adequate hydrationshould be maintained

3. Consider theuse of hematopoietic growth factors.

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 (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.

1. Ganciclovir is not a treatment for CMV retinitis, and immunocompromised patients may continue to experience progression of retinitis during or following treatment

2. Advise patients to take oral ganciclovir with food to maximise bioavailability.

3.Advise patients that granciclovir may cause infertility. Advise women of child bearing potential that gancoclovir should not used during pregnancy.

4. Although there is no information, consider Ganciclovir as a potential carcinogen

5.Allergies- tell your doctor if you have ever had any unusual or allergic reaction to acyclovir or ganciclovir

6.Pregnancy - use to be avoided 6.Breast feeding-breast feedinf should be stopped during treatment.

7. Children -

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

8. 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 ganclovir by injection,

it is especially important that your doctor know that you are taking any of the following-

Amphotericin B by injection or Antineoplastics or Antithyroid agents or Azathioprine or Chloramphenicol or Colchicine or Cyclophosphamide or Flucytosine or Interferon or Mercaptopurine or Zidovudine -

Caution should be used if these medicines anfd angciclovir are used together Carmusatine, Cisplatin, combination of medicines containg acetaminophen and aspirin or other salicylates Cyclosporine or Deferoxamine or Gold salts or inflammation or pain medicines or Lithium or Penicillamine or Streptozocin or Tiopronin - use of these medicines may increase the chance of side effects affecting the kidneys Methotrexate or Plicamycin - these medicines may increase the chance of side efects afecting the blood and kidneys

9. Other medical problems -

Tell your doctor if you have any other medical problems especially - Kidney disease or Low platelet count or Low white blood cell counts - Ganciclovir may make these blood disesaes thsat you have worse.

10. Dose -

The dose of ganciclovir will be different for different patients. Follow your doctors order.

11. 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.

12. 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.

13. Outdated medicines -

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

14. Interaction with food -

Absorption is unaffected by food. May be taken with meals

Pharmacology:

Ganciclovir is a synthetic guanidine derivative against cytomegalovirus, is an acyclic analog that inhibits replication of virus herpes virus both in vivo and vitro . Sensitive human virus include CMV, herpes simplex-1 and -2, herpes virus type 6, varicela zoster and hepatitis B virus. Pharmacokinetics: The absolute bioavailability of oral gangciclovir under fasting conditions was ~ 5% and following food it was 6% to 9%. Following oral administration, of a single 1000mg dose, 86% of the administered dose was recovered in feces and 5% was recovered in the urine.

Oral ganciclovir to be taken with food to maximize bioavailability

Pregnancy:

Excercise caution.Use during pregnancy based on potential benefits

Lactation:

Instruct mothers to discontinue nursing if they are receiving ganciclovir. Children- Safety and efficacy have not been established. The use of gancoclovir in children warrants extreme caution regarding the probababilty of long term carcinogenicity and reproductive toxicity.