Interacting drugs- summary 

Didanosine+

+ Fluoroquinolnes
   Plasma conc of quinolone antibiotics decreased when
   administered with antacids containing aluminium or magnesium.
    Do not administer quinolone antibiotics within 2 hours of        
     taking didanosine tablets

 +Tetracyclines
     Do not simultaneously administer didanosine tablets or
     pediatric  powder for oral solution with tetracycline
            
                                                

Major toxicites are pancreatitis and peripheral neuropathy

Diarrhea 28% neuropathy all grades 20% chills/fever 12% rash/pruritus 9% abdominal pain 7% asthenia 7% headache 7% pain 7% nausea/vomiting 7% infection 6% pancreatitis 6% pneumonia 5% sarcoma 3% myopathy 3% anorexia 2% dry mouth 2% convulsion 2%

Hypersensitivity to the drug

Special precautions:

Periphreal neuropathy, Pancreatitis, Hepatic failure,renal function impairment

Opportunistic infections- patients receiving didanosine or any other antiretroviral therapy may continue to develop oppurtunistic infections and other complications of HIV infection and therefore, should remain under close clinical observation by physician experienced in treatment of patients with associated HIV diseases.

Progression of HIV infections- at present there are no results from controlled studies regarding the effect of didanosine therapy on the clinical progression of HIV infection, such as incidence of oppurtunistic infections and survival.

Phenylketonuria- didanosine tablets contain 22.5mg phenyalanine (33.7 mg in the 150mg tablet)

Sodium restriced diets- each buffered tablet contains 264.5 mg sodium. Each single dose packet of buffered powder for oral solution contains 1380 mg sodium.

Hyperuricemia- didanosine has been associated with asymptomatic hyperuricemia, consider suspendig treatment if clinical measures aimed at reducing uric acid levels fail.

Diarrhea- If diarrhea develops in a patient receiving buffered powder for oral solution, consider a trial of chewable/dispersable buffered tablets.

Warnings-

Peripheral neuropathy- occurs in patients with didanosine, the frequency appears to be dose-related. Monitor patients for the development of neuropathy that is characterized by distal numbness, tingling or pain in the feet or hands.

Pancreatitis- which has been fatal in some cases is the major clinical toxicity associated with didanosine therapy. Pancreatitis must be considered whenever a patient receiving didanosine develops abdominal pain, nausea, vomiting,or elevated biochemical markers.

Hepatic failure- fatal liver failure of unknown etiology occured during didanosine therapy in 1/170 patients in Phase I studies.

Retinal depigmentation- children receiving didanosine should undergo dilated retinal examination every 6 months of if a change in vision occurs.

Myopathy- human myyolpathy has been associated with administration of other nucleoside analogs. Retinal function impairment- patients with renal impairment (serum creatinine > 1.5mg/dl or creatinine clearance < 60ml/min ) may be at greater risk of toxicity from didanosine due to decreased drug clearance.

Hepatic function impairment- patients with hepatic impairment may be at greater risk for toxicity due to altered metabolism, a dose reduction may be necessary.

Pregnancy- Use during pregnancy only if claerly indicated.

Lactation- because of the potential for serious adverse reactions from didanosine in nursing infants instruct mothers to discontinue nursing when taking didanosine.

Children- can be administered under proper medical supervision.

Approved by FDA in October 1991

Indications:

HIV infections

Dosage:

Use a 12 hour dosing interval.

Take 2 tablets at each dose so that adequate buffering is provided to prevent gastric acid degradation of didanosine

Patients more than 60kg- 200mg bid, buffered powdr 250mg bid

Below 60kg- 125mg bid, 167mg bid buffered powder

Overdosage

There is no specific antidote. Experience with phase I clinical studies in which didanosine was initially administred at doses 10 times the currently recommended dose indicates that the complications of chronic overdose would include pancreatitis,peripheral neuropathy, diarrhea, hyperuricemia,or possibly hepatic dysfunction. It is not known whether didanosine is dialyzable by peritoneal or hemodialysis.

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.

DIDANOSINE-

1. Allergies- Tell your doctor if you have ever had any unusual or allergic reactions to didanozine or other related medicines. Also tell your doctor if youn are allergic to any other substances such as foods, preservatives or dyes.

2. Diet- Makesure that your doctor knows that you are on specialdiet, such as low sodium, diet. Didanosine chewable tabtets and oral solution packets containlarge amounts of sodium.

3. Pregnancy- didanosine crosses the placenta. However, didanosine has notbshown to cause birth defects or other problems in animal studies. Also it is not known whether didanosine reduces the chance that a baby born to an infected mother will also be infected

3. Breast feeding- talk to your doctor first if you are thinking of breast feeding your baby.

4. Children- didanosine can cause serious side effects in any patient. Your child must be carefully followed and frequently seen by your doctor while taking didanosine

5. Elderly- no specific information comparing use of diazoxide in the elderly in other age groups

6. Other medicines- tell your doctor if you are taking any other medicines -

Alcohol or Asparaginase or Azathioprine or Estrogens or Furosemide or Methyldopa or Pentamidine or Sulfonamides or Sulindac or Thiazide duretics or Valproic acid or use of these medicines with didanosine may increase the chance of pancreatitis

 7. Other medical problems- tell your doctor if you have any other medical problems- Alcoholism active or Heart disease or High blood pressure Kidney disease or Liver disease Toxemia during pregnancy - salt contained in the didanosine tabltes and the oral solution packets may make the conditions worse

 8. Missed dose- If you miss a dose of this medicine take it as soon as possible. However if it is almost time for your next dose go back to your regular dosing schedule. Do not double doses.

Pharmacology:

Didanosine is synthetic purine neucloside analog of deoxyadenosine, active against HIV virus. It inhibit in vitro replication of HIV.

Pharmacokinetics:

Didanosine is rapidly degraded at acidic pH. Therefore, all oral preparations contain buffering agents.

Ingestion of didanosine with food reduces the absorption of didanosine by as much as 50% Therefore administer on an empty stomach.

Pregnancy

Use during pregnancy only when required Lactation- Because of the potential for serious adverse reactions from didanosine in nursing infants , instruct mothers to discontinue nursing when taking didanosine.

Children

Can be administered under proper medical supervision.Pregnancy: