Interacting drugs- summary

Indinavir +

Astemizole / Cisapride/ Midazolam / Terfenadine/ Trizolam
Indinavir could result in inhibition of the metabolism of these drugs
and create the potential for serious life-threatening events.
 Indinavir should not be administered concurrently with these agents
    
Clarithomycin+  Indinavir
Coadmin resulted in an increase in indinavir AUC
 
Indinavir  +  Clarithromycin
 53% increase in clarithromycin AUC

Didanosine  +
If indinavir and didanosine are to be administered concomittantly
administer at least 1 hour apart on an empty  stomach, a normal
 (acidic) pH may be necessary for optimum absorption of indinavir,                                                                                         

Fluconazole +                                                                                                                  Concurrent use resulted in 19% decrease in indinavir AUC

Ketoconazole +                                                                                                             Cadmin resulted in a 68%+/-48% increase in indinavir AUC

Quinidine +                                                                                                                     Concurrent use resulted in a 10% increase in indinavir AUC

Rifampin +                                                                                                                   Rifampin is a potent inducer of P450 which could markedly                                          diminish plasma conc of indinavir, coadmin not recommended

Body as a whole-

Abdominal pain 9% asthenia/fatigue 4% flank pain 3%

GI -

Nausea 12% diarrhea 5% vomiting 4% acid regurgitation 2% anorexia 0.5% dry mouth 0.5%

CNS-

Headache 6% insomnia 3% dizziness 1% somnolence 1%

Miscellaneous-

Taste pervertion 3% back pain 2%

Rash, food allergy, hyperbilirubinemia and nephrolithiasis occured more frequently at doses > 2.4 g/day

Hypersensitivity to the drug

Special precautions:

Hyperbilirubinemia.- asaymptomatic hyperbilirubinemia (total bilirubin 2.5 mg/dl) reported predominantly as elevated indirect bilirubin has occured in 10% of patients,associated with elevations in ALT or AST.

Warnings

Concomittant agents- do not administer indinavir concurrently with terfenadine, astemizole, ciaspride, triazolam and midazolam because competition for CYP344 by indinavir could result in inhibition of the metabolism of these drugs and create the potential for serious or life-threatening events (eg. cardiac arrhythmias, prolonged sedation)

Renal function impairment- nephrolithiasis, including flank pain with or without hematuria (including microscopic hematuria ) has been reported in 4% of patients. In general these events are associated with renal dysfunction and resolved with hydration and temporary interrruption of therapy (eg. 1 to 3 days ).

To ensure adequate hydration, it is recommended that the patient drink at least 1.5 litres (48 ounces ) of liquids during the course of 24 hours.

Pregnancy- Use during pregnancy only if the potential benefit justifies risk to the fetus.

Lactation- Instruct mothers to discontinue nursing if they are receiving indinavir +

Children- Safety and efficacy have not been established

Approved by FDA on March 13,1996

HIV infections

Dosage:

Recommended dosage is 800mg (two 400mg capsules) orally every 8 hours.

Administer 1 hour before or 2 hours after a meal

Overdosage-

It is not known whether indanavir is dialyzable by peritoneal 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.

1. Indinavir is not cure for HIV and patients may continue to develop opportunistic infections and other complications

2.Advise patients to remain in care of a physician when using indinavir and not to modify or discontinue without consulting the physician

3. Indinavir capsule are sensitive to moisture. Instruct patients to store indinavir in the original container and keep a desiccant in the bottle.

4. To ensure adequate hydration, it is recommended that the patient drink at least 1.5 litres (48 ounces ) of liquids during the course of 24 hours.

Pharmacolgy:

Indinavir is an inhibitor of the human immunodeficiency virus (HIV) protease. HIV protease is an enzyme required for the proteolytic clevage of the viral polyprotein precursors into the individual functional proteins in infectious HIV.

Pharmacokinetics:

Indinavir is rapidly absorbed in the fasteds state with a time to peak plasma concentrations. Indinavir was bound to human plasma proteins over a concentration range of 81 to 16300nM

Advised to take without food but with water.

Pregnancy:

Use during pregnancy only when needed

Lactation:

Instruct mothers to discontinue the drug while nursing infants

Children-

Safety and efficacy have not been established