Indinavir
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Indinavir |
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The information represented on this drug does not necessarily correspond
with the information that can be found in the Belgian scientific
leaflet.
Indinavir was approved by the FDA in March of 1996 for the treatment
of HIV infection when therapy is warranted. (106)
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USA (FDA)
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| Pharmaceutical co.: Merck & Co., Inc. | Belgium:
Reimbursable since April 1997 |
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| Active
Ingredient |
Dosage form;
Route |
Strength | ||||||
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Indinavir Sulfate | Capsule; Oral | 200MG | |||||
| Indinavir Sulfate | Capsule; Oral | 400MG | ||||||
Administering indinavir with meals containing high levels of fat and/or protein results in a significant decrease in the drug's oral bioavailability, but to increase compliance, indinavir may be given with small, low-protein, low-fat meals.(110) Indinavir is metabolized in the liver, primarily by the cytochrome P450 system. In patients with hepatic insufficiency due to cirrhosis, the indinavir dose should be reduced. (106)
The starting dosage of indinavir is 800 mg every 8 hours, 1 hour before or 2 hours after meals, or with a light snack (low fat, low protein). (100,106) Instruct the patient to consume 1,5 liters of extra fluids each day. (111)
Indinavir is relatively safe and well tolerated. Nephrolithiasis is
the most significant adverse effect. Approximately 5% of patients will
develop kidney stones during the first year of treatment. The stones are
composed of indinavir crystals that form in the collecting system. If symptoms
of kidney stones develop, temporary interruption of therapy (1 to 3 days)
may be considered during the acute episode, as suggested in the package
insert. Indinavir-associated nephrolithiasis is typically treated with
hydration and pain relief. To help prevent stone formation, patients should
drink at least 48 ounces of fluid (preferably water) throughout the day.
(100,106)
Asymptomatic hyperbilirubinemia has occured in aproximately 10% of
the patients treated with indinavir. In less than 1% of patients, this
finding was associated with elevations in transaminases. Hyperbilirubinemia
and nephrolithiasis occured more frequently at doses exceeding 2,4 g/day
compared to doses < 2,4 g/day. (114)
Hyperglycemia and new-onset diabetes mellitus has been reported with
ritonavir. (115)
Indinavir has also been associated with mild gastrointestinal symptoms,
including abdominal pain, nausea, vomiting, and gastroesophageal reflux.
Fatigue, flank pain, malaise, anorexia, dry mouth, back pain, headache,
insomnia, dizziness, somnolence and taste perversion. (114)
Mild to moderate elevation of indirect bilirubin is common, but it is not
associated with hepatitis or hepatic damage.(100,106,116)
Indinavir is metabolized by the cytochrome P450 3A4 enzyme system. Drugs
that induce the activity of this system (such as rifampin) may lead to
reduced plasma concentrations of indinavir, and possibly the rapid development
of drug resistance. Because ketoconazole inhibits the CYP3A4 pathway, it
may increase the plasma concentrations of indinavir. The coadministration
of ketoconazole and indinavir requires a reduction in the dose of indinavir.
Because of the potential interactions between indinavir and terfenadine,
cisapride, astemizole, triazolam, midazolam and rifampin, the manufacturer
recommends that these drugs wil not be administered concurrently with indinavir.
Indinavir appears to inhibit the P450 CYP3A4 system, thereby leading
to increased plasma levels of several coadministered drugs, including terfenadine,
astemizole, cisapride, triazolam, and midazolam. Coadministration of these
agents with indinavir is contraindicated. Due to its inhibitory effect
on CYP3A, indinavir increases the area under the curve of rifabutin 200%;
therefore, coadministration of these drugs requires decreasing the dose
of rifabutin by 50%.(106,114,116)
| Interactions with other antiretroviral agents | |
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