Crixivan

CRIXIVAN should be administered by physicians who are experienced in the treatment of HIV infection. On the basis of current pharmacodynamic data, indinavir must be used in combination with other antiretroviral agents. 1). Posology The recommended dose of indinavir is 800 mg orally every 8 hours.

Data from published studies suggest that CRIXIVAN 400 mg in combination with ritonavir 100 mg, both administered orally twice daily, may be an alternative dosing regimen. 2). 5). Special populations Hepatic impairment In patients with mild–to–moderate hepatic impairment due to cirrhosis, the dose of indinavir should be reduced to 600 mg every 8 hours.

2). 4). 2). 2. Method of administration The hard capsules should be swallowed whole. Since CRIXIVAN must be taken at intervals of 8 hours, a schedule convenient for the patient should be developed. For optimal absorption, CRIXIVAN should be administered without food but with water 1 hour before or 2 hours after a meal.

Alternatively, CRIXIVAN may be administered with a low–fat, light meal. If co-administered with ritonavir, CRIXIVAN may be administered with or without food. 5 litres of liquids during the course of 24 hours.

4). Clinical adverse reactions reported by the investigators as possibly, probably, or definitely related to CRIXIVAN in  5 % of patients treated with CRIXIVAN monotherapy or in combination with NRTI(s) (n = 309) for 24 weeks are listed below.

Many of these adverse reactions were also identified as common pre–existing or frequently occurring medical conditions in this population. 7 %). With the exception of dry skin, rash, and taste perversion, the incidence of clinical adverse reactions was similar or higher among patients treated with antiretroviral nucleoside analogue controls than among patients treated with CRIXIVAN monotherapy or in combination with NRTI(s).

This overall safety profile remained similar for 107 patients treated with CRIXIVAN monotherapy or in combination with NRTI(s) for up to 48 weeks. Medicinal Product no longer authorised 18 In controlled clinical trials conducted world–wide, indinavir was administered alone or in combination with other antiretroviral agents (zidovudine, didanosine, stavudine, and/or lamivudine) to approximately 2,000 patients, the majority of whom were adult Caucasian males (15 % females).

Indinavir did not alter the type, frequency, or severity of known major adverse effects associated with the use of zidovudine, didanosine, or lamivudine. The following adverse reactions have been reported during clinical studies in adults and/or post- marketing use for CRIXIVAN monotherapy and/or CRIXIVAN with combination antiretroviral therapy (CART).

Very common (≥ 1/10); Common (≥ 1/100 to  1/10); Uncommon (≥ 1/1,000 to < 1/100); Rare (≥ 1/10,000 to  1/1,000); Very rare (< 1/10,000); not known (cannot be estimated from the available data). Adverse reactions have also been reported during post-marketing experience* as they are derived from spontaneous reports, incidences cannot be determined.

4 %). The cumulative frequency of nephrolithiasis events increases with increasing exposure to CRIXIVAN; however, the risk over time remains relatively constant. In some cases, nephrolithiasis has been associated with renal insufficiency or acute renal failure; in the majority of these cases renal insufficiency and acute renal failure were reversible.

g. for 1–3 days) during the acute episode of nephrolithiasis or discontinuation of therapy may be considered. Evaluation may consist of urinalysis, serum BUN and creatinine, and ultrasound of the bladder and kidneys. 8). , 1 to 3 days) during the acute episode of nephrolithiasis or discontinuation of therapy.

Cases of interstitial nephritis with medullary calcification and cortical atrophy have been observed in patients with asymptomatic severe leucocyturia (> 100 cells/high power field). In patients at increased risk, urinary screening should be considered.

If persistent severe leucocyturia is found, further investigation might be warranted. Medicinal products interactions Indinavir should be used cautiously with other medicinal products that are potent inducers of CYP3A4. 5). If indinavir is given with ritonavir, the potential interaction may be increased.

The Interactions section of the SPC for ritonavir should also be consulted for information about potential interactions. Atazanavir as well as indinavir are associated with indirect (unconjugated) hyperbilirubinemia due to inhibition of UDP-glucuronosyltransferase (UGT).

Combinations of atazanavir with or without ritonavir and Crixivan have not been studied and co-administration of these medicinal products is not recommended due to risk of worsening of these adverse reactions. Concomitant use of indinavir with lovastatin or simvastatin is not recommended due to an increased risk of myopathy including rhabdomyolysis.

Based on an interaction study with lopinavir/ritonavir, combination of rosuvastatin and protease inhibitors is not recommended. Caution must also be exercised if indinavir is used concurrently with atorvastatin. 5). 5). HIV Transmission While effective viral suppression with antiretroviral therapy has been proven to substantially reduce the risk of sexual transmission, a residual risk cannot be excluded.

1. Indinavir with or without ritonavir should not be administered concurrently with medicinal products with narrow therapeutic windows and which are substrates of CYP3A4. 5). 4). 5). 5). In addition, indinavir with ritonavir must not be administered with alfuzosin, meperidine, piroxicam, propoxyphene, bepridil, encainide, flecanide, propafenone, quinidine, fusidic acid, clozapine, clorazepate, diazepam, estazolam and flurazepam.

4). When CRIXIVAN is used with ritonavir, consult the Summary of Product Characteristics of ritonavir for additional contraindications.