Contraindications : התוויות נגד

4             CONTRAINDICATIONS

REYATAZ is contraindicated:

•   in patients with previously demonstrated clinically significant hypersensitivity (eg, Stevens- Johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of the components of REYATAZ capsules [see Warnings and Precautions (5.2)].
•   when coadministered with drugs that are highly dependent on CYP3A or UGT1A1 for clearance, and for which elevated plasma concentrations of the interacting drugs are associated with serious and/or life-threatening events (see Table 6).
•   when coadministered with drugs that strongly induce CYP3A and may lead to lower exposure and loss of efficacy of REYATAZ (see Table 6).

Table 6 displays drugs that are contraindicated with REYATAZ.
Table 6:              Drugs that are Contraindicated with REYATAZ (Information in the table applies to REYATAZ with or without ritonavir, unless otherwise indicated)
Drugs within class that are
Drug Class           contraindicated with REYATAZ                        Clinical Comment Alpha 1-             Alfuzosin                       Potential for increased alfuzosin concentrations, which can Adrenoreceptor                                       result in hypotension.
Antagonist
Antimycobacterials   Rifampin                        Rifampin substantially decreases plasma concentrations of atazanavir, which may result in loss of therapeutic effect and development of resistance.
Antineoplastics      Irinotecan                      Atazanavir inhibits UGT1A1 and may interfere with the metabolism of irinotecan, resulting in increased irinotecan toxicities.
Antipsychotics       Lurasidone                       Potential for serious and/or life-threatening reactions if REYATAZ is coadministered with ritonavir.
Table 6:                  Drugs that are Contraindicated with REYATAZ (Information in the table applies to REYATAZ with or without ritonavir, unless otherwise indicated)
Drugs within class that are
Drug Class               contraindicated with REYATAZ                               Clinical Comment Pimozide                               Potential for serious and/or life-threatening reactions such as cardiac arrhythmias.


Benzodiazepines          Triazolam, orally administered        Triazolam and orally administered midazolam are midazolama                            extensively metabolized by CYP3A4. Coadministration of triazolam or orally administered midazolam with
REYATAZ may cause large increases in the concentration of these benzodiazepines. Potential for serious and/or life- threatening events such as prolonged or increased sedation or respiratory depression.
Ergot Derivatives        Dihydroergotamine, ergotamine,        Potential for serious and/or life-threatening events such as ergonovine, methylergonovine          acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues.
GI Motility Agent        Cisapride                             Potential for serious and/or life-threatening reactions such as cardiac arrhythmias.
Hepatitis C Direct-      Elbasvir/grazoprevir                  May increase the risk of ALT elevations due to a Acting Antivirals                                              significant increase in grazoprevir plasma concentrations.
Glecaprevir/pibrentasvir              May increase the risk of ALT elevations due to an increase in glecaprevir and pibrentasvir concentrations.
Herbal Products          St. John’s wort (Hypericum            Coadministration of St. John’s wort and REYATAZ may perforatum)                           result in loss of therapeutic effect and development of resistance.
HMG-CoA Reductase        Lovastatin, simvastatin               Potential for serious reactions such as myopathy, including Inhibitors                                                     rhabdomyolysis.


PDE5 Inhibitor           Sildenafilb* when dosed for the       Potential for sildenafil-associated adverse events (which treatment of pulmonary arterial       include visual disturbances, hypotension, priapism, and hypertension                          syncope).
Protease Inhibitors      Indinavir                             Both REYATAZ and indinavir are associated with indirect (unconjugated) hyperbilirubinemia.
Non-nucleoside           Nevirapine                            Nevirapine substantially decreases atazanavir exposure Reverse Transcriptase                                          which may result in loss of therapeutic effect and Inhibitors                                                     development of resistance. Potential risk for nevirapine- associated adverse reactions due to increased nevirapine exposures.
a
See Drug Interactions, Table 16 (7) for parenterally administered midazolam.
b
See Drug Interactions, Table 16 (7) for sildenafil* when dosed for erectile dysfunction.