Contraindications : התוויות נגד

4.3   Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
When ritonavir is used as a pharmacokinetic enhancer of other PIs, consult the prescribing information of the co-administered protease inhibitor for contraindications.

Ritonavir should not be given as a pharmacokinetic enhancer or as an antiretroviral agent to patients with decompensated liver disease.

In vitro and in vivo studies have demonstrated that ritonavir is a potent inhibitor of CYP3A- and CYP2D6- mediated biotransformations. The following medicines are contraindicated when used with ritonavir and unless otherwise noted, the contraindication is based on the potential for ritonavir to inhibit metabolism of the co-administered medicinal product, resulting in increased exposure to the co-administered medicinal product and risk of clinically significant adverse effects.
The enzyme-modulating effect of ritonavir may be dose dependent. For some products, contraindications may be more relevant when ritonavir is used as an antiretroviral agent than when ritonavir is used as a pharmacokinetic enhancer (e.g. rifabutin and voriconazole):


Medicinal Product       Medicinal Products        Rationale
Class                   within Class
Concomitant medicinal product levels increased or decreased
α1-Adrenoreceptor      Alfuzosin               Increased plasma concentrations of alfuzosin which Antagonist                                     may lead to severe hypotension (see section 4.5).
Analgesics              Pethidine,                Increased plasma concentrations of norpethidine and propoxyphene              propoxyphene. Thereby, increasing the risk of serious respiratory depression or haematologic abnormalities,
or other serious adverse effects from these agents.
Antianginal             Ranolazine                Increased plasma concentrations of ranolazine which may increase the potential for serious and/or life- threatening reactions (see section 4.5).
Anticancer              Neratinib                 Increased plasma concentrations of neratinib which may increase the potential for serious and/or life- threatening reactions including hepatotoxicity (see section 4.5).
Venetoclax                Increased plasma concentrations of venetoclax.
Increased risk of tumor lysis syndrome at the dose initiation and during the dose-titration phase (see section 4.5).
Antiarrhythmics         Amiodarone, bepridil,     Increased plasma concentrations of amiodarone, dronedarone,              bepridil, dronedarone, encainide, flecainide, encainide, flecainide,    propafenone, quinidine. Thereby, increasing the risk of propafenone,              arrhythmias or other serious adverse effects from these quinidine                 agents.
Antibiotic              Fusidic Acid              Increased plasma concentrations of fusidic acid and ritonavir.
Antifungal              Voriconazole              Concomitant use of ritonavir (400 mg twice daily and more) and voriconazole is contraindicated due to a reduction in voriconazole plasma concentrations and possible loss of effect (see section 4.5).
Antihistamines          Astemizole,               Increased plasma concentrations of astemizole and terfenadine               terfenadine. Thereby, increasing the risk of serious arrhythmias from these agents.
Anti-gout               Colchicine                Potential for serious and/or life-threatening reactions in patients with renal and/or hepatic impairment (see sections 4.4 and 4.5).
Antimycobacterial       Rifabutin                 Concomitant use of ritonavir (500 mg twice daily) dosed as an antiretroviral agent and rifabutin due to an increase of rifabutin serum concentrations and risk of adverse reactions including uveitis (see section 4.4).
Recommendations regarding use of ritonavir dosed as a pharmacokinetic enhancer with rifabutin are noted in section 4.5.
Antipsychotics/         Lurasidone                Increased plasma concentrations of lurasidone which Neuroleptics                                      may increase the potential for serious and/or life- threatening reactions (see section 4.5).
Clozapine, pimozide       Increased plasma concentrations of clozapine and pimozide. Thereby, increasing the risk of serious
haematologic abnormalities, or other serious adverse effects from these agents.
Quetiapine                 Increased plasma concentrations of quetiapine which may lead to coma. The concomitant administration with quetiapine is contraindicated (see section 4.5).
Ergot Derivatives        Dihydroergotamine,         Increased plasma concentrations of ergot derivatives ergonovine,                leading to acute ergot toxicity, including vasospasm ergotamine,                and ischaemia.
methylergonovine
GI motility agent        Cisapride                  Increased plasma concentrations of cisapride. Thereby, increasing the risk of serious arrhythmias from this agent.
Lipid-modifying agents

HMG Co-A Reductase       Lovastatin,                Increased plasma concentrations of lovastatin and Inhibitors               simvastatin                simvastatin; thereby, increasing the risk of myopathy including rhabdomyolysis (see section 4.5).
Microsomal triglyceride transfer protein (MTTP)           Lomitapide                 Increased plasma concentrations of lomitapide (see inhibitor                                           section 4.5).
PDE5 inhibitors          Avanafil                   Increased plasma concentrations of avanafil (see section 4.4. and 4.5).
Sildenafil                 Contraindicated when used for the treatment of pulmonary arterial hypertension (PAH) only.
Increased plasma concentrations of sildenafil.
Thereby, increasing the potential for sildenafil- associated adverse events (which include hypotension and syncope). See section 4.4 and section 4.5 for co- administration of sildenafil in patients with erectile dysfunction.
Vardenafil                 Increased plasma concentrations of vardenafil (see section 4.4. and 4.5).
Sedatives/hypnotics      Clorazepate,               Increased plasma concentrations of clorazepate, diazepam, estazolam,       diazepam, estazolam, flurazepam, oral midazolam and flurazepam, oral           triazolam. Thereby, increasing the risk of extreme midazolam and              sedation and respiratory depression from these agents.
triazolam                  (For caution on parenterally administered midazolam, see section 4.5.).


Ritonavir medicinal product level decreased
Herbal Preparation      St. John's Wort             Herbal preparations containing St John's wort (Hypericum perforatum) due to the risk of decreased plasma concentrations and reduced clinical effects of ritonavir (see section 4.5).