Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Kaletra

Kaletra 100 mg/25 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 77–78

HOS-109062 · Präparat HOS-093083

77  Venetoclax Increased plasma concentrations of venetoclax. Increased risk of tumor lysis syndrome at the dose initiation and during the ramp-up phase (see section 4.5). Anti-gout Colchicine Increased plasma concentrations of colchicine. Potential for serious and/or life-threatening reactions in patients with renal and/or hepatic impairment (see sections 4.4 and 4.5). Antihistamines Astemizole, terfenadine Increased plasma concentrations of astemizole and terfenadine. Thereby, increasing the risk of serious arrhythmias from these agents (see section 4.5). Antipsychotics/ Lurasidone Increased plasma concentrations of Neuroleptics lurasidone which may increase the potential for serious and/or life- threatening reactions (see section 4.5). Pimozide Increased plasma concentrations of pimozide. Thereby, increasing the risk of serious haematologic abnormalities, or other serious adverse effects from this agent (see section 4.5). Quetiapine Increased plasma concentrations of quetiapine which may lead to coma. The concomitant administration with quetiapine is contraindicated (see section 4.5). Ergot alkaloids Dihydroergotamine, ergonovine, Increased plasma concentrations of ergot ergotamine, methylergonovine derivatives leading to acute ergot toxicity, including vasospasm and ischaemia (see section 4.5). GI motility agent Cisapride Increased plasma concentrations of cisapride. Thereby, increasing the risk of serious arrhythmias from this agent (see section 4.5). Hepatitis C virus direct Elbasvir/grazoprevir Increased risk of alanine transaminase acting antivirals (ALT) elevations (see section 4.5). Lipid-modifying agents

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): quetiapine (HOS-086150) elbasvir (HOS-108814) methylergonovine (HOS-086155) cisapride (HOS-085610) hepatitis C virus (HOS-108813) ergot alkaloids (HOS-108807) venetoclax (HOS-086143) lead (HOS-085592) grazoprevir (HOS-108815) pimozide (HOS-085600) colchicine (HOS-086147) astemizole (HOS-085608) ergotamine (HOS-086154) terfenadine (HOS-085607) lurasidone (HOS-086148) ergonovine (HOS-086153) dihydroergotamine (HOS-086152) alanine (HOS-088949)

Gegenanzeigen · Kaletra

Kaletra 100 mg/25 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 78

HOS-109063 · Präparat HOS-093083

HMG Co-A Reductase Lovastatin, simvastatin Increased plasma concentrations of Inhibitors lovastatin and simvastatin; thereby, increasing the risk of myopathy including rhabdomyolysis (see section 4.5). Microsomal triglyceride Lomitapide Increased plasma concentrations of transfer protein (MTTP) lomitapide (see section 4.5). inhibitor

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): lovastatin (HOS-086157) lomitapide (HOS-086160) simvastatin (HOS-086158)

Gegenanzeigen · Kaletra

Kaletra 100 mg/25 mg film-coated tablets · Abschnitt 4.3 · PDF-Seite 78–79

HOS-109064 · Präparat HOS-093083

78  Phosphodiesterase Avanafil Increased plasma concentrations of (PDE5) inhibitors avanafil (see sections 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 sections 4.4 and 4.5) Sedatives/hypnotics Oral midazolam, triazolam Increased plasma concentrations of oral midazolam and triazolam. Thereby, increasing the risk of extreme sedation and respiratory depression from these agents. For caution on parenterally administered midazolam, see section 4.5. Lopinavir/ritonavir medicinal product level decreased Herbal products 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 lopinavir and ritonavir (see section 4.5).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): avanafil (HOS-086161) sildenafil (HOS-086162) triazolam (HOS-086168) midazolam (HOS-086167) vardenafil (HOS-086163)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 10

HOS-108830 · Präparat HOS-093083

Kaletra contains lopinavir and ritonavir, both of which are inhibitors of the P450 isoform CYP3A in vitro. Co-administration of Kaletra and medicinal products primarily metabolised by CYP3A may result in increased plasma concentrations of the other medicinal product, which could increase or prolong its therapeutic and adverse reactions. Kaletra does not inhibit CYP2D6, CYP2C9, CYP2C19, CYP2E1, CYP2B6 or CYP1A2 at clinically relevant concentrations (see section 4.3).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 10

HOS-108831 · Präparat HOS-093083

Kaletra has been shown in vivo to induce its own metabolism and to increase the biotransformation of some medicinal products metabolised by cytochrome P450 enzymes (including CYP2C9 and CYP2C19) and by glucuronidation. This may result in lowered plasma concentrations and potential decrease of efficacy of co-administered medicinal products.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 10

HOS-108832 · Präparat HOS-093083

Medicinal products that are contraindicated specifically due to the expected magnitude of interaction and potential for serious adverse events are listed in section 4.3.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 10

HOS-108833 · Präparat HOS-093083

Known and theoretical interactions with selected antiretrovirals and non-antiretroviral medicinal products are listed in the table below. This list is not intended to be inclusive or comprehensive. Individual SmPCs should be consulted.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 10–11

HOS-108834 · Präparat HOS-093083

10 Interaction table

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 11

HOS-108835 · Präparat HOS-093083

Interactions between Kaletra and co-administered medicinal products are listed in the table below (increase is indicated as “↑”, decrease as “↓”, no change as “↔”, once daily as “QD”, twice daily as “BID” and three times daily as "TID").

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 11

HOS-108836 · Präparat HOS-093083

Unless otherwise stated, studies detailed below have been performed with the recommended dosage of lopinavir/ritonavir (i.e. 400/100 mg twice daily).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 11

HOS-108837 · Präparat HOS-093083

Co-administered drug by Effects on drug levels Clinical recommendation therapeutic area concerning co-administration Geometric Mean Change (%) in with Kaletra AUC, Cmax, Cmin

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 11

HOS-108838 · Präparat HOS-093083

Mechanism of interaction Antiretroviral Agents Nucleoside/Nucleotide reverse transcriptase inhibitors (NRTIs) Lamivudine Lopinavir: ↔ No dose adjustment necessary.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): lamivudine (HOS-085829)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 11

HOS-108840 · Präparat HOS-093083

Abacavir, Zidovudine Abacavir, Zidovudine: The clinical significance of Concentrations may be reduced reduced abacavir and zidovudine due to increased glucuronidation concentrations is unknown. by lopinavir/ritonavir. Tenofovir disoproxil Tenofovir: No dose adjustment necessary. fumarate (DF), 300 mg QD AUC: ↑ 32% Higher tenofovir concentrations Cmax: ↔ could potentiate tenofovir (equivalent to 245 mg Cmin: ↑ 51% associated adverse events, tenofovir disoproxil) including renal disorders. Lopinavir: ↔ Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Efavirenz, 600 mg QD Lopinavir: See section 4.2 for Kaletra dosage AUC: ↓ 20% recommendation or consider Cmax: ↓ 13% alternative therapy. Cmin: ↓ 42% Nevirapine, 200 mg BID Lopinavir: See section 4.2 for Kaletra dosage AUC: ↓ 27% recommendation or consider Cmax: ↓ 19% alternative therapy. Cmin: ↓ 51% Etravirine Etravirine: No dose adjustment necessary AUC: ↓ 35% (Lopinavir/ritonavir tablet Cmin: ↓ 45% 400/100 mg BID) Cmax: ↓ 30%

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): tenofovir (HOS-088083) etravirine (HOS-088088) tenofovir disoproxil (HOS-108843) fumarate (HOS-108845) zidovudine (HOS-085837) efavirenz (HOS-087947) nevirapine (HOS-088064) abacavir (HOS-088077)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 11

HOS-108849 · Präparat HOS-093083

Lopinavir: AUC: ↔ Cmin: ↓ 20% Cmax: ↔ Rilpivirine Rilpivirine: Concomitant use of Kaletra with AUC: ↑ 52% rilpivirine causes an increase in the (Lopinavir/ritonavir Cmin: ↑ 74% plasma concentrations of capsule 400/100 mg BID) Cmax: ↑ 29% rilpivirine, but no dose adjustment is required. Lopinavir: AUC: ↔ Cmin: ↓ 11%

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): rilpivirine (HOS-088090)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 11–12

HOS-108851 · Präparat HOS-093083

11  Cmax: ↔

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 12

HOS-108852 · Präparat HOS-093083

(inhibition of CYP3A enzymes) HIV CCR5 – antagonist Maraviroc Maraviroc: The dose of maraviroc should be AUC: ↑ 295% decreased to 150 mg twice daily Cmax: ↑ 97% during co-administration with Due to CYP3A inhibition by Kaletra 400/100 mg twice daily. lopinavir/ritonavir. Integrase inhibitor Raltegravir Raltegravir: No dose adjustment necessary AUC: ↔ Cmax: ↔ C12: ↓ 30% Lopinavir: ↔ Co-administration with other HIV protease inhibitors (PIs) According to current treatment guidelines, dual therapy with protease inhibitors is generally not recommended. Fosamprenavir/ ritonavir Fosamprenavir: Co-administration of increased (700/100 mg BID) Amprenavir concentrations are doses of fosamprenavir (1400 mg significantly reduced. BID) with Kaletra oral solution (Lopinavir/ritonavir (533/133 mg BID) to protease 400/100 mg BID) inhibitor-experienced patients resulted in a higher incidence of or gastrointestinal adverse events and elevations in triglycerides with the Fosamprenavir (1400 mg combination regimen without BID) increases in virological efficacy, when compared with standard (Lopinavir/ritonavir doses of fosamprenavir/ritonavir. 533/133 mg BID) Concomitant administration of these medicinal products is not recommended. Tipranavir/ritonavir Lopinavir: Concomitant administration of (500/100 mg BID) AUC: ↓ 55% these medicinal products is not Cmin: ↓ 70% recommended. Cmax: ↓ 47% Acid reducing agents Omeprazole (40 mg QD) Omeprazole: ↔ No dose adjustment necessary

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): protease (HOS-085623) maraviroc (HOS-086186) amprenavir (HOS-086183) raltegravir (HOS-086187) fosamprenavir (HOS-086182) tipranavir (HOS-086184) omeprazole (HOS-085912)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 12

HOS-108860 · Präparat HOS-093083

Lopinavir: ↔ Ranitidine (150 mg single Ranitidine: ↔ No dose adjustment necessary dose) Alpha1 adrenoreceptor antagonist Alfuzosin Alfuzosin: Concomitant administration of Due to CYP3A inhibition by Kaletra and alfuzosin is contra- lopinavir/ritonavir, concentrations indicated (see section 4.3) as of alfuzosin are expected to alfuzosin-related toxicity, increase. including hypotension, may be increased. Analgesics Fentanyl Fentanyl: Careful monitoring of adverse Increased risk of side-effects effects (notably respiratory (respiratory depression, sedation) depression but also sedation) is due to higher plasma recommended when fentanyl is concentrations because of

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): alfuzosin (HOS-086139) ranitidine (HOS-085660) fentanyl (HOS-086196)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 12–13

HOS-108863 · Präparat HOS-093083

12  CYP3A4 inhibition by concomitantly administered with lopinavir/ritonavir. Kaletra. Antianginal Ranolazine Due to CYP3A inhibition by The concomitant administration of lopinavir/ritonavir, concentrations Kaletra and ranolazine is of ranolazine are expected to contraindicated (see section 4.3). increase. Antiarrhythmics Amiodarone, Dronedarone Amiodarone, Dronedarone: Concomitant administration of Concentrations may be increased Kaletra and amiodarone or due to CYP3A4 inhibition by dronedarone is contraindicated (see lopinavir/ritonavir. section 4.3) as the risk of arrhythmias or other serious adverse reactions may be increased. Digoxin Digoxin: Caution is warranted and Plasma concentrations may be therapeutic drug monitoring of increased due to P-glycoprotein digoxin concentrations, if inhibition by lopinavir/ritonavir. available, is recommended in case The increased digoxin level may of co-administration of Kaletra and lessen over time as P-gp digoxin. Particular caution should induction develops. be used when prescribing Kaletra in patients taking digoxin as the acute inhibitory effect of ritonavir on P-gp is expected to significantly increase digoxin levels. Initiation of digoxin in patients already taking Kaletra is likely to result in lower than expected increases of digoxin concentrations. Bepridil, Systemic Bepridil, Systemic Lidocaine, Caution is warranted and Lidocaine, and Quinidine Quinidine: therapeutic drug concentration Concentrations may be increased monitoring is recommended when when co-administered with available. lopinavir/ritonavir. Antibiotics Clarithromycin Clarithromycin: For patients with renal impairment Moderate increases in (CrCL < 30 ml/min) dose reduction clarithromycin AUC are expected of clarithromycin should be due to CYP3A inhibition by considered (see section 4.4). lopinavir/ritonavir. Caution should be exercised in administering clarithromycin with Kaletra to patients with impaired hepatic or renal function. Anticancer agents and kinase inhibitors Abemaciclib Serum concentrations may be Co-administration of abemaciclib increased due to CYP3A and Kaletra should be avoided. If inhibition by ritonavir. this co-administration is judged unavoidable, refer to the abemaciclib SmPC for dosage adjustment recommendations. Monitor for ADRs related to abemaciclib. Apalutamide Apalutamide is a moderate to Decreased exposure of Kaletra may strong CYP3A4 inducer and this result in potential loss of may lead to a decreased exposure virological response. of lopinavir/ritonavir.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): dronedarone (HOS-086144) abemaciclib (HOS-086209) lidocaine (HOS-108866) apalutamide (HOS-086212) bepridil (HOS-085612) quinidine (HOS-085593) digoxin (HOS-086172) lead (HOS-085592) clarithromycin (HOS-084517) amiodarone (HOS-085596) ranolazine (HOS-086141)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 13–14

HOS-108871 · Präparat HOS-093083

13  In addition, co-administration of Serum concentrations of apalutamide and Kaletra may lead apalutamide may be increased to serious adverse events including due to CYP3A inhibition by seizure due to higher apalutamide lopinavir/ritonavir. levels. Concomitant use of Kaletra with apalutamide is not recommended. Afatinib Afatinib: Caution should be exercised in AUC: ↑ administering afatinib with Kaletra. (Ritonavir 200 mg twice Cmax: ↑ Refer to the afatinib SmPC for daily) dosage adjustment The extent of increase depends on recommendations. Monitor for the timing of ritonavir ADRs related to afatinib. administration.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): apalutamide (HOS-086212) lead (HOS-085592) afatinib (HOS-086207)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 14

HOS-108873 · Präparat HOS-093083

Due to BCRP (breast cancer resistance protein/ABCG2) and acute P-gp inhibition by lopinavir/ritonavir. Ceritinib Serum concentrations may be Caution should be exercised in increased due to CYP3A and administering ceritinib with P-gp inhibition by Kaletra. Refer to the ceritinib lopinavir/ritonavir. SmPC for dosage adjustment recommendations. Monitor for ADRs related to ceritinib. Most tyrosine kinase Most tyrosine kinase inhibitors Careful monitoring of the tolerance inhibitors such as dasatinib such as dasatinib and nilotinib, of these anticancer agents. and nilotinib, vincristine, also vincristine and vinblastine: vinblastine Risk of increased adverse events due to higher serum concentrations because of CYP3A4 inhibition by lopinavir/ritonavir. Encorafenib Serum concentrations may be Co-administration of encorafenib increased due to CYP3A with Kaletra may increase inhibition by lopinavir/ritonavir. encorafenib exposure which may increase the risk of toxicity, including the risk of serious adverse events such as QT interval prolongation. Co-administration of encorafenib and Kaletra should be avoided. If the benefit is considered to outweigh the risk and Kaletra must be used, patients should be carefully monitored for safety. Fostamatinib Increase in fostamatinib Co-administration of fostamatinib metabolite R406 exposure. with Kaletra may increase fostamatinib metabolite R406 exposure resulting in dose-related adverse events such as hepatotoxicity, neutropenia, hypertension, or diarrhoea. Refer to the fostamatinib SmPC for dose reduction recommendations if such events occur.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): ceritinib (HOS-086215) dasatinib (HOS-086217) vinblastine (HOS-086220) vincristine (HOS-086219) encorafenib (HOS-086222) tyrosine (HOS-108875) nilotinib (HOS-086218) fostamatinib (HOS-086224)