Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 14–15

HOS-108882 · Präparat HOS-093083

14 Ibrutinib Serum concentrations may be Co-administration of ibrutinib and increased due to CYP3A Kaletra may increase ibrutinib inhibition by lopinavir/ritonavir. exposure which may increase the risk of toxicity including risk of tumor lysis syndrome. Co-administration of ibrutinib and Kaletra should be avoided. If the benefit is considered to outweigh the risk and Kaletra must be used, reduce the ibrutinib dose to 140 mg and monitor patient closely for toxicity. Neratinib Serum concentrations may be Concomitant use of neratinib with increased due to CYP3A Kaletra is contraindicated due to inhibition by ritonavir. serious and/or life-threatening potential reactions including hepatotoxicity (see section 4.3). Venetoclax Due to CYP3A inhibition by Serum concentrations may be lopinavir/ritonavir. increased due to CYP3A inhibition by lopinavir/ritonavir, resulting in increased risk of tumor lysis syndrome at the dose initiation and during the ramp-up phase (see section 4.3 and refer to the venetoclax SmPC).

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): neratinib (HOS-086142) venetoclax (HOS-086143) ibrutinib (HOS-086226)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 15

HOS-108884 · Präparat HOS-093083

For patients who have completed the ramp-up phase and are on a steady daily dose of venetoclax, reduce the venetoclax dose by at least 75% when used with strong CYP3A inhibitors (refer to the venetoclax SmPC for dosing instructions). Patients should be closely monitored for signs related to venetoclax toxicities. Anticoagulants Warfarin Warfarin: It is recommended that INR Concentrations may be affected (international normalised ratio) be when co-administered with monitored. lopinavir/ritonavir due to CYP2C9 induction. Rivaroxaban Rivaroxaban: Co-administration of rivaroxaban AUC: ↑ 153% and Kaletra may increase (Ritonavir 600 mg twice Cmax: ↑ 55% rivaroxaban exposure which may daily) Due to CYP3A and P-gp increase the risk of bleeding. inhibition by lopinavir/ritonavir. The use of rivaroxaban is not recommended in patients receiving concomitant treatment with Kaletra (see section 4.4).

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): venetoclax (HOS-086143) rivaroxaban (HOS-086236) warfarin (HOS-085950)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 15–16

HOS-108886 · Präparat HOS-093083

15 Dabigatran etexilate, Dabigatran etexilate, Clinical monitoring and/or dose Edoxaban Edoxaban: reduction of the direct oral Serum concentrations may be anticoagulants (DOAC) should be increased due to P-gp inhibition considered when a DOAC by lopinavir/ritonavir. transported by P-gp but not metabolised by CYP3A4, including dabigatran etexilate and edoxaban, is co-administered with Kaletra. Anticonvulsants Phenytoin Phenytoin: Caution should be exercised in Steady-state concentrations was administering phenytoin with moderately decreased due to Kaletra. CYP2C9 and CYP2C19 induction by lopinavir/ritonavir. Phenytoin levels should be monitored when co-administering Lopinavir: with Kaletra. Concentrations are decreased due to CYP3A induction by When co-administered with phenytoin. phenytoin, an increase of Kaletra dosage may be envisaged. Dose adjustment has not been evaluated in clinical practice. Carbamazepine and Carbamazepine: Caution should be exercised in Phenobarbital Serum concentrations may be administering carbamazepine or increased due to CYP3A phenobarbital with Kaletra. inhibition by lopinavir/ritonavir. Carbamazepine and phenobarbital Lopinavir: levels should be monitored when Concentrations may be decreased co-administering with Kaletra. due to CYP3A induction by carbamazepine and phenobarbital. When co-administered with carbamazepine or phenobarbital, an increase of Kaletra dosage may be envisaged. Dose adjustment has not been evaluated in clinical practice

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): phenobarbital (HOS-085617) carbamazepine (HOS-085618) edoxaban (HOS-086234) dabigatran etexilate (HOS-086233) phenytoin (HOS-084531)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 16–17

HOS-108891 · Präparat HOS-093083

16 Lamotrigine and Valproate Lamotrigine: Patients should be monitored AUC: ↓ 50% closely for a decreased VPA effect Cmax: ↓ 46% when Kaletra and valproic acid or Cmin: ↓ 56% valproate are given concomitantly.

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): lamotrigine (HOS-086242) valproate (HOS-085955) valproic acid (HOS-088515)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 17

HOS-108895 · Präparat HOS-093083

Due to induction of lamotrigine In patients starting or stopping glucuronidation Kaletra while currently taking maintenance dose of lamotrigine: Valproate: ↓ lamotrigine dose may need to be increased if Kaletra is added, or decreased if Kaletra is discontinued; therefore plasma lamotrigine monitoring should be conducted, particularly before and during 2 weeks after starting or stopping Kaletra, in order to see if lamotrigine dose adjustment is needed. In patients currently taking Kaletra and starting lamotrigine: no dose adjustments to the recommended dose escalation of lamotrigine should be necessary. Antidepressants and Anxiolytics Trazodone single dose Trazodone: It is unknown whether the AUC: ↑ 2.4-fold combination of Kaletra causes a (Ritonavir, 200 mg BID) similar increase in trazodone Adverse events of nausea, exposure. The combination should dizziness, hypotension and be used with caution and a lower syncope were observed following dose of trazodone should be co-administration of trazodone considered. and ritonavir. Antifungals Ketoconazole and Ketoconazole, Itraconazole: High doses of ketoconazole and Itraconazole Serum concentrations may be itraconazole (> 200 mg/day) are increased due to CYP3A not recommended. inhibition by lopinavir/ritonavir. Voriconazole Voriconazole: Co-administration of voriconazole Concentrations may be decreased. and low dose ritonavir (100 mg BID) as contained in Kaletra should be avoided unless an assessment of the benefit/risk to patient justifies the use of voriconazole.

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): lamotrigine (HOS-086242) valproate (HOS-085955) ketoconazole (HOS-084513) voriconazole (HOS-084524) itraconazole (HOS-084516) trazodone (HOS-086251)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 17–18

HOS-108900 · Präparat HOS-093083

17 Anti-gout agents Colchicine single dose Colchicine: Concomitant administration of AUC: ↑ 3-fold Kaletra with colchicine in patients (Ritonavir 200 mg twice Cmax: ↑ 1.8-fold with renal and/or hepatic daily) Due to P-gp and/or CYP3A4 impairment is contraindicated due inhibition by ritonavir. to a potential increase of colchicine-related serious and/or life-threatening reactions such as neuromuscular toxicity (including rhabdomyolysis) (see sections 4.3 and 4.4). A reduction in colchicine dosage or an interruption of colchicine treatment is recommended in patients with normal renal or hepatic function if treatment with Kaletra is required. Refer to colchicine prescribing information. Antihistamines Astemizole Serum concentrations may be Concomitant administration of Terfenadine increased due to CYP3A Kaletra and astemizole and inhibition by lopinavir/ritonavir. terfenadine is contraindicated as it may increase the risk of serious arrhythmias from these agents (see section 4.3). Anti-infectives Fusidic acid Fusidic acid: Concomitant administration of Concentrations may be increased Kaletra with fusidic acid is contra- due to CYP3A inhibition by indicated in dermatological lopinavir/ritonavir. indications due to the increased risk of adverse events related to fusidic acid, notably rhabdomyolysis (see section 4.3). When used for osteo-articular infections, where the co- administration is unavoidable, close clinical monitoring for muscular adverse events is strongly recommended (see section 4.4). Antimycobacterials Bedaquiline Bedaquiline: Due to the risk of bedaquiline (single dose) AUC: ↑ 22% related adverse events, the Cmax: ↔ combination of bedaquiline and (Lopinavir/ritonavir Kaletra should be avoided. If the 400/100 mg BID, multiple A more pronounced effect on benefit outweighs the risk, dose) bedaquiline plasma exposures co-administration of bedaquiline may be observed during with Kaletra must be done with prolonged co-administration with caution. More frequent lopinavir/ritonavir. electrocardiogram monitoring and monitoring of transaminases is CYP3A4 inhibition likely due to recommended (see section 4.4 and lopinavir/ritonavir. refer to the bedaquiline SmPC).

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): fusidic acid (HOS-086146) bedaquiline (HOS-086268) colchicine (HOS-086147) astemizole (HOS-085608) terfenadine (HOS-085607)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 18–19

HOS-108902 · Präparat HOS-093083

18 Delamanid (100 mg BID) Delamanid: Due to the risk of QTc prolongation AUC: ↑ 22% associated with DM-6705, if (Lopinavir/ritonavir co-administration of delamanid 400/100 mg BID) DM-6705 (delamanid active with Kaletra is considered metabolite): necessary, very frequent ECG AUC: ↑ 30% monitoring throughout the full delamanid treatment period is A more pronounced effect on recommended (see section 4.4 and DM-6705 exposure may be refer to the delamanid SmPC). observed during prolonged co- administration with lopinavir/ritonavir. Rifabutin, 150 mg QD Rifabutin (parent drug and active When given with Kaletra the 25-O-desacetyl metabolite): recommended dose of rifabutin is AUC: ↑ 5.7-fold 150 mg 3 times per week on set Cmax: ↑ 3.5-fold days (for example Monday- Wednesday-Friday). Increased monitoring for rifabutin-associated adverse reactions including neutropenia and uveitis is warranted due to an expected increase in exposure to rifabutin. Further dosage reduction of rifabutin to 150 mg twice weekly on set days is recommended for patients in whom the 150 mg dose 3 times per week is not tolerated. It should be kept in mind that the twice weekly dosage of 150 mg may not provide an optimal exposure to rifabutin thus leading to a risk of rifamycin resistance and a treatment failure. No dose adjustment is needed for Kaletra.

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): rifabutin (HOS-086262)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 19–20

HOS-108904 · Präparat HOS-093083

19 Rifampicin Lopinavir: Co-administration of Kaletra with Large decreases in lopinavir rifampicin is not recommended as concentrations may be observed the decrease in lopinavir due to CYP3A induction by concentrations may in turn rifampicin. significantly decrease the lopinavir therapeutic effect. A dose adjustment of Kaletra 400 mg/400 mg (i.e. Kaletra 400/100 mg + ritonavir 300 mg) twice daily has allowed compensating for the CYP 3A4 inducer effect of rifampicin. However, such a dose adjustment might be associated with ALT/AST elevations and with increase in gastrointestinal disorders. Therefore, this co-administration should be avoided unless judged strictly necessary. If this co-administration is judged unavoidable, increased dose of Kaletra at 400 mg/400 mg twice daily may be administered with rifampicin under close safety and therapeutic drug monitoring. The Kaletra dose should be titrated upward only after rifampicin has been initiated (see section 4.4). Antipsychotics Lurasidone Due to CYP3A inhibition by The concomitant administration lopinavir/ritonavir, with lurasidone is contraindicated concentrations of lurasidone are (see section 4.3). expected to increase. Pimozide Due to CYP3A inhibition by Concomitant administration of lopinavir/ritonavir, Kaletra and pimozide is concentrations of pimozide are contraindicated as it may increase expected to increase. the risk of serious haematologic abnormalities or other serious adverse effects from this agent (see section 4.3) Quetiapine Due to CYP3A inhibition by Concomitant administration of lopinavir/ritonavir, Kaletra and quetiapine is concentrations of quetiapine are contraindicated as it may increase expected to increase. quetiapine-related toxicity.

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) pimozide (HOS-085600) lurasidone (HOS-086148)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 20–21

HOS-108905 · Präparat HOS-093083

20 Benzodiazepines Midazolam Oral Midazolam: Kaletra must not be co-administered AUC: ↑ 13-fold with oral midazolam (see section Parenteral Midazolam: 4.3), whereas caution should be AUC: ↑ 4-fold used with co-administration of Due to CYP3A inhibition by Kaletra and parenteral midazolam. lopinavir/ritonavir If Kaletra is co-administered with parenteral midazolam, it should be done in an intensive care unit (ICU) or similar setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Dosage adjustment for midazolam should be considered especially if more than a single dose of midazolam is administered. Beta2-adrenoceptor agonist (long acting) Salmeterol Salmeterol: The combination may result in Concentrations are expected to increased risk of cardiovascular increase due to CYP3A inhibition adverse events associated with by lopinavir/ritonavir. salmeterol, including QT prolongation, palpitations and sinus tachycardia. Therefore, concomitant administration of Kaletra with salmeterol is not recommended (see section 4.4). Calcium channel blockers Felodipine, Nifedipine, and Felodipine, Nifedipine, Clinical monitoring of therapeutic Nicardipine Nicardipine: and adverse effects is Concentrations may be increased recommended when these due to CYP3A inhibition by medicines are concomitantly lopinavir/ritonavir. administered with Kaletra. Corticosteroids Dexamethasone Lopinavir: Clinical monitoring of antiviral Concentrations may be decreased efficacy is recommended when due to CYP3A induction by these medicines are concomitantly dexamethasone. administered with Kaletra.

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): nifedipine (HOS-086289) nicardipine (HOS-090619) felodipine (HOS-108908) calcium (HOS-085615) salmeterol (HOS-086285) dexamethasone (HOS-084535) midazolam (HOS-086167)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 21–22

HOS-108912 · Präparat HOS-093083

21 Inhaled, injectable or Fluticasone propionate, 50 g Greater effects may be expected intranasal fluticasone intranasal 4 times daily: when fluticasone propionate is propionate, budesonide, Plasma concentrations ↑ inhaled. Systemic corticosteroid triamcinolone Cortisol levels ↓ 86% effects including Cushing's syndrome and adrenal suppression have been reported in patients receiving ritonavir and inhaled or intranasally administered fluticasone propionate; this could also occur with other corticosteroids metabolised via the P450 3A pathway e.g. budesonide and triamcinolone. Consequently, concomitant administration of Kaletra and these glucocorticoids is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects (see section 4.4). A dose reduction of the glucocorticoid should be considered with close monitoring of local and systemic effects or a switch to a glucocorticoid, which is not a substrate for CYP3A4 (e.g. beclomethasone). Moreover, in case of withdrawal of glucocorticoids progressive dose reduction may have to be performed over a longer period. Phosphodiesterase(PDE5) inhibitors Avanafil Avanafil: The use of avanafil with Kaletra is (ritonavir 600 mg BID) AUC: ↑ 13-fold contraindicated (see section 4.3). Due to CYP3A inhibition by 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): triamcinolone (HOS-086333) fluticasone (HOS-108914) fluticasone propionate (HOS-086331) avanafil (HOS-086161) budesonide (HOS-086332) propionate (HOS-108915) beclomethasone (HOS-086334)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 22–23

HOS-108919 · Präparat HOS-093083

22 Tadalafil Tadalafil: For the treatment of pulmonary AUC: ↑ 2-fold arterial hypertension: Due to CYP3A4 inhibition by Co-administration of Kaletra with lopinavir/ritonavir. sildenafil is contraindicated (see section 4.3). Co-administration of Sildenafil Sildenafil: Kaletra with tadalafil is not AUC: ↑ 11-fold recommended. Due to CYP3A inhibition by lopinavir/ritonavir. For erectile dysfunction: Particular caution must be used when prescribing sildenafil or tadalafil in patients receiving Kaletra with increased monitoring for adverse events including hypotension, syncope, visual changes and prolonged erection (see section 4.4). When co-administered with Kaletra, sildenafil doses must not exceed 25 mg in 48 hours and tadalafil doses must not exceed 10 mg every 72 hours

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): tadalafil (HOS-086316) sildenafil (HOS-086162)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 23

HOS-108921 · Präparat HOS-093083

Vardenafil Vardenafil: The use of vardenafil with Kaletra AUC: ↑ 49-fold is contraindicated (see section 4.3). Due to CYP3A inhibition by lopinavir/ritonavir. Ergot alkaloids Dihydroergotamine, Serum concentrations may be Concomitant administration of ergonovine, ergotamine, increased due to CYP3A Kaletra and ergot alkaloids are methylergonovine inhibition by lopinavir/ritonavir. contraindicated as it may lead to acute ergot toxicity, including vasospasm and ischaemia (see section 4.3). GI motility agent Cisapride Serum concentrations may be Concomitant administration of increased due to CYP3A Kaletra and cisapride is inhibition by lopinavir/ritonavir. contraindicated as it may increase the risk of serious arrhythmias from this agent (see section 4.3). HCV direct acting antivirals Elbasvir/grazoprevir Elbasvir: Concomitant administration of (50/200 mg QD) AUC: ↑ 2.71-fold elbasvir/grazoprevir with Kaletra Cmax: ↑ 1.87-fold is contraindicated (see section C24: ↑ 3.58-fold 4.3).

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): elbasvir (HOS-108814) methylergonovine (HOS-086155) cisapride (HOS-085610) ergot alkaloids (HOS-108807) lead (HOS-085592) grazoprevir (HOS-108815) ergotamine (HOS-086154) ergonovine (HOS-086153) dihydroergotamine (HOS-086152) vardenafil (HOS-086163)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 23

HOS-108922 · Präparat HOS-093083

Grazoprevir: AUC: ↑ 11.86-fold Cmax: ↑ 6.31-fold C24: ↑ 20.70-fold

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): grazoprevir (HOS-108815)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 23

HOS-108923 · Präparat HOS-093083

(combinations of mechanisms including CYP3A inhibition)

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 23

HOS-108924 · Präparat HOS-093083

Lopinavir: ↔

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 23–24

HOS-108925 · Präparat HOS-093083

23 Glecaprevir/pibrentasvir Serum concentrations may be Concomitant administration of increased due to P-glycoprotein, glecaprevir/pibrentasvir and BCRP and OATP1B inhibition by Kaletra is not recommended due lopinavir/ritonavir. to an increased risk of ALT elevations associated with increased glecaprevir exposure. Sofosbuvir/velpatasvir/ Serum concentrations of It is not recommended to voxilaprevir sofosbuvir, velpatasvir and coadminister Kaletra and voxilaprevir may be increased due sofosbuvir/velpatasvir/ to P-glycoprotein, BCRP and voxilaprevir. OATP1B1/3 inhibition by lopinavir/ritonavir. However, only the increase in voxilaprevir exposure is considered clinically relevant. HCV protease inhibitors Simeprevir 200 mg daily Simeprevir: It is not recommended to (ritonavir 100 mg BID) AUC: ↑ 7.2-fold co-administer Kaletra and Cmax: ↑ 4.7-fold simeprevir. Cmin: ↑ 14.4-fold Herbal products St John’s wort (Hypericum Lopinavir: Herbal preparations containing St perforatum) Concentrations may be reduced John’s wort must not be combined due to induction of CYP3A by the with lopinavir and ritonavir. If a herbal preparation St John’s wort. patient is already taking St John’s wort, stop St John’s wort and if possible check viral levels. Lopinavir and ritonavir levels may increase on stopping St John’s wort. The dose of Kaletra may need adjusting. The inducing effect may persist for at least 2 weeks after cessation of treatment with St John’s wort (see section 4.3). Therefore, Kaletra can be started safely 2 weeks after cessation of St John's wort. Immunosuppressants Cyclosporin, Sirolimus Cyclosporin, Sirolimus More frequent therapeutic (rapamycin), and (rapamycin), Tacrolimus: concentration monitoring is Tacrolimus Concentrations may be increased recommended until plasma levels due to CYP3A inhibition by of these products have been lopinavir/ritonavir. stabilised. Lipid lowering agents Lovastatin and Simvastatin Lovastatin, Simvastatin: Since increased concentrations of Markedly increased plasma HMG-CoA reductase inhibitors concentrations due to CYP3A may cause myopathy, including inhibition by lopinavir/ritonavir. rhabdomyolysis, the combination of these agents with Kaletra is contraindicated (see section 4.3). Lipid-modifying agents Lomitapide CYP3A4 inhibitors increase the Concomitant use of Kaletra with exposure of lomitapide, with lomitapide is contraindicated (see strong inhibitors increasing prescribing information for exposure approximately 27-fold. lomitapide) (see section 4.3). Due to CYP3A inhibition by lopinavir/ritonavir, concentrations

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): sofosbuvir (HOS-108928) protease (HOS-085623) lovastatin (HOS-086157) pibrentasvir (HOS-086298) lomitapide (HOS-086160) simvastatin (HOS-086158) glecaprevir (HOS-086297) voxilaprevir (HOS-108930) tacrolimus (HOS-085202) velpatasvir (HOS-108929) simeprevir (HOS-086302) sirolimus (HOS-085172)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 24–25

HOS-108934 · Präparat HOS-093083

24  of lomitapide are expected to increase. Atorvastatin Atorvastatin: The combination of Kaletra with AUC: ↑ 5.9-fold atorvastatin is not recommended. Cmax: ↑ 4.7-fold If the use of atorvastatin is Due to CYP3A inhibition by considered strictly necessary, the lopinavir/ritonavir. lowest possible dose of atorvastatin should be administered with careful safety monitoring (see section 4.4). Rosuvastatin, 20 mg QD Rosuvastatin: Caution should be exercised and AUC: ↑ 2-fold reduced doses should be Cmax: ↑ 5-fold considered when Kaletra is While rosuvastatin is poorly co-administered with rosuvastatin metabolised by CYP3A4, an (see section 4.4). increase of its plasma concentrations was observed. The mechanism of this interaction may result from inhibition of transport proteins. Fluvastatin or Pravastatin Fluvastatin, Pravastatin: If treatment with an HMG-CoA No clinical relevant interaction reductase inhibitor is indicated, expected. fluvastatin or pravastatin is Pravastatin is not metabolised by recommended. CYP450. Fluvastatin is partially metabolised by CYP2C9. Opioids Buprenorphine, 16 mg QD Buprenorphine: ↔ 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): atorvastatin (HOS-086304) lomitapide (HOS-086160) rosuvastatin (HOS-086307) fluvastatin (HOS-086305) buprenorphine (HOS-086193) pravastatin (HOS-086306)

Wechselwirkungen · Kaletra

Kaletra (80 mg + 20 mg) / ml oral solution · Abschnitt 4.5 · PDF-Seite 25–26

HOS-108940 · Präparat HOS-093083

Methadone Methadone: ↓ Monitoring plasma concentrations of methadone is recommended. Oral contraceptives Ethinyl Oestradiol Ethinyl Oestradiol: ↓ In case of co-administration of Kaletra with contraceptives containing ethinyl oestradiol (whatever the contraceptive formulation e.g. oral or patch), additional methods of contraception must be used. Smoking cessation aids Bupropion Buproprion and its active If the co-administration of Kaletra metabolite, hydroxybupropion: with bupropion is judged AUC and Cmax ↓ ~50% unavoidable, this should be done under close clinical monitoring for This effect may be due to bupropion efficacy, without induction of bupropion exceeding the recommended metabolism. dosage, despite the observed induction. Thyroid hormone replacement therapy Levothyroxine Post-marketing cases have been Thyroid-stimulating hormone reported indicating a potential (TSH) should be monitored in interaction between ritonavir patients treated with levothyroxine containing products and at least the first month after levothyroxine. starting and/or ending lopinavir/ritonavir treatment. Vasodilating agents 25  Bosentan Lopinavir - ritonavir: Caution should be exercised in Lopinavir/ritonavir plasma administering Kaletra with concentrations may decrease due bosentan. to CYP3A4 induction by When Kaletra is administered bosentan. concomitantly with bosentan, the efficacy of the HIV therapy should Bosentan: be monitored and patients should AUC: ↑ 5-fold be closely observed for bosentan Cmax: ↑ 6-fold toxicity, especially during the first Initially, bosentan Cmin: ↑ by week of co-administration. approximately 48-fold. Due to CYP3A4 inhibition by lopinavir/ritonavir. Riociguat Serum concentrations may be The co-administration of riociguat increased due to CYP3A and with Kaletra is not recommended P-gp inhibition by (see section 4.4 and refer to lopinavir/ritonavir. riociguat SmPC). Other medicinal products Based on known metabolic profiles, clinically significant interactions are not expected between Kaletra and dapsone, trimethoprim/sulfamethoxazole, azithromycin or fluconazole.

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): sulfamethoxazole (HOS-084533) bupropion (HOS-086329) riociguat (HOS-086293) methadone (HOS-086198) trimethoprim (HOS-085184) azithromycin (HOS-088112) fluconazole (HOS-087945) bosentan (HOS-086291) dapsone (HOS-088141) levothyroxine (HOS-086339)

Wechselwirkungen · Kaletra

Kaletra 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 47

HOS-108991 · 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 200 mg/50 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 47

HOS-108992 · 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.