Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Lojuxta

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HOS-127349 · Präparat HOS-096397

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. • Patients with moderate or severe hepatic impairment and those with unexplained persistent abnormal liver function tests (see section 4.2). • Patients with a known significant or chronic bowel disease such as inflammatory bowel disease or malabsorption. • Concomitant administration of > 40 mg simvastatin (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): simvastatin (HOS-086158)

Gegenanzeigen · Lojuxta

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HOS-127350 · Präparat HOS-096397

5 • Concomitant use of Lojuxta with strong or moderate CYP3A4 inhibitors (e.g. antifungal azoles such as itraconazole, fluconazole,ketoconazole, voriconazole, posaconazole; macrolide antibiotics such as erythromycin or clarithromycin; ketolide antibiotics such as telithromycin; human immunodeficiency virus (HIV) protease inhibitors; the calcium channel blockers diltiazem and verapamil, and the anti-arrhythmic dronedarone [see section 4.5]). • Pregnancy (see section 4.6).

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): diltiazem (HOS-086288) dronedarone (HOS-086144) protease (HOS-085623) ketoconazole (HOS-084513) calcium (HOS-085615) voriconazole (HOS-084524) telithromycin (HOS-084523) itraconazole (HOS-084516) fluconazole (HOS-087945) clarithromycin (HOS-084517) erythromycin (HOS-084514) posaconazole (HOS-085622) verapamil (HOS-090602)

Wechselwirkungen · Lojuxta

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HOS-127352 · Präparat HOS-096397

Effects of other medicinal products on lomitapide and other forms of interaction

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

Wechselwirkungen · Lojuxta

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HOS-127353 · Präparat HOS-096397

Table 3: Interactions between lomitapide and other medicinal products and other forms of interaction Medicinal Effects on lomitapide levels Recommendation concerning products co-administration with lomitapide Inhibitors of Strong and moderate inhibitors Strong and moderate inhibitors CYP3A4 When lomitapide 60 mg was Use of strong or moderate inhibitors of co-administered with ketoconazole CYP3A4 is contraindicated with Lojuxta. If 200 mg twice daily, a strong treatment with antifungal azoles (e.g. inhibitor of CYP3A4, lomitapide itraconazole, ketoconazole, fluconazole, area under the curve (AUC) voriconazole, posaconazole); the increased approximately 27-fold and antiarrhythmic dronedarone; macrolide maximum plasma concentration antibiotics (e.g. erythromycin, (Cmax) increased approximately clarithromycin); ketolide antibiotics (e.g. 15-fold. telithromycin); HIV protease inhibitors; the calcium channel blockers diltiazem and Interactions between moderate verapamil is unavoidable, therapy with CYP3A4 inhibitors and lomitapide Lojuxta should be suspended during the have not been studied. course of treatment (see sections 4.3 and 4.4). Moderate CYP3A4 inhibitors are predicted to have a substantial Grapefruit juice is a moderate inhibitor of impact on lomitapide CYP3A4 and is expected to substantially pharmacokinetics. Concomitant use increase exposure to lomitapide. Patients of moderate CYP3A4 inhibitors are taking Lojuxta should avoid consumption of expected to increase lomitapide grapefruit juice. exposure by 4-10 fold based on the results of the study with the strong CYP3A4 inhibitor ketoconazole and on historical data for the model CYP3A4 probe midazolam.

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): diltiazem (HOS-086288) dronedarone (HOS-086144) protease (HOS-085623) ketoconazole (HOS-084513) grapefruit juice (HOS-088787) calcium (HOS-085615) voriconazole (HOS-084524) telithromycin (HOS-084523) itraconazole (HOS-084516) fluconazole (HOS-087945) clarithromycin (HOS-084517) erythromycin (HOS-084514) posaconazole (HOS-085622) midazolam (HOS-086167) verapamil (HOS-090602)

Wechselwirkungen · Lojuxta

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HOS-127354 · Präparat HOS-096397

10  Medicinal Effects on lomitapide levels Recommendation concerning products co-administration with lomitapide Weak inhibitors Weak inhibitors

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

Wechselwirkungen · Lojuxta

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HOS-127355 · Präparat HOS-096397

Weak CYP3A4 inhibitors are When administered with atorvastatin, the expected to increase the exposure of dose of lomitapide should either be taken lomitapide when taken 12 hours apart or be decreased by half (see simultaneously. section 4.2). The dose of lomitapide should be taken 12 hours apart from any other When lomitapide 20 mg was concomitant weak CYP3A4 inhibitors. co-administered simultaneously with Examples of weak CYP3A4 inhibitors atorvastatin, a weak CYP3A4 include: alprazolam, amiodarone, inhibitor, lomitapide AUC and Cmax amlodipine, atorvastatin, azithromycin, increased approximately 2-fold. bicalutamide, cilostazol, cimetidine, When the dose of lomitapide was ciclosporin, clotrimazole, fluoxetine, taken 12 hours apart from fluvoxamine, fosaprepitant, ginkgo, atorvastatin, no clinically meaningful goldenseal, isoniazid, ivacaftor, lacidipine, increase in lomitapide exposure was lapatinib, linagliptin, nilotinib, observed. oestrogen-containing oral contraceptives, pazopanib, peppermint oil, propiverine, When lomitapide 20 mg was co- ranitidine, ranolazine, roxithromycin, Seville administered simultaneously or oranges, tacrolimus, ticagrelor and tolvaptan. 12 hours apart with ethinyl This list is not intended to be comprehensive estradiol/norgestimate, a weak and prescribers should check the prescribing CYP3A4 inhibitor, no clinically information of medicinal products to be co- meaningful increase in lomitapide administered with Lojuxta for potential exposure was observed. CYP3A4 mediated interactions.

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): ticagrelor (HOS-112065) lacidipine (HOS-113865) norgestimate (HOS-110544) cilostazol (HOS-111550) cimetidine (HOS-085835) atorvastatin (HOS-086304) alprazolam (HOS-086171) roxithromycin (HOS-127365) propiverine (HOS-127363) peppermint oil (HOS-127362) estradiol (HOS-090751) amlodipine (HOS-086287) azithromycin (HOS-088112) clotrimazole (HOS-090574) bicalutamide (HOS-127356) tolvaptan (HOS-109429) fosaprepitant (HOS-117427) lapatinib (HOS-122565) ivacaftor (HOS-109475) tacrolimus (HOS-085202) linagliptin (HOS-124309) pazopanib (HOS-122551) fluoxetine (HOS-085946) ranitidine (HOS-085660) amiodarone (HOS-085596) fluvoxamine (HOS-085908) ranolazine (HOS-086141) isoniazid (HOS-088590) nilotinib (HOS-086218)

Wechselwirkungen · Lojuxta

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HOS-127368 · Präparat HOS-096397

The effect of administration of more than one weak CYP3A4 inhibitor has not been tested, but the effect on the exposure of lomitapide is expected to be greater than for co-administration of the individual inhibitors with lomitapide.

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

Wechselwirkungen · Lojuxta

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HOS-127369 · Präparat HOS-096397

Exercise additional caution if administering more than 1 weak CYP3A4 inhibitor with Lojuxta.

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

Wechselwirkungen · Lojuxta

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HOS-127370 · Präparat HOS-096397

Inducers of Medicines that induce CYP3A4 When co-administering CYP3A4 inducers CYP3A4 would be expected to increase the (i.e. aminoglutethimide, nafcillin, rate and extent of metabolism of non-nucleoside reverse transcriptase lomitapide. Consequently, this inhibitors, phenobarbital, rifampicin, would reduce the effect of carbamazepine, pioglitazone, St John’s lomitapide. Any impact on efficacy Wort, glucocorticoids, modafinil and is likely to be variable. phenytoin) with Lojuxta, the possibility of a drug-drug interaction affecting efficacy should be considered. It is recommended to increase the frequency of LDL-C assessment during such concomitant use and consider increasing the dose of lomitapide to ensure maintenance of the desired level of efficacy if the CYP3A4 inducer is intended for chronic use.

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) modafinil (HOS-090546) carbamazepine (HOS-085618) aminoglutethimide (HOS-127371) nafcillin (HOS-125452) pioglitazone (HOS-089663) phenytoin (HOS-084531)

Wechselwirkungen · Lojuxta

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HOS-127372 · Präparat HOS-096397

11  Medicinal Effects on lomitapide levels Recommendation concerning products co-administration with lomitapide Bile acid Lomitapide has not been tested for Because bile acid sequestrants can interfere sequestrants interaction with bile acid with the absorption of oral medicines, bile sequestrants (resins such as acid sequestrants should be taken at least colesevelam and cholestyramine). 4 hours before or at least 4 hours after Lojuxta.

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): colesevelam (HOS-112356)

Wechselwirkungen · Lojuxta

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HOS-127374 · Präparat HOS-096397

Effects of lomitapide on other medicinal products

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

Wechselwirkungen · Lojuxta

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HOS-127375 · Präparat HOS-096397

HMG-CoA reductase inhibitors (“statins”) Lomitapide increases plasma concentrations of statins. When lomitapide 60 mg was administered to steady state prior to simvastatin 40 mg, simvastatin acid AUC and Cmax increased 68% and 57%, respectively. When lomitapide 60 mg was administered to steady state prior to atorvastatin 20 mg, atorvastatin acid AUC and Cmax increased 52% and 63%, respectively. When lomitapide 60 mg was administered to steady state prior to rosuvastatin 20 mg, rosuvastatin time to maximum concentration (Tmax) increased from 1 to 4 hours, AUC was increased 32%, and its Cmax was unchanged. The risk of myopathy with simvastatin is dose related. Use of Lojuxta is contraindicated in patients treated with high doses of simvastatin (> 40 mg) (see sections 4.3 and 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): atorvastatin (HOS-086304) simvastatin (HOS-086158) rosuvastatin (HOS-086307)

Wechselwirkungen · Lojuxta

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HOS-127376 · Präparat HOS-096397

Coumarin anticoagulants When lomitapide 60 mg was administered to steady state and 6 days following warfarin 10 mg, INR increased 1.26-fold. AUCs for R(+)-warfarin and S(-)-warfarin increased 25% and 30%, respectively. Cmax for R(+)-warfarin and S(-)-warfarin increased 14% and 15%, respectively. In patients taking coumarins (such as warfarin) and Lojuxta concomitantly, INR should be determined before starting Lojuxta and monitored regularly with dosage of coumarins adjusted as clinically indicated (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): coumarin (HOS-088372) warfarin (HOS-085950)

Wechselwirkungen · Lojuxta

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HOS-127377 · Präparat HOS-096397

Fenofibrate, niacin and ezetimibe When lomitapide was administered to steady state prior to micronised fenofibrate 145 mg, extended release niacin 1 000 mg, or ezetimibe 10 mg, no clinically significant effects on the exposure of any of these medicinal products were observed. No dose adjustments are required when co-administered with Lojuxta.

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): fenofibrate (HOS-123816) niacin (HOS-126975) ezetimibe (HOS-127378)

Wechselwirkungen · Lojuxta

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HOS-127379 · Präparat HOS-096397

Oral contraceptives When lomitapide 50 mg was administered to steady state along with an oestrogen-based oral contraceptive, no clinically meaningful or statistically significant impact on the pharmacokinetics of the components of the oral contraceptive (ethinyl estradiol and 17-deacetyl norgestimate, the metabolite of norgestimate) was observed. Lomitapide is not expected to directly influence the efficacy of oestrogen based oral contraceptives; however diarrhoea and/or vomiting may reduce hormone absorption. In cases of protracted or severe diarrhoea and/or vomiting lasting more than 2 days, additional contraceptive measures should be used for 7 days after resolution of symptoms.

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): norgestimate (HOS-110544) ethinyl estradiol (HOS-088135)

Wechselwirkungen · Lojuxta

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HOS-127380 · Präparat HOS-096397

P-glycoprotein (P-gp) substrates Lomitapide inhibits P-gp in vitro, and may increase the absorption of P-gp substrates. Coadministration of Lojuxta with P-gp substrates (such as aliskiren, ambrisentan, colchicine, dabigatran etexilate, digoxin, everolimus, fexofenadine, imatinib, lapatinib, maraviroc, nilotinib, posaconazole, ranolazine, saxagliptin, sirolimus, sitagliptin, talinolol, tolvaptan, topotecan) may increase the absorption of P-gp substrates. Dose reduction of the P-gp substrate should be considered when used concomitantly with Lojuxta.

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): fexofenadine (HOS-086255) saxagliptin (HOS-121455) talinolol (HOS-127384) ambrisentan (HOS-114927) digoxin (HOS-086172) aliskiren (HOS-086927) tolvaptan (HOS-109429) imatinib (HOS-110212) lapatinib (HOS-122565) maraviroc (HOS-086186) colchicine (HOS-086147) everolimus (HOS-086310) sirolimus (HOS-085172) topotecan (HOS-086047) ranolazine (HOS-086141) sitagliptin (HOS-117222) dabigatran etexilate (HOS-086233) posaconazole (HOS-085622) nilotinib (HOS-086218)

Wechselwirkungen · Lojuxta

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HOS-127385 · Präparat HOS-096397

In vitro assessment of drug interactions Lomitapide inhibits CYP3A4. Lomitapide does not induce CYPs 1A2, 3A4, or 2B6, and does not inhibit CYPs 1A2, 2B6, 2C9, 2C19, 2D6, or 2E1. Lomitapide is not a P-gp substrate but does inhibit P-gp. Lomitapide does not inhibit breast cancer resistance protein (BCRP).

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

Nebenwirkungen · Lojuxta

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HOS-127386 · Präparat HOS-096397

Summary of the safety profile

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

Nebenwirkungen · Lojuxta

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HOS-127387 · Präparat HOS-096397

The most serious adverse reactions during treatment were liver aminotransferase abnormalities (see section 4.4).

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

Nebenwirkungen · Lojuxta

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HOS-127388 · Präparat HOS-096397

The most common adverse reactions in adults are gastrointestinal effects (93%) i.e. diarrhoea (79%), nausea (65%), dyspepsia (38%), and vomiting (34%). Other reactions reported by at least 20% of patients include abdominal pain, abdominal discomfort, abdominal distension, constipation, and flatulence. Gastrointestinal adverse reactions occurred more frequently during the dose escalation phase of the study and decreased once patients established the maximum tolerated dose of lomitapide.

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