Wirkstoffe & Arzneimittelsicherheit

Nebenwirkungen · Pravafenix

Pravafenix 40 mg/160 mg hard capsules · Abschnitt 4.8 · PDF-Seite 8

HOS-123837 · Präparat HOS-095735

Summary of the safety profile The most commonly reported adverse reactions (ADRs) during Pravafenix therapy are increased transaminase and gastrointestinal disorders.

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

Nebenwirkungen · Pravafenix

Pravafenix 40 mg/160 mg hard capsules · Abschnitt 4.8 · PDF-Seite 8

HOS-123838 · Präparat HOS-095735

Tabulated list of adverse reactions In clinical trials, over 1,566 patients received Pravafenix. Adverse reactions have usually been mild and transient.

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

Nebenwirkungen · Pravafenix

Pravafenix 40 mg/160 mg hard capsules · Abschnitt 4.8 · PDF-Seite 8

HOS-123839 · Präparat HOS-095735

The frequencies of adverse reactions are ranked according to the following: Very common (≥ 1/10), Common (≥ 1/100 to < 1/10), Uncommon (≥ 1/1,000 to < 1/100), Rare (≥ 1/10,000 to < 1/1,000), Very rare (< 1/10,000).

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

Nebenwirkungen · Pravafenix

Pravafenix 40 mg/160 mg hard capsules · Abschnitt 4.8 · PDF-Seite 8

HOS-123840 · Präparat HOS-095735

System organ class Adverse reaction Frequency Immune system Hypersensitivity reactions Uncommon disorders Metabolism and Diabetes mellitus aggravated, Obesity Uncommon nutrition disorders Psychiatric disorders Sleep disturbance including insomnia and nightmares Uncommon Nervous system Dizziness, headache, paraesthesia Uncommon disorders Cardiac disorders Palpitations Uncommon Gastrointestinal Abdominal distension, abdominal pain, abdominal pain upper, Common disorders constipation, diarrhoea, dry mouth, dyspepsia, eructation, flatulence, nausea, abdominal discomfort, vomiting. Hepatobiliary disorders Transaminases increased. Common Hepatic pain, gammaglutamyl transferase increased. Uncommon Skin and subcutaneous Pruritus, urticaria Uncommon tissue disorders

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

Nebenwirkungen · Pravafenix

Pravafenix 40 mg/160 mg hard capsules · Abschnitt 4.8 · PDF-Seite 8–9

HOS-123841 · Präparat HOS-095735

8  Arthralgia, back pain, blood creatine phosphokinase increased, Uncommon Musculoskeletal, muscle spasms, musculoskeletal pain, myalgia, pain in extremity. connective tissue and bone disorders

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

Nebenwirkungen · Pravafenix

Pravafenix 40 mg/160 mg hard capsules · Abschnitt 4.8 · PDF-Seite 9

HOS-123842 · Präparat HOS-095735

Renal and urinary Blood creatinine increased, creatinine renal clearance decreased, Uncommon disorders creatinine renal clearance increased, Renal failure General disorders and Asthenia, fatigue, influenza like illness Uncommon administration site conditions Investigation Blood cholesterol increased, blood triglycerides increased, low- Uncommon density lipoprotein increased, weight increased.

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

Nebenwirkungen · Pravafenix

Pravafenix 40 mg/160 mg hard capsules · Abschnitt 4.8 · PDF-Seite 9

HOS-123843 · Präparat HOS-095735

Description of selected adverse reactions

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

Nebenwirkungen · Pravafenix

Pravafenix 40 mg/160 mg hard capsules · Abschnitt 4.8 · PDF-Seite 9

HOS-123844 · Präparat HOS-095735

Skeletal muscle: Marked and persistent increases of creatine phosphokinase (CK) have been reported infrequently. In clinical studies, the incidence of important elevations in creatine phosphokinase (CK ≥ 3 times the ULN, < 5 times the ULN) was 1.92% for patients treated with Pravafenix. Clinically important elevations in creatine phosphokinase (CK ≥ 5 times the ULN, < 10 times the ULN without muscular symptoms) were seen in 0.38% of the patients treated with Pravafenix. Clinically important elevation (CK ≥ 10 times the ULN without muscular symptoms) was seen in 0.06% of the patients treated with Pravafenix. (see section 4.4).

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

Nebenwirkungen · Pravafenix

Pravafenix 40 mg/160 mg hard capsules · Abschnitt 4.8 · PDF-Seite 9

HOS-123845 · Präparat HOS-095735

Liver reactions: Marked and persistent increases of serum transaminases have been reported infrequently. In clinical studies, the incidence of important elevations in serum transaminases (ALT and/or AST ≥ 3 times the ULN, < 5 times the ULN) was 0.83% for patients treated with Pravafenix. Clinically important elevations in serum transaminases (ALT and/or AST ≥ 5 times the ULN) were seen in 0.38% of the patients treated with Pravafenix. (see section 4.4).

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

Nebenwirkungen · Pravafenix

Pravafenix 40 mg/160 mg hard capsules · Abschnitt 4.8 · PDF-Seite 9

HOS-123846 · Präparat HOS-095735

Additional information on the individual active substances of the fixed dose combination Pravafenix contains pravastatin and fenofibrate. Additional adverse reactions associated with the use of medicinal products containing pravastatin or fenofibrate observed in clinical trials and post- marketing experience that may potentially occur with Pravafenix are listed below. Frequency categories are based on information available from pravastatin and fenofibrate Summary of Product characteristics available in the EU.

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

Nebenwirkungen · Pravafenix

Pravafenix 40 mg/160 mg hard capsules · Abschnitt 4.8 · PDF-Seite 9–10

HOS-123847 · Präparat HOS-095735

System Organ Class Adverse reaction Adverse reaction Frequency (fenofibrate) (Pravastatin) Blood and lymphatic Haemoglobin decreased, Rare system disorders White blood cell count decreased Nervous system Fatigue and vertigo Rare disorders Peripheral polyneuropathy Very Rare Myasthenia gravis Not known Eye disorders Vision disturbance (including Uncommon blurred vision and diplopia) Ocular myasthenia Not known Vascular disorders Thromboembolism Uncommon (pulmonary embolism, deep vein thrombosis)* Respiratory, thoracic Intersticial pneumopathies Not known and mediastinal disorders Hepatobiliary disorders Cholelithiasis Uncommon 9  Jaundice, fulminant hepatic Very rare necrosis, hepatitis Jaundice, complications of Not known cholelithiasis (e.g cholecystitis, cholangitis, biliary colic, etc). Skin and subcutaneous Skin rash, Scalp/hair abnormality Uncommon tissue disorders (including alopecia) Dermatomyositis Very rare Alopecia, photosensitivity Rare reactions Lichenoid eruption Not known Musculoskeletal, Muscle disorder (e.g. Uncommon connective tissue and myositis, muscular bone disorders weakness) Muscle rupture Not known Rhabdomyolysis, which can be Very rare associated with acute renal failure secondary to myoglobinuria, myopathy (see section 4.4); myositis, polymyositis. Isolated cases of tendon disorders, sometimes complicated by rupture. Erythematous lupus like syndrome. Rhabdomyolysis Immune-mediated necrotizing Not known myopathy (see section 4.4). Renal and urinary Abnormal urination (including Uncommon disorders: dysuria, frequency, nocturia) Reproductive system Sexual dysfunction Sexual dysfunction Uncommon and breast disorders General disorders: Fatigue Uncommon Investigations Blood urea increased Rare * In the FIELD-study (fenofibrate study), a randomised placebo-controlled trial performed in 9,795 patients with type 2 diabetes mellitus, a statistically significant increase in pancreatitis cases was observed in patients receiving fenofibrate versus patients receiving placebo (0.8% versus 0.5%; p = 0.031). In the same study, a statistically significant increase was reported in the incidence of pulmonary embolism (0.7% in the placebo group versus 1.1% in the fenofibrate group; p = 0.022) and a statistically non-significant increase in deep vein thromboses (placebo: 1.0 % [48/4,900 patients] versus fenofibrate 1.4% [67/4,895 patients]; p = 0.074).

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

Nebenwirkungen · Pravafenix

Pravafenix 40 mg/160 mg hard capsules · Abschnitt 4.8 · PDF-Seite 10

HOS-123848 · Präparat HOS-095735

The following adverse events have been reported with some statins: - Nightmares - Memory loss - Depression - Exceptional cases of interstitial lung disease, especially with long term therapy (see section 4.4). - Diabetes Mellitus: Frequency will depend on the presence or absence of risk factors (fasting blood glucose ≥ 5.6 mmol/L, BMI>30kg/m2, raised triglycerides, history of hypertension).

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

Nebenwirkungen · Pravafenix

Pravafenix 40 mg/160 mg hard capsules · Abschnitt 4.8 · PDF-Seite 10

HOS-123849 · Präparat HOS-095735

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

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

Wechselwirkungen · Leflunomide ratiopharm

Leflunomide ratiopharm 10 mg film-coated tablets Leflunomide ratiopharm 20 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-213336 · Präparat HOS-155090

Effect on BCRP (Breast Cancer Resistance Protein) and /or organic anion transporting polypeptide B1 and B3 (OATP1B1/B3) substrates There was an increase in mean rosuvastatin Cmax and AUC (2.65- and 2.51-fold, respectively), following repeated doses of A771726. However, there was no apparent impact of this increase in plasma rosuvastatin exposure on the HMG-CoA reductase activity. If used together, the dose of rosuvastatin should not exceed 10 mg once daily. For other substrates of BCRP (e.g., methotrexate, topotecan, sulfasalazine, daunorubicin, doxorubicin) and the OATP family especially HMG-CoA reductase inhibitors (e.g., simvastatin, atorvastatin, pravastatin, methotrexate, nateglinide, repaglinide, rifampicin) concomitant administration should also be undertaken with caution. Patients should be closely monitored for signs and symptoms of excessive exposure to the medicinal products and reduction of the dose of these medicinal products should be considered.

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): daunorubicin (HOS-089674) sulfasalazine (HOS-089673) atorvastatin (HOS-086304) simvastatin (HOS-086158) rosuvastatin (HOS-086307) nateglinide (HOS-089675) topotecan (HOS-086047) doxorubicin (HOS-084538) repaglinide (HOS-086935) pravastatin (HOS-086306) methotrexate (HOS-087522)

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 17

HOS-215313 · Präparat HOS-155418

Total active HMG CoA reductase inhibitors: AUC: ↓ 34% (↓ 21 to ↓ 41) Cmax: ↓ 20% (↓ 2 to ↓ 26) Pravastatin/efavirenz Pravastatin: Cholesterol levels should be (40 mg once daily/600 mg once AUC: ↓ 40% (↓ 26 to ↓ 57) periodically monitored. Dose daily) Cmax: ↓ 18% (↓ 59 to ↑ 12) adjustment of pravastatin may be required (refer to the Summary of Product Characteristics for pravastatin). No dose adjustment is necessary for efavirenz. Simvastatin/efavirenz Simvastatin: Cholesterol levels should be (40 mg once daily/600 mg once AUC: ↓ 69% (↓ 62 to ↓ 73) periodically monitored. Dose daily) Cmax: ↓ 76% (↓ 63 to ↓ 79) adjustment of simvastatin may be required (refer to the Summary of Simvastatin acid: Product Characteristics for AUC: ↓ 58% (↓ 39 to ↓ 68) simvastatin). No dose adjustment Cmax: ↓ 51% (↓ 32 to ↓ 58) is necessary for efavirenz.

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) cholesterol (HOS-087961) pravastatin (HOS-086306)

Wechselwirkungen · Efavirenz Teva

Efavirenz Teva 600 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 18

HOS-215316 · Präparat HOS-155418

(CYP3A4 induction) Co-administration of efavirenz with atorvastatin, pravastatin, or simvastatin did not affect efavirenz AUC or Cmax values. Rosuvastatin/efavirenz Interaction not studied. Rosuvastatin No dose adjustment is necessary is largely excreted unchanged via the for either medicinal product. faeces, therefore interaction with efavirenz is not expected. HORMONAL CONTRACEPTIVES Oral: Ethinyloestradiol: A reliable method of barrier Ethinyloestradiol + norgestimate / AUC: ↔ contraception must be used in efavirenz Cmax: ↔ addition to hormonal (0.035 mg + 0.25 mg once Cmin: ↓ 8% (↑ 14 to ↓ 25) contraceptives (see section 4.6). daily/600 mg once daily) Norelgestromin (active metabolite): AUC: ↓ 64% (↓ 62 to ↓ 67) Cmax: ↓ 46% (↓ 39 to ↓ 52) Cmin: ↓ 82% (↓ 79 to ↓ 85)

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) atorvastatin (HOS-086304) norelgestromin (HOS-110295) simvastatin (HOS-086158) rosuvastatin (HOS-086307) pravastatin (HOS-086306)

Wechselwirkungen · Xadago

Xadago 50 mg film-coated tablets Xadago 100 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 5

HOS-125742 · Präparat HOS-096139

Safinamide may transiently inhibit BCRP in vitro. In drug-drug-interaction studies in human, a weak interaction was observed with rosuvastatin (AUC increase between 1.25 and 2.00 fold) but no significant interaction was found with diclofenac. It is recommended to monitor patients when safinamide is taken with medicinal products that are BCRP substrates (e.g., rosuvastatin, pitavastatin, pravastatin, ciprofloxacin, methotrexate, topotecan, diclofenac or glyburide) and to refer to their SmPCs to determine if a dose adjustment is needed.

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): diclofenac (HOS-085903) ciprofloxacin (HOS-085177) rosuvastatin (HOS-086307) glyburide (HOS-109273) topotecan (HOS-086047) pravastatin (HOS-086306) methotrexate (HOS-087522) pitavastatin (HOS-125743)

Wechselwirkungen · Xalkori

XALKORI 200 mg hard capsules XALKORI 250 mg hard capsules XALKORI 20 mg granules in capsules for opening XALKORI 50 mg granules in capsules for opening XALKORI 150 mg granules in capsules for opening · Abschnitt 4.5 · PDF-Seite 16

HOS-126287 · Präparat HOS-096239

Based on an in vitro study, crizotinib is predicted to inhibit intestinal P-gp. Therefore, administration of crizotinib with medicinal products that are substrates of P-gp (e.g., digoxin, dabigatran, colchicine, pravastatin) may increase their therapeutic effect and adverse reactions. Close clinical surveillance is recommended when crizotinib is administered with these medicinal products.

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): digoxin (HOS-086172) dabigatran (HOS-112096) colchicine (HOS-086147) pravastatin (HOS-086306)

Wechselwirkungen · Aubagio

AUBAGIO 7 mg film-coated tablets AUBAGIO 14 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 8–9

HOS-126673 · Präparat HOS-096301

8 There was an increase in mean rosuvastatin Cmax and AUC (2.65- and 2.51-fold, respectively), following repeated doses of teriflunomide. However, there was no apparent impact of this increase in plasma rosuvastatin exposure on the HMG-CoA reductase activity. For rosuvastatin, a dose reduction by 50% is recommended for coadministration with teriflunomide. For other substrates of BCRP (e.g., methotrexate, topotecan, sulfasalazine, daunorubicin, doxorubicin) and the OATP family especially HMG-Co reductase inhibitors (e.g., simvastatin, atorvastatin, pravastatin, methotrexate, nateglinide, repaglinide, rifampicin) concomitant administration of teriflunomide should also be undertaken with caution. Patients should be closely monitored for signs and symptoms of excessive exposure to the medicinal products and reduction of the dose of these medicinal products should be considered.

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): daunorubicin (HOS-089674) sulfasalazine (HOS-089673) atorvastatin (HOS-086304) simvastatin (HOS-086158) rosuvastatin (HOS-086307) nateglinide (HOS-089675) topotecan (HOS-086047) doxorubicin (HOS-084538) repaglinide (HOS-086935) pravastatin (HOS-086306) methotrexate (HOS-087522)

Wechselwirkungen · Iclusig

Iclusig 15 mg film-coated tablets Iclusig 30 mg film-coated tablets Iclusig 45 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 16

HOS-128512 · Präparat HOS-096579

Transporter substrates In vitro, ponatinib is an inhibitor of P-gp and BCRP. Therefore, ponatinib may have the potential to increase plasma concentrations of co-administered substrates of P-gp (e.g., digoxin, dabigatran, colchicine, pravastatin) or BCRP (e.g., methotrexate, rosuvastatin, sulfasalazine) and may increase their therapeutic effect and adverse reactions. Close clinical surveillance is recommended when ponatinib is administered with these medicinal products.

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): sulfasalazine (HOS-089673) rosuvastatin (HOS-086307) digoxin (HOS-086172) dabigatran (HOS-112096) colchicine (HOS-086147) pravastatin (HOS-086306) methotrexate (HOS-087522)