Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 11–12

HOS-115540 · Präparat HOS-094307

11 Interaction with repaglinide and other agents metabolised by CYP2C8 In a healthy volunteer study, the concomitant administration of deferasirox as a moderate CYP2C8 inhibitor (30 mg/kg daily, dispersible tablet formulation), with repaglinide, a CYP2C8 substrate, given as a single dose of 0.5 mg, increased repaglinide AUC and Cmax about 2.3-fold (90% CI [2.03-2.63]) and 1.6-fold (90% CI [1.42-1.84]), respectively. Since the interaction has not been established with dosages higher than 0.5 mg for repaglinide, the concomitant use of deferasirox with repaglinide should be avoided. If the combination appears necessary, careful clinical and blood glucose monitoring should be performed (see section 4.4). An interaction between deferasirox and other CYP2C8 substrates like paclitaxel cannot be excluded.

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): glucose (HOS-088412) paclitaxel (HOS-087959) repaglinide (HOS-086935)

Wechselwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12

HOS-115544 · Präparat HOS-094307

Interaction with theophylline and other agents metabolised by CYP1A2 In a healthy volunteer study, the concomitant administration of deferasirox as a CYP1A2 inhibitor (repeated dose of 30 mg/kg/day, dispersible tablet formulation) and the CYP1A2 substrate theophylline (single dose of 120 mg) resulted in an increase of theophylline AUC by 84% (90% CI: 73% to 95%). The single dose Cmax was not affected, but an increase of theophylline Cmax is expected to occur with chronic dosing. Therefore, the concomitant use of deferasirox with theophylline is not recommended. If deferasirox and theophylline are used concomitantly, monitoring of theophylline concentration and theophylline dose reduction should be considered. An interaction between deferasirox and other CYP1A2 substrates cannot be excluded. For substances that are predominantly metabolised by CYP1A2 and that have a narrow therapeutic index (e.g. clozapine, tizanidine), the same recommendations apply as for theophylline.

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): tizanidine (HOS-089668) theophylline (HOS-085910) clozapine (HOS-086149)

Wechselwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12

HOS-115549 · Präparat HOS-094307

Other information The concomitant administration of deferasirox and aluminium-containing antacid preparations has not been formally studied. Although deferasirox has a lower affinity for aluminium than for iron, it is not recommended to take deferasirox tablets with aluminium-containing antacid preparations.

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): iron (HOS-085656)

Wechselwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12

HOS-115551 · Präparat HOS-094307

The concomitant administration of deferasirox with substances that have known ulcerogenic potential, such as NSAIDs (including acetylsalicylic acid at high dosage), corticosteroids or oral bisphosphonates may increase the risk of gastrointestinal toxicity (see section 4.4). The concomitant administration of deferasirox with anticoagulants may also increase the risk of gastrointestinal haemorrhage. Close clinical monitoring is required when deferasirox is combined with these substances.

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

Wechselwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12

HOS-115552 · Präparat HOS-094307

Concomitant administration of deferasirox and busulfan resulted in an increase of busulfan exposure (AUC), but the mechanism of the interaction remains unclear. If possible, evaluation of the pharmacokinetics (AUC, clearance) of a busulfan test dose should be performed to allow dose adjustment.

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): busulfan (HOS-115553)

Wechselwirkungen · Exjade

EXJADE 90 mg granules in sachet EXJADE 180 mg granules in sachet EXJADE 360 mg granules in sachet · Abschnitt 4.5 · PDF-Seite 31

HOS-115570 · Präparat HOS-094307

Interaction with food There were no clinically relevant changes in deferasirox pharmacokinetics when EXJADE granules were administered with food. Although there was no significant effect (increase in the extent of absorption AUC by 18-19%; no change in Cmax) of a high-fat meal on deferasirox pharmacokinetics, it is recommended that deferasirox granules be taken either with or without a light meal (see section 5.2).

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

Wechselwirkungen · Exjade

EXJADE 90 mg granules in sachet EXJADE 180 mg granules in sachet EXJADE 360 mg granules in sachet · Abschnitt 4.5 · PDF-Seite 31

HOS-115571 · Präparat HOS-094307

Agents that may decrease EXJADE systemic exposure Deferasirox metabolism depends on UGT enzymes. In a healthy volunteer study, the concomitant administration of deferasirox (single dose of 30 mg/kg, dispersible tablet formulation) and the potent UGT inducer, rifampicin, (repeated dose of 600 mg/day) resulted in a decrease of deferasirox exposure by 44% (90% CI: 37% - 51%). Therefore, the concomitant use of EXJADE with potent UGT inducers (e.g. rifampicin, carbamazepine, phenytoin, phenobarbital, ritonavir) may result in a decrease in EXJADE efficacy. The patient’s serum ferritin should be monitored during and after the combination, and the dose of EXJADE adjusted if 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): phenobarbital (HOS-085617) carbamazepine (HOS-085618) ritonavir (HOS-084521) phenytoin (HOS-084531)

Wechselwirkungen · Exjade

EXJADE 90 mg granules in sachet EXJADE 180 mg granules in sachet EXJADE 360 mg granules in sachet · Abschnitt 4.5 · PDF-Seite 31

HOS-115572 · Präparat HOS-094307

Cholestyramine significantly reduced the deferasirox exposure in a mechanistic study to determine the degree of enterohepatic recycling (see section 5.2).

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

Wechselwirkungen · Exjade

EXJADE 90 mg granules in sachet EXJADE 180 mg granules in sachet EXJADE 360 mg granules in sachet · Abschnitt 4.5 · PDF-Seite 31

HOS-115573 · Präparat HOS-094307

Interaction with midazolam and other agents metabolised by CYP3A4 In a healthy volunteer study, the concomitant administration of deferasirox dispersible tablets and midazolam (a CYP3A4 probe substrate) resulted in a decrease of midazolam exposure by 17% (90% CI: 8% - 26%). In the clinical setting, this effect may be more pronounced. Therefore, due to a possible decrease in efficacy, caution should be exercised when deferasirox is combined with substances metabolised through CYP3A4 (e.g. ciclosporin, simvastatin, hormonal contraceptive agents, bepridil, ergotamine).

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): bepridil (HOS-085612) simvastatin (HOS-086158) ergotamine (HOS-086154) midazolam (HOS-086167)

Wechselwirkungen · Exjade

EXJADE 90 mg granules in sachet EXJADE 180 mg granules in sachet EXJADE 360 mg granules in sachet · Abschnitt 4.5 · PDF-Seite 31–32

HOS-115574 · Präparat HOS-094307

31 Interaction with repaglinide and other agents metabolised by CYP2C8 In a healthy volunteer study, the concomitant administration of deferasirox as a moderate CYP2C8 inhibitor (30 mg/kg daily, dispersible tablet formulation), with repaglinide, a CYP2C8 substrate, given as a single dose of 0.5 mg, increased repaglinide AUC and Cmax about 2.3-fold (90% CI [2.03-2.63]) and 1.6-fold (90% CI [1.42-1.84]), respectively. Since the interaction has not been established with dosages higher than 0.5 mg for repaglinide, the concomitant use of deferasirox with repaglinide should be avoided. If the combination appears necessary, careful clinical and blood glucose monitoring should be performed (see section 4.4). An interaction between deferasirox and other CYP2C8 substrates like paclitaxel cannot be excluded.

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): glucose (HOS-088412) paclitaxel (HOS-087959) repaglinide (HOS-086935)

Wechselwirkungen · Exjade

EXJADE 90 mg granules in sachet EXJADE 180 mg granules in sachet EXJADE 360 mg granules in sachet · Abschnitt 4.5 · PDF-Seite 32

HOS-115575 · Präparat HOS-094307

Interaction with theophylline and other agents metabolised by CYP1A2 In a healthy volunteer study, the concomitant administration of deferasirox as a CYP1A2 inhibitor (repeated dose of 30 mg/kg/day, dispersible tablet formulation) and the CYP1A2 substrate theophylline (single dose of 120 mg) resulted in an increase of theophylline AUC by 84% (90% CI: 73% to 95%). The single dose Cmax was not affected, but an increase of theophylline Cmax is expected to occur with chronic dosing. Therefore, the concomitant use of deferasirox with theophylline is not recommended. If deferasirox and theophylline are used concomitantly, monitoring of theophylline concentration and theophylline dose reduction should be considered. An interaction between deferasirox and other CYP1A2 substrates cannot be excluded. For substances that are predominantly metabolised by CYP1A2 and that have a narrow therapeutic index (e.g. clozapine, tizanidine), the same recommendations apply as for theophylline.

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): tizanidine (HOS-089668) theophylline (HOS-085910) clozapine (HOS-086149)

Wechselwirkungen · Exjade

EXJADE 90 mg granules in sachet EXJADE 180 mg granules in sachet EXJADE 360 mg granules in sachet · Abschnitt 4.5 · PDF-Seite 32

HOS-115578 · Präparat HOS-094307

Other information The concomitant administration of deferasirox and aluminium-containing antacid preparations has not been formally studied. Although deferasirox has a lower affinity for aluminium than for iron, it is not recommended to take deferasirox granules with aluminium-containing antacid preparations.

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): iron (HOS-085656)

Wechselwirkungen · Exjade

EXJADE 90 mg granules in sachet EXJADE 180 mg granules in sachet EXJADE 360 mg granules in sachet · Abschnitt 4.5 · PDF-Seite 32

HOS-115579 · Präparat HOS-094307

The concomitant administration of deferasirox with substances that have known ulcerogenic potential, such as NSAIDs (including acetylsalicylic acid at high dosage), corticosteroids or oral bisphosphonates may increase the risk of gastrointestinal toxicity (see section 4.4). The concomitant administration of deferasirox with anticoagulants may also increase the risk of gastrointestinal haemorrhage. Close clinical monitoring is required when deferasirox is combined with these substances.

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

Wechselwirkungen · Exjade

EXJADE 90 mg granules in sachet EXJADE 180 mg granules in sachet EXJADE 360 mg granules in sachet · Abschnitt 4.5 · PDF-Seite 32

HOS-115580 · Präparat HOS-094307

Concomitant administration of deferasirox and busulfan resulted in an increase of busulfan exposure (AUC), but the mechanism of the interaction remains unclear. If possible, evaluation of the pharmacokinetics (AUC, clearance) of a busulfan test dose should be performed to allow dose adjustment.

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): busulfan (HOS-115553)

Nebenwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-115554 · Präparat HOS-094307

Summary of the safety profile The most frequent reactions reported during chronic treatment in clinical studies conducted with deferasirox dispersible tablets in adult and paediatric patients include gastrointestinal disturbances (mainly nausea, vomiting, diarrhoea or abdominal pain) and skin rash. Diarrhoea is reported more commonly in paediatric patients aged 2 to 5 years and in the elderly. These reactions are dose- dependent, mostly mild to moderate, generally transient and mostly resolve even if treatment is continued.

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

Nebenwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-115555 · Präparat HOS-094307

During clinical studies dose-dependent increases in serum creatinine occurred in about 36% of patients, though most remained within the normal range. Decreases in mean creatinine clearance have been observed in both paediatric and adult patients with beta-thalassemia and iron overload during the first year of treatment, but there is evidence that this does not decrease further in subsequent years of treatment. Elevations of liver transaminases have been reported. Safety monitoring schedules for renal and liver parameters are recommended. Auditory (decreased hearing) and ocular (lens opacities) disturbances are uncommon, and yearly examinations are also recommended (see section 4.4).

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

Nebenwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-115556 · Präparat HOS-094307

Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with the use of EXJADE (see section 4.4).

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

Nebenwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13

HOS-115557 · Präparat HOS-094307

Tabulated list of adverse reactions Adverse reactions are ranked below using the following convention: 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); not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

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

Nebenwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 13–14

HOS-115558 · Präparat HOS-094307

13 Table 6

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

Nebenwirkungen · Exjade

EXJADE 90 mg film-coated tablets EXJADE 180 mg film-coated tablets EXJADE 360 mg film-coated tablets · Abschnitt 4.8 · PDF-Seite 14

HOS-115559 · Präparat HOS-094307

Blood and lymphatic system disorders Not known: Pancytopenia1, thrombocytopenia1, anaemia aggravated1, neutropenia1 Immune system disorders Not known: Hypersensitivity reactions (including anaphylactic reactions and angioedema)1 Metabolism and nutrition disorders Not known: Metabolic acidosis1 Psychiatric disorders Uncommon: Anxiety, sleep disorder Nervous system disorders Common: Headache Uncommon: Dizziness Eye disorders Uncommon: Cataract, maculopathy Rare: Optic neuritis Ear and labyrinth disorders Uncommon: Deafness Respiratory, thoracic and mediastinal disorders Uncommon: Laryngeal pain Gastrointestinal disorders Common: Diarrhoea, constipation, vomiting, nausea, abdominal pain, abdominal distension, dyspepsia Uncommon: Gastrointestinal haemorrhage, gastric ulcer (including multiple ulcers), duodenal ulcer, gastritis Rare: Oesophagitis Not known: Gastrointestinal perforation1, acute pancreatitis1 Hepatobiliary disorders Common: Transaminases increased Uncommon: Hepatitis, cholelithiasis Not known: Hepatic failure1, 2 Skin and subcutaneous tissue disorders Common: Rash, pruritus Uncommon: Pigmentation disorder Rare: Drug reaction with eosinophilia and systemic symptoms (DRESS) Not known: Stevens-Johnson syndrome1, hypersensitivity vasculitis1, urticaria1, erythema multiforme1, alopecia1, toxic epidermal necrolysis (TEN)1 Renal and urinary disorders Very common: Blood creatinine increased Common: Proteinuria Uncommon: Renal tubular disorder2 (acquired Fanconi syndrome), glycosuria Not known: Acute renal failure1, 2, tubulointerstitial nephritis1, nephrolithiasis1, renal tubular necrosis1 General disorders and administration site conditions Uncommon: Pyrexia, oedema, fatigue 1 Adverse reactions reported during post-marketing experience. These are derived from spontaneous reports for which it is not always possible to reliably establish frequency or a causal relationship to exposure to the medicinal product. 2 Severe forms associated with changes in consciousness in the context of hyperammonaemic encephalopathy have been reported.

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