Wirkstoffe & Arzneimittelsicherheit

Wechselwirkungen · Eurartesim

Eurartesim 160 mg/20 mg film-coated tablets. · Abschnitt 4.5 · PDF-Seite 7

HOS-123036 · Präparat HOS-095623

Food interaction Absorption of piperaquine is increased in the presence of fatty food (see sections 4.4 and 5.2) which may increase its effect on QTc interval. Therefore, Eurartesim should be taken with water only as described in section 4.2. Eurartesim should not be taken with grapefruit juice as it is likely to lead to increased piperaquine plasma 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): grapefruit juice (HOS-088787) lead (HOS-085592) water (HOS-114523)

Wechselwirkungen · Eurartesim

Eurartesim 320 mg/40 mg film-coated tablets. · Abschnitt 4.5 · PDF-Seite 21

HOS-123065 · Präparat HOS-095623

Eurartesim is contraindicated in patients already taking other medicinal products that are known to prolong the QTc interval due to the risk of a pharmacodynamic interaction leading to an additive effect on the QTc interval (see section 4.3 and 4.4).

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

Wechselwirkungen · Eurartesim

Eurartesim 320 mg/40 mg film-coated tablets. · Abschnitt 4.5 · PDF-Seite 21

HOS-123066 · Präparat HOS-095623

A limited number of drug-drug pharmacokinetic interaction studies with Eurartesim have been performed in healthy adult subjects. Therefore the assessment of the potential for drug-drug interactions to occur is based on either in vivo or in vitro studies.

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

Wechselwirkungen · Eurartesim

Eurartesim 320 mg/40 mg film-coated tablets. · Abschnitt 4.5 · PDF-Seite 21–22

HOS-123067 · Präparat HOS-095623

Effect of Eurartesim on co-administered medicinal products Piperaquine is metabolised by, and is an inhibitor of CYP3A4. The concurrent administration of oral Eurartesim with 7.5 mg oral midazolam, a CYP3A4 probe substrate, led to a modest increase (≤2-fold) in midazolam and its metabolites exposures in healthy adult subjects. This inhibitory effect was no longer evident one week after last administration of Eurartesim. Therefore, particular attention should be paid when medicinal products that have a narrow therapeutic index (e.g. antiretroviral medicinal products and cyclosporine) are co-administered with Eurartesim. 21 From in vitro data, piperaquine undergoes a low level of metabolism by CYP2C19, and is also an inhibitor of this enzyme. There is the potential for reducing the rate of metabolism of other substrates of this enzyme, such as omeprazole, with consequent increase of their plasma concentration, and therefore, of their 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): cyclosporine (HOS-084512) midazolam (HOS-086167) omeprazole (HOS-085912)

Wechselwirkungen · Eurartesim

Eurartesim 320 mg/40 mg film-coated tablets. · Abschnitt 4.5 · PDF-Seite 22

HOS-123068 · Präparat HOS-095623

Piperaquine has the potential to increase the rate of metabolism for CYP2E1 substrates resulting in a decrease in the plasma concentrations of substrates such as paracetamol or theophylline, and the anaesthetic gases enflurane, halothane and isoflurane. The main consequence of this interaction could be a reduction of efficacy of the co-administered 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): theophylline (HOS-085910) halothane (HOS-087777) isoflurane (HOS-109378) enflurane (HOS-123023)

Wechselwirkungen · Eurartesim

Eurartesim 320 mg/40 mg film-coated tablets. · Abschnitt 4.5 · PDF-Seite 22

HOS-123069 · Präparat HOS-095623

Artenimol administration may result in a slight decrease in CYP1A2 activity. Caution is therefore, advised when Eurartesim is administered concomitantly with medicinal products metabolised by this enzyme that have a narrow therapeutic index, such as theophylline. Any effects are unlikely to persist beyond 24 hours after the last intake of artenimol.

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): theophylline (HOS-085910)

Wechselwirkungen · Eurartesim

Eurartesim 320 mg/40 mg film-coated tablets. · Abschnitt 4.5 · PDF-Seite 22

HOS-123070 · Präparat HOS-095623

Effect of co-administered medicinal products on Eurartesim Piperaquine is metabolised by CYP3A4 in vitro. The concurrent administration of a single dose of oral clarithromycin, (a strong CYP3A4 inhibitor probe) with a single dose of oral Eurartesim led to a modest increase (≤2-fold) in piperaquine exposure in healthy adult subjects. This increase in exposure to the antimalarial combination may result in an exacerbation of the effect on QTc (see section 4.4). Therefore, particular caution is required if Eurartesim is administered to patients taking potent CYP3A4 inhibitors (e.g. some HIV-protease inhibitors [atazanavir, darunavir, indinavir, lopinavir, ritonavir], or verapamil and ECG monitoring should be considered due to the risk of higher plasma concentrations of piperaquine (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): indinavir (HOS-084518) lopinavir (HOS-086269) atazanavir (HOS-086180) protease (HOS-085623) clarithromycin (HOS-084517) darunavir (HOS-086181) ritonavir (HOS-084521) verapamil (HOS-090602)

Wechselwirkungen · Eurartesim

Eurartesim 320 mg/40 mg film-coated tablets. · Abschnitt 4.5 · PDF-Seite 22

HOS-123071 · Präparat HOS-095623

Enzyme inducing medicinal products such as rifampicin, carbamazepine, phenytoin, phenobarbital, St. John’s wort (Hypericum perforatum) are likely to lead to reduced piperaquine plasma concentrations. The concentration of artenimol may also be reduced.

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) lead (HOS-085592) phenytoin (HOS-084531)

Wechselwirkungen · Eurartesim

Eurartesim 320 mg/40 mg film-coated tablets. · Abschnitt 4.5 · PDF-Seite 22

HOS-123072 · Präparat HOS-095623

When co-administered with efavirenz, the plasma concentration of piperaquine was decreased by 43%. Reduced plasma concentrations of piperaquine and/or artenimol may lead to therapeutic failure. Therefore, concomitant treatment with such medicinal products is not recommended.

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): lead (HOS-085592) efavirenz (HOS-087947)

Wechselwirkungen · Eurartesim

Eurartesim 320 mg/40 mg film-coated tablets. · Abschnitt 4.5 · PDF-Seite 22

HOS-123073 · Präparat HOS-095623

Paediatric population Drug-drug interaction studies have only been performed in adults. The extent of interactions in the paediatric population is not known. The above mentioned interactions for adults and the warnings in section 4.4 should be taken into account for the paediatric population.

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

Wechselwirkungen · Eurartesim

Eurartesim 320 mg/40 mg film-coated tablets. · Abschnitt 4.5 · PDF-Seite 22

HOS-123074 · Präparat HOS-095623

Oral contraceptives When co-administered to healthy women, Eurartesim exerted only a minimum effect on an estrogen/progestinic combination oral contraceptive treatment increasing the ethynilestradiol rate of absorption (expressed by geometric mean Cmax) of about 28% but not significantly changing the exposure to ethynilestradiol and levonorgestrel and not influencing contraception activity as demonstrated by the similar plasma concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH) and progesterone observed after oral contraceptive treatment with or without concomitant Eurartesim 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): progesterone (HOS-090753) follicle stimulating hormone (HOS-123034) levonorgestrel (HOS-089677)

Wechselwirkungen · Eurartesim

Eurartesim 320 mg/40 mg film-coated tablets. · Abschnitt 4.5 · PDF-Seite 22

HOS-123075 · Präparat HOS-095623

Food interaction Absorption of piperaquine is increased in the presence of fatty food (see sections 4.4 and 5.2) which may increase its effect on QTc interval. Therefore, Eurartesim should be taken with water only as described in section 4.2. Eurartesim should not be taken with grapefruit juice as it is likely to lead to increased piperaquine plasma 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): grapefruit juice (HOS-088787) lead (HOS-085592) water (HOS-114523)

Nebenwirkungen · Eurartesim

Eurartesim 160 mg/20 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 8

HOS-123038 · Präparat HOS-095623

Summary of the safety profile The safety of Eurartesim has been evaluated in two phase III open-label studies involving 1,239 paediatric patients up to 18 years and 566 adult patients >18 years treated with Eurartesim.

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

Nebenwirkungen · Eurartesim

Eurartesim 160 mg/20 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 8

HOS-123039 · Präparat HOS-095623

In a randomised trial in which 767 adults and children with uncomplicated P. falciparum malaria were exposed to Eurartesim, 25% of subjects were judged to have experienced an adverse drug reaction (ADR). No single type of ADR occurred at an incidence of ≥5%. The most frequent ADRs observed at an incidence ≥1.0% were: Headache (3.9%), Electrocardiogram QTc Prolonged (3.4%), P. falciparum infection (3.0%), Anaemia (2.8%), Eosinophilia (1.7%), Haemoglobin decreased (1.7%), Sinus tachycardia (1.7%), Asthenia (1.6%), Haematocrit [decreased] (1.6%), Pyrexia (1.5%), Red Blood Cell Count decreased (1.4%). A total of 6 (0.8%) subjects had serious ADRs in the study.

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

Nebenwirkungen · Eurartesim

Eurartesim 160 mg/20 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 8

HOS-123040 · Präparat HOS-095623

In a second randomised trial, 1,038 children, aged between 6 months and 5 years, were exposed to Eurartesim and 71% were judged to have experienced an ADR. The following ADRs were observed at an incidence of ≥5.0%: Cough (32%), Pyrexia (22.4%), Influenza (16.0%), P. falciparum infection (14.1%), Diarrhoea (9.4%), Vomiting (5.5%) and Anorexia (5.2%). A total of 15 (1.5%) subjects had serious ADRs in the study.

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

Nebenwirkungen · Eurartesim

Eurartesim 160 mg/20 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 8

HOS-123041 · Präparat HOS-095623

Tabulated list of adverse reactions In the tables below, ADRs are listed under system organ class (SOC), and ranked by headings of frequency. Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness, 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

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

Nebenwirkungen · Eurartesim

Eurartesim 160 mg/20 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 8–9

HOS-123042 · Präparat HOS-095623

8 (cannot be estimated from the available data). The table in this section is for adult patients only. A corresponding table for paediatric patients is presented in the specific section below.

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

Nebenwirkungen · Eurartesim

Eurartesim 160 mg/20 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 9

HOS-123043 · Präparat HOS-095623

Frequency of ADRs in adult patients participating in clinical studies with Eurartesim and post- marketing data:

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

Nebenwirkungen · Eurartesim

Eurartesim 160 mg/20 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 9

HOS-123044 · Präparat HOS-095623

Very SOC Common Uncommon Not known Common Respiratory tract Infections and P. falciparum infection infestations infection Influenza Autoimmune Blood and haemolytic anaemia lymphatic Anaemia Delayed haemolytic system disorders anaemia Metabolism and nutrition Anorexia disorders Nervous system Convulsion Headache disorders Dizziness Cardiac conduction QTc disorders Cardiac disorders prolonged Sinus arrhythmias Tachycardia Bradycardia Respiratory, thoracic Cough and mediastinal disorders Vomiting Gastrointestinal Diarrhoea disorders Nausea Abdominal pain Hepatitis Hepatocellular injury Hepatobiliary Hepatomegaly disorders Abnormal liver function tests Skin and subcutaneous Pruritis Tissue disorders Musculoskeletal and Arthralgia connective tissue Myalgia disorders General disorders and Asthenia administration site Pyrexia conditions

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

Nebenwirkungen · Eurartesim

Eurartesim 160 mg/20 mg film-coated tablets. · Abschnitt 4.8 · PDF-Seite 9

HOS-123045 · Präparat HOS-095623

Description of selected adverse reactions The ADRs noted for Eurartesim were generally mild in severity, and the majority were non-serious. Reactions such as cough, pyrexia, headache, P. falciparum infection, anaemia, asthenia, anorexia and the observed changes in blood cell parameters are consistent with those expected in patients with acute

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