Wirkstoffe & Arzneimittelsicherheit

Nebenwirkungen · Litak

LITAK 2 mg/ml solution for injection · Abschnitt 4.8 · PDF-Seite 6

HOS-112295 · Präparat HOS-093643

Tabulated list of adverse reactions Adverse reactions that have been reported are listed in the table below by frequency category and system organ class. The frequencies are defined as follows: 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). For severity, please see text below the table.

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

Nebenwirkungen · Litak

LITAK 2 mg/ml solution for injection · Abschnitt 4.8 · PDF-Seite 6–7

HOS-112296 · Präparat HOS-093643

6 Infections and infestations Very common: infections * (e.g. pneumonia *, septicaemia *) Neoplasms benign, malignant Common: second malignancies * and unspecified (incl cysts and Rare: tumour lysis syndrome * polyps) Blood and lymphatic system Very common: pancytopenia/myelosuppression *, neutropenia, disorders thrombocytopenia, anemia, lymphopenia Uncommon: haemolytic anaemia * Rare: hypereosinophilia Very rare: amyloidosis Immune system disorders Very common: immunosuppression * Rare: graft-versus-host disease * Metabolism and nutrition Very common: decreased appetite disorders Uncommon: cachexia Nervous system disorders Very common: headache, dizziness Common: insomnia, anxiety Uncommon: somnolence, paraesthesia, lethargy, polyneuropathy, confusion, ataxia Rare: apoplexy, neurological disturbances in speech and swallowing Very rare: depression, epileptic seizure Eye disorders Uncommon: conjunctivitis Very rare: blepharitis Cardiac disorders Common: tachycardia, heart murmur, hypotension, epistaxis, myocardial ischemia * Rare: Cardiac failure, atrial fibrillation, cardiac decompensation Vascular disorders Very common: purpura Common: petechiae, haemorrhages * Uncommon: phlebitis Respiratory, thoracic and Very common: abnormal breath sounds, abnormal chest sounds, mediastinal disorders cough Common: shortness of breath, pulmonary interstitial infiltrates mostly due to infectious aetiology, mucositis Uncommon: pharyngitis Very rare: lung embolism Gastrointestinal disorders Very common: nausea, vomiting, constipation, diarrhoea Common: gastrointestinal pain, flatulence Rare: ileus Hepato-biliary disorders Common: reversible, mostly mild increases in bilirubin and transaminases Rare: hepatic failure Very rare: cholecystitis Skin and subcutaneous tissue Very common: rash, localised exanthema, diaphoresis disorders Common: pruritus, skin pain, erythema, urticaria Rare: Stevens-Johnson syndrome/Lyell syndrome Musculoskeletal and connective Common: myalgia, arthralgia, arthritis, bone pain tissue disorders Renal and urinary disorders Rare: renal failure General disorders and Very common: injection site reactions, fever, fatigue, chills, administration site conditions asthenia Common: oedema, malaise, pain * see descriptive section below.

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

Nebenwirkungen · Litak

LITAK 2 mg/ml solution for injection · Abschnitt 4.8 · PDF-Seite 7–8

HOS-112297 · Präparat HOS-093643

7 Description of selected adverse reactions Non-haematological adverse reactions Non-haematological adverse reactions are generally mild to moderate in severity. Treatment of nausea with antiemetics is usually not necessary. Adverse reactions related to skin and subcutaneous tissue are mostly mild or moderate and transient, usually resolving within a cycle interval of 30 days.

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

Nebenwirkungen · Litak

LITAK 2 mg/ml solution for injection · Abschnitt 4.8 · PDF-Seite 8

HOS-112298 · Präparat HOS-093643

Blood counts Since patients with an active hairy cell leukaemia mostly present with low blood counts, especially low neutrophil counts, more than 90% of the cases have transient severe neutropenias (< 1.0 x 109/l). The use of haematopoietic growth factors neither improves the recovery of neutrophil counts nor decreases the incidence of fever. Severe thrombocytopenias (< 50 x 109/l) are observed in about 20% to 30% of all patients. Lymphocytopenia lasting for several months and immunosuppression with an increased risk of infections are expected. The recovery of cytotoxic T-lymphocytes and natural killer cells occurs within 3 to 12 months. A complete recovery of T-helper cells and B-lymphocytes is delayed for up to 2 years. Cladribine induces a severe and prolonged reduction of CD4+ and CD8+ T-lymphocytes. At present there exists no experience on possible long-term consequences of this immunosuppression.

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

Nebenwirkungen · Litak

LITAK 2 mg/ml solution for injection · Abschnitt 4.8 · PDF-Seite 8

HOS-112299 · Präparat HOS-093643

Infections Severe long-term lymphocytopenias have been reported rarely which, however, could not be associated with late infectious complications. Very common severe complications, in some cases with fatal outcome, are opportunistic infections (e.g. Pneumocystis carinii, Toxoplasma gondii, listeria, candida, herpes viruses, cytomegalovirus and atypical mycobacteria). Forty percent of the patients who were treated with LITAK at a dose of 0.7 mg/kg body weight per cycle suffered from infections. These were on average more severe than the infections manifested in 27% of all patients receiving a reduced dose of 0.5 mg/kg body weight per cycle. Forty-three percent of patients with hairy cell leukaemia experienced infectious complications at standard dose regimen. One third of these infections have to be considered as severe (e.g. septicaemia, pneumonia). At least 10 cases with acute autoimmune haemolytic anaemia have been reported. All patients were successfully treated with corticosteroids.

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

Nebenwirkungen · Litak

LITAK 2 mg/ml solution for injection · Abschnitt 4.8 · PDF-Seite 8

HOS-112300 · Präparat HOS-093643

Rare serious adverse reactions Serious adverse reactions like ileus, severe hepatic failure, renal failure, cardiac failure, atrial fibrillation, cardiac decompensation, apoplexy, neurological disturbances in speech and swallowing, tumour lysis syndrome with acute renal failure, transfusion-related graft-versus-host disease, Stevens-Johnson syndrome/Lyell syndrome (toxic epidermal necrolysis), haemolytic anaemia, hypereosinophilia (with erythematous skin rash, pruritus, and facial oedema) are rare.

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

Nebenwirkungen · Litak

LITAK 2 mg/ml solution for injection · Abschnitt 4.8 · PDF-Seite 8

HOS-112301 · Präparat HOS-093643

Fatal outcome The majority of deaths related to the medicinal product are due to infectious complications. Further rare cases with fatal outcome, reported in association with LITAK chemotherapy, were second malignancy, cerebro- and cardiovascular infarctions, graft-versus-host disease caused by multiple transfusions of non-irradiated blood, as well as tumour lysis syndrome with hyperuricaemia, metabolic acidosis, and acute renal failure.

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

Nebenwirkungen · Litak

LITAK 2 mg/ml solution for injection · Abschnitt 4.8 · PDF-Seite 8

HOS-112302 · Präparat HOS-093643

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 · Kivexa

Kivexa 600 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 9

HOS-113481 · Präparat HOS-093937

Clinically significant interaction unlikely. Cimetidine eliminated only in part by renal organic cation transport system. CYTOTOXICS Cladribine/Lamivudine Interaction not studied. Therefore, the concomitant use of lamivudine with cladribine In vitro lamivudine inhibits the is not recommended (see intracellular phosphorylation of section 4.4). cladribine leading to a potential risk of cladribine loss of efficacy in case of combination in the clinical setting. Some clinical findings also support a possible interaction between lamivudine and cladribine OPIOIDS Methadone/Abacavir Abacavir: AUC  No Kivexa dosage adjustment (40 to 90 mg once daily for 14 Cmax 35% necessary. days/600 mg single dose, then 600 mg twice daily for 14 days) Methadone: CL/F 22% Methadone dosage adjustment unlikely in majority of Methadone/Lamivudine Interaction not studied. patients; occasionally methadone re-titration may be required.

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): methadone (HOS-086198) cimetidine (HOS-085835) cladribine (HOS-085842)

Wechselwirkungen · Lamivudine Teva Pharma B.V.

Lamivudine Teva Pharma B.V. 150 mg film-coated tablets Lamivudine Teva Pharma B.V. 300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 6

HOS-211910 · Präparat HOS-154784

In vitro lamivudine inhibits the intracellular phosphorylation of cladribine leading to a potential risk of cladribine loss of efficacy in case of combination in the clinical setting. Some clinical findings also support a possible interaction between lamivudine and cladribine. Therefore, the concomitant use of lamivudine with cladribine is not recommended (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): cladribine (HOS-085842)

Wechselwirkungen · Lamivudine Teva

Lamivudine Teva 100 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 6

HOS-211996 · Präparat HOS-154800

Cladribine In vitro lamivudine inhibits the intracellular phosphorylation of cladribine leading to a potential risk of cladribine loss of efficacy in case of combination in the clinical setting. Some clinical findings also support a possible interaction between lamivudine and cladribine. Therefore, the concomitant use of lamivudine with cladribine is not recommended (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): cladribine (HOS-085842)

Wechselwirkungen · Triumeq

Triumeq 50 mg/600 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12

HOS-129267 · Präparat HOS-096703

Clinically significant interaction unlikely. Cytotoxics Cladribine/Lamivudine Interaction not studied. Concomitant use of Triumeq with cladribine is not recommended (see In vitro lamivudine section 4.4). inhibits the intracellular

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): cladribine (HOS-085842)

Wechselwirkungen · Triumeq

Triumeq 50 mg/600 mg/300 mg film-coated tablets · Abschnitt 4.5 · PDF-Seite 12–13

HOS-129269 · Präparat HOS-096703

12  phosphorylation of cladribine leading to a potential risk of cladribine loss of efficacy in case of combination in the clinical setting. Some clinical findings also support a possible interaction between lamivudine and cladribine Opioids Methadone/Abacavir Abacavir: Methadone dose adjustment likely not (40 to 90mg once daily for 14 AUC ↔ needed in majority of patients; days/600mg single dose, then Cmax ↓35% occasionally methadone re-titration may 600mg twice daily for 14 days) be required. Methadone: CL/F ↑22% Retinoids Retinoid compounds Interaction not studied Insufficient data to recommend dose (e.g. Isotretinoin) adjustment. Possible interaction given common pathway of elimination via alcohol dehydrogenase (abacavir- component). Miscellaneous Alcohol Ethanol/Dolutegravir Interaction not studied No dose adjustment necessary. Ethanol/Lamivudine (Inhibition of alcohol dehydrogenase)

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): methadone (HOS-086198) isotretinoin (HOS-108570) ethanol (HOS-089988) cladribine (HOS-085842)

Wechselwirkungen · Triumeq

Triumeq 5 mg/60 mg/30 mg dispersible tablets · Abschnitt 4.5 · PDF-Seite 49

HOS-129360 · Präparat HOS-096703

Clinically significant interaction unlikely. Cytotoxics Cladribine/Lamivudine Interaction not studied. Concomitant use of Triumeq with cladribine is not recommended (see In vitro lamivudine section 4.4). inhibits the intracellular phosphorylation of cladribine leading to a potential risk of cladribine loss of efficacy in case of combination in the clinical setting. Some clinical findings also support a possible interaction between lamivudine and cladribine Opioids Methadone/Abacavir Abacavir: Methadone dose adjustment likely not (40 to 90mg once daily for 14 AUC ↔ needed in majority of patients; days/600mg single dose, then Cmax ↓35% occasionally methadone re-titration may 600mg twice daily for 14 days) be required. Methadone: CL/F ↑22%

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): methadone (HOS-086198) cladribine (HOS-085842)

Gegenanzeigen · Mavenclad

MAVENCLAD 10 mg tablets · Abschnitt 4.3 · PDF-Seite 4

HOS-136664 · Präparat HOS-097904

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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

Gegenanzeigen · Mavenclad

MAVENCLAD 10 mg tablets · Abschnitt 4.3 · PDF-Seite 4

HOS-136665 · Präparat HOS-097904

Infection with human immunodeficiency virus (HIV).

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

Gegenanzeigen · Mavenclad

MAVENCLAD 10 mg tablets · Abschnitt 4.3 · PDF-Seite 4

HOS-136666 · Präparat HOS-097904

Active chronic infection (tuberculosis or hepatitis).

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

Gegenanzeigen · Mavenclad

MAVENCLAD 10 mg tablets · Abschnitt 4.3 · PDF-Seite 4

HOS-136667 · Präparat HOS-097904

Initiation of cladribine treatment in immunocompromised patients, including patients currently receiving immunosuppressive or myelosuppressive therapy (see section 4.5).

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

Gegenanzeigen · Mavenclad

MAVENCLAD 10 mg tablets · Abschnitt 4.3 · PDF-Seite 4

HOS-136668 · Präparat HOS-097904

Active malignancy.

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

Gegenanzeigen · Mavenclad

MAVENCLAD 10 mg tablets · Abschnitt 4.3 · PDF-Seite 4

HOS-136669 · Präparat HOS-097904

Moderate or severe renal impairment (creatinine clearance <60 mL/min) (see section 5.2).

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): creatinine (HOS-086273)