Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Litak

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HOS-112279 · Präparat HOS-093643

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

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Gegenanzeigen · Litak

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HOS-112280 · Präparat HOS-093643

Pregnancy and lactation.

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Gegenanzeigen · Litak

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HOS-112281 · Präparat HOS-093643

Patients less than 18 years of age.

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Gegenanzeigen · Litak

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HOS-112282 · Präparat HOS-093643

Moderate to severe renal impairment (creatinine clearance ≤ 50 ml/min) or moderate to severe hepatic impairment (Child-Pugh score > 6) (see also section 4.4).

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): creatinine (HOS-086273)

Gegenanzeigen · Litak

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HOS-112283 · Präparat HOS-093643

Concomitant use of other myelosuppressive medicinal products.

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Wechselwirkungen · Litak

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HOS-112284 · Präparat HOS-093643

Due to a potential increase of haematological toxicity and bone marrow suppression, cladribine must not be used concomitantly with other myelosuppressive medicinal products. An influence of cladribine on the activity of other antineoplastic agents has not been observed in vitro (e.g. doxorubicin, vincristine, cytarabine, cyclophosphamide) and in vivo. However, an in vitro study revealed cross-resistance between cladribine and nitrogen mustard (chlormethine); for cytarabine, one author has described an in vivo cross-reaction without loss of activity.

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): cytarabine (HOS-112286) vincristine (HOS-086219) nitrogen (HOS-108524) cyclophosphamide (HOS-084539) doxorubicin (HOS-084538)

Wechselwirkungen · Litak

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HOS-112288 · Präparat HOS-093643

Due to the similar intracellular metabolism, cross-resistance with other nucleoside analogues, such as fludarabine or 2’-deoxycoformycin may occur. Therefore, simultaneous administration of nucleoside analogues with cladribine is not advisable.

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): fludarabine (HOS-087520)

Wechselwirkungen · Litak

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HOS-112290 · Präparat HOS-093643

Corticosteroids have been shown to enhance the risk for severe infections when used in combination with cladribine and should not be given concomitantly with cladribine.

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Wechselwirkungen · Litak

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HOS-112291 · Präparat HOS-093643

Since interactions with medicinal products undergoing intracellular phosphorylation, such as antiviral agents, or with inhibitors of adenosine uptake may be expected, their concomitant use with cladribine is not recommended.

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RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): adenosine (HOS-112292)

Nebenwirkungen · Litak

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HOS-112293 · Präparat HOS-093643

Summary of the safety profile Very common adverse reactions observed during the three most relevant clinical trials with cladribine in 279 patients treated for various indications and in 62 patients with hairy cell leukaemia (HCL) were myelosuppression, especially severe neutropenia (41% (113/279), HCL 98% (61/62)), severe thrombocytopenia (21% (58/279), HCL 50% (31/62)) and severe anaemia (14% (21/150), HCL 55% (34/62)), as well as severe immunosuppression/lymphopenia (63% (176/279), HCL 95% (59/62)), infections (39% (110/279), HCL 58% (36/62)) and fever (up to 64%).

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Nebenwirkungen · Litak

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HOS-112294 · Präparat HOS-093643

Culture-negative fever following treatment with cladribine occurs in 10-40% of patients with hairy cell leukaemia and is rarely observed in patients with other neoplastic disorders. Skin rashes (2-31%) are mainly described in patients with other concomitantly administered medicinal products known to cause rash (antibiotics and/or allopurinol). Gastrointestinal adverse reactions like nausea (5-28%), vomiting (1-13%), and diarrhoea (3-12%) as well as fatigue (2-48%), headache (1-23%), and decreased appetite (1-22%) have been reported during treatment with cladribine. Cladribine is unlikely to cause alopecia; mild and transient alopecia for a few days was observed in 4/523 patients during the treatment, but could not clearly be associated with cladribine.

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Nebenwirkungen · Litak

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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.

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Nebenwirkungen · Litak

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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.

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Nebenwirkungen · Litak

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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.

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Nebenwirkungen · Litak

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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.

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Nebenwirkungen · Litak

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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.

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Nebenwirkungen · Litak

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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.

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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.

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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.

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