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Zydelig is a brand name for Idelalisib. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Zydelig is indicated in combination with rituximab for the treatment of adult patients with chronic lymphocytic leukaemia (CLL): • who have received at least one prior therapy (see section 4.4), or • as first line treatment in the presence of 17p deletion or TP53 mutation in patients who are not eligible for any other…
Verbatim from this product's EMA label. Tap a section to expand.
Treatment with Zydelig should be conducted by a physician experienced in the use of anti-cancer therapies. 3 Posology The recommended dose is 150 mg idelalisib twice daily. Treatment should be continued until disease progression or unacceptable toxicity.
If the patient misses a dose of Zydelig within 6 hours of the time it is usually taken, the patient should take the missed dose as soon as possible and resume the normal dosing schedule. If a patient misses a dose by more than 6 hours, the patient should not take the missed dose and simply resume the usual dosing schedule.
Dose modification Elevated liver transaminases Treatment with Zydelig must be withheld in the event of a Grade 3 or 4 aminotransferase elevation (alanine aminotransferase [ALT]/aspartate aminotransferase [AST] > 5 x upper limit of normal [ULN]).
Once values have returned to Grade 1 or below (ALT/AST ≤ 3 x ULN), treatment can be resumed at 100 mg twice daily. If the event does not recur, the dose can be re-escalated to 150 mg twice daily at the discretion of the treating physician.
8). Diarrhoea/colitis Treatment with Zydelig must be withheld in the event of Grade 3 or 4 diarrhoea/colitis. Once diarrhoea/colitis has returned to Grade 1 or below, treatment can be resumed at 100 mg twice daily. 8). Pneumonitis Treatment with Zydelig must be withheld in the event of suspected pneumonitis.
Once pneumonitis has resolved and if re-treatment is appropriate, resumption of treatment at 100 mg twice daily can be considered. 8). Rash Treatment with Zydelig must be withheld in the event of Grade 3 or 4 rash. Once rash has returned to Grade 1 or below, treatment can be resumed at 100 mg twice daily.
8). Neutropenia Treatment with Zydelig should be withheld in patients while absolute neutrophil count (ANC) is below 500 per mm3. 4). ANC 1 000 to < 1 500/mm3 ANC 500 to < 1 000/mm3 ANC < 500/mm3 Maintain Zydelig dosing. Maintain Zydelig dosing.
Monitor ANC at least weekly. Interrupt Zydelig dosing. Monitor ANC at least weekly until ANC ≥ 500/mm3, then may resume Zydelig dosing at 100 mg twice daily. 2). 2). 2). There is insufficient data to make dose recommendations for patients with severe hepatic impairment.
2). Paediatric population The safety and efficacy of Zydelig in children under the age of 18 years have not been established. No data are available. Method of administration Zydelig is for oral use. Patients should be instructed to swallow the tablet whole.
Summary of the safety profile In clinical studies of subjects with hematologic malignancies who received idelalisib, the most frequently reported adverse reactions were: infections (70%), neutropenia (55%), transaminases increased (53%), diarrhoea (48%), triglycerides increased (47%), pyrexia (36%), rash (30%) and lymphocytosis (21%).
The most frequently reported severe adverse reactions (≥ Grade 3) were: infections (39%), neutropenia (33%), diarrhoea/colitis (22%), transaminases increased (15%) and lymphocytosis (13%). Tabulated list of adverse reactions Assessment of adverse reactions is based on two Phase 3 studies (study 312-0116 and study 312-0119) and six Phase 1 and 2 studies.
Study 312-0116 was a randomised, double-blind, placebo-controlled study in which 110 subjects with previously treated CLL received idelalisib + rituximab. In addition, 86 subjects from this study who were randomised to receive placebo + rituximab went on to receive idelalisib as a single agent in an extension study (study 312-0117).
Study 312-0119 was a randomised, controlled, open-label study in which 173 subjects with previously treated CLL received idelalisib + ofatumumab. The Phase 1 and 2 studies assessed the safety of idelalisib in a total of 536 subjects with haematologic malignancies, including 400 subjects who received idelalisib (any dose) as a single agent 12 and 136 subjects who received idelalisib in combination with an anti-CD20 monoclonal antibody (rituximab or ofatumumab).
The adverse drug reactions reported with idelalisib alone or in combination with anti-CD20 monoclonal antibodies (rituximab or ofatumumab) are provided in Table 2. Adverse reactions are listed by system organ class and frequency. 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), and not known (cannot be estimated from available data).
Serious infections Treatment with Zydelig should not be initiated in patients with any evidence of ongoing systemic bacterial, fungal, or viral infection. Serious and fatal infections have occurred with idelalisib, including opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP) and cytomegalovirus (CMV).
Prophylaxis for PJP should therefore be administered to all patients throughout idelalisib treatment, and for a period of 2 to 6 months after discontinuation. 8). Patients should be monitored for respiratory signs and symptoms throughout treatment.
Patients should be advised to report new respiratory symptoms promptly. Regular clinical and laboratory monitoring for CMV infection is recommended in patients with positive CMV serology at the start of treatment with idelalisib or with other evidence of a history of CMV infection.
Patients with CMV viraemia without associated clinical signs of CMV infection should be carefully monitored. For patients with evidence of CMV viraemia and clinical signs of CMV infection, consideration should be given to interrupting idelalisib until the infection has resolved.
If the benefits of resuming idelalisib are judged to outweigh the risks, consideration should be given to administering pre-emptive CMV therapy. 5 Cases of progressive multifocal leukoencephalopathy (PML) have been reported following the use of idelalisib within the context of prior or concomitant immunosuppressive therapies that have been associated with PML.
Physicians should consider PML in the differential diagnosis in patients with new or worsening neurological, cognitive or behavioural signs or symptoms. If PML is suspected then appropriate diagnostic evaluations should be undertaken and treatment suspended until PML is excluded.
If any doubt exists, referral to a neurologist and appropriate diagnostic measures for PML including MRI scan preferably with contrast, cerebrospinal fluid (CSF) testing for JC viral DNA and repeat neurological assessments should be considered.
1.
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The film-coated tablet should not be chewed or crushed. 2).
Table 2:
Adverse drug reactions reported in clinical studies in subjects with haematologic malignancies receiving idelalisib and post-marketing. Reaction Any grade Grade ≥ 3 Infections and infestations Infections (including Pneumocystis jirovecii pneumonia and CMV)* Very common Very common Blood and lymphatic system disorders Neutropenia Very common Very common Lymphocytosis** Very common Very common Respiratory, thoracic and mediastinal disorders Pneumonitis Common Common Organising pneumonia**** Uncommon Uncommon Gastrointestinal disorders Diarrhoea/colitis Very common Very common Hepatobiliary disorders Transaminase increased Very common Very common Hepatocellular injury Common Common Skin and subcutaneous tissue disorders Rash*** Very common Common Stevens-Johnson syndrome/ toxic epidermal necrolysis**** Rare Rare Drug reaction with eosinophilia and systemic symptoms (DRESS)**** Not known Not known General disorders and administration site conditions Pyrexia Very common Common Investigations Increased triglycerides Very common Common * Comprised of opportunistic infections as well as bacterial and viral infections such as pneumonia, bronchitis, and sepsis.
1). *** Includes the preferred terms dermatitis exfoliative generalised, drug eruption, rash, rash erythematous, rash generalised, rash macular, rash maculo-papular, rash papular, rash pruritic, rash pustular, rash vesicular, papule, skin plaque, and exfoliative rash.
4) Higher frequencies of infections overall, including Grade 3 and 4 infections, were observed in the idelalisib arms compared to the control arms of idelalisib clinical studies. Most frequently observed were infections in the respiratory system and septic events.
In many instances the pathogen was not identified; however, both conventional and opportunistic pathogens, including PJP and CMV, were among those identified. Nearly all PJP infections, including fatal cases, occurred in the absence of PJP prophylaxis.
There have been cases of PJP after stopping idelalisib treatment. 1% of subjects. 2% who received an anti-CD20 monoclonal antibody only (rituximab or ofatumumab). 5% who received an anti-CD20 monoclonal antibody only (rituximab or ofatumumab) had rash of Grade 3, and no subjects had an adverse reaction of Grade 4.
3, phototoxicity). 4) Cases of SJS, TEN and DRESS have occurred when idelalisib was administered concomitantly with other medicinal products associated with these syndromes (bendamustine, rituximab, allopurinol, amoxicillin, and sulfamethoxazole / trimethoprim).
SJS or TEN occurred within one month of the medicinal combination and fatal outcomes have resulted. 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.
Neutropenia Treatment-emergent Grade 3 or 4 neutropenia, including febrile neutropenia, have occurred in patients treated with idelalisib. 2). Hepatotoxicity Elevations in ALT and AST of Grade 3 and 4 (> 5 x ULN) have been observed in clinical studies of idelalisib.
There have also been reports of hepatocellular injury including hepatic failure. 2). In patients who resumed idelalisib at a lower dose, 26% had recurrence of ALT/AST elevation. Treatment with Zydelig must be withheld in the event of Grade 3 or 4 ALT/AST elevation and liver function monitored.
Treatment may be resumed at a lower dose once values have returned to Grade 1 or below (ALT/AST ≤ 3 x ULN). ALT, AST, and total bilirubin must be monitored in all patients every 2 weeks for the first 3 months of treatment, then as clinically indicated.
If Grade 2 or higher elevations in ALT and/or AST are observed, patients’ ALT, AST, and total bilirubin must be monitored weekly until the values return to Grade 1 or below. Hepatic impairment Intensified monitoring of adverse reactions is recommended in patients with impaired hepatic function as exposure is expected to be increased in this population, in particular in patients with severe hepatic impairment.
No patients with severe hepatic impairment were included in clinical studies of idelalisib. Caution is recommended when administering Zydelig in this population. Chronic hepatitis Idelalisib has not been studied in patients with chronic active hepatitis including viral hepatitis.
Caution should be exercised when administering Zydelig in patients with active hepatitis. 2). There is very limited experience from the treatment of patients with a history of inflammatory bowel disease. 6 Pneumonitis and organising pneumonia Cases of pneumonitis and organising pneumonia (some with fatal outcome) have been reported with idelalisib.
In patients presenting with serious lung events, idelalisib should be interrupted and the patient assessed for an explanatory aetiology. If either moderate or severe symptomatic pneumonitis or organising pneumonia is diagnosed, appropriate treatment should be initiated and idelalisib must be permanently discontinued.
Severe cutaneous reactions Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) have occurred with idelalisib. Cases of SJS and TEN with fatal outcomes have been reported when idelalisib was administered concomitantly with other medicinal products associated with these syndromes.
If SJS, TEN or DRESS is suspected, idelalisib should be interrupted and the patient assessed and treated accordingly. If a diagnosis of SJS, TEN, or DRESS is confirmed, idelalisib should be permanently discontinued. CYP3A inducers Idelalisib exposure may be reduced when co-administered with CYP3A inducers such as rifampicin, phenytoin, St.
John’s wort (Hypericum perforatum), or carbamazepine. Since a reduction in idelalisib plasma concentrations may result in decreased efficacy, co-administration of Zydelig with moderate or strong […]